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With the objective to investigate associations between sociodemographic characteristics and participation in interventions designed to increase participation in cervical cancer screening among under-screened women, we randomized a random sample of 6000 women in Norway aged 35-69 years who had not attended cervical screening for ≥10 years to receive either (i) a reminder to attend regular screening (control), (ii) an offer to order a self-sampling kit (opt-in), or (iii) a self-sampling kit unsolicited (send-to-all). We analyzed how sociodemographic characteristics were associated with screening participation within and between screening arms. In the send-to-all arm, increased screening participation ranged from 17.1% (95% confidence interval [95% CI] = 10.3% to 23.8%) to 30.0% (95% CI = 21.5% to 38.6%) between sociodemographic groups. In the opt-in arm, we observed smaller, and at times, non-significant increases within the range 0.7% (95% CI = -5.8% to 7.3%) to 19.1% (95% CI = 11.6% to 26.7%). In send-to-all versus control comparisons, there was greater increase in participation for women in the workforce versus not (6.1%, 95% CI = 1.6% to 10.6%), with higher versus lower income (7.6%, 95% CI = 2.2% to 13.1%), and with university versus primary education (8.5%, 95% CI = 2.4% to 14.6%). In opt-in versus control comparisons, there was greater increase in participation for women in the workforce versus not (4.6%, 95% CI = 0.7% to 8.5%), with higher versus lower income (6.3%, 95% CI = 1.5% to 11.1%), but lower increase for Eastern European versus Norwegian background (-12.7%, 95% CI = -19.7% to -5.7%). Self-sampling increased cervical screening participation across all sociodemographic levels, but inequalities in participation should be considered when introducing self-sampling, especially with the goal to reach long-term non-attending women., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Endocervical adenocarcinomas (EACs) are a group of malignant neoplasms associated with diverse pathogenesis, morphology, and clinical behavior. As a component of the International Society of Gynecological Pathologists International Endocervical Adenocarcinoma Project, a large international retrospective cohort of EACs was generated in an effort to study potential clinicopathological features with prognostic significance that may guide treatment in these patients. In this study, we endeavored to develop a robust human papillomavirus (HPV)-associated EAC prognostic model for surgically treated International Federation of Gynecology and Obstetrics (FIGO) stage IA2 to IB3 adenocarcinomas incorporating patient age, lymphovascular space invasion (LVSI) status, FIGO stage, and pattern of invasion according to the Silva system (traditionally a 3-tier system). Recently, a 2-tier/binary Silva pattern of invasion system has been proposed whereby adenocarcinomas are classified into low-risk (pattern A/pattern B without LVSI) and high-risk (pattern B with LVSI/pattern C) categories. Our cohort comprised 792 patients with HPV-associated EAC. Multivariate analysis showed that a binary Silva pattern of invasion classification was associated with recurrence-free and disease-specific survival (P < 0.05) whereas FIGO 2018 stage I substages were not. Evaluation of the current 3-tiered system showed that disease-specific survival for those patients with pattern B tumors did not significantly differ from that for those patients with pattern C tumors, in contrast to that for those patients with pattern A tumors. These findings underscore the need for prospective studies to further investigate the prognostic significance of stage I HPV-associated EAC substaging and the inclusion of the binary Silva pattern of invasion classification (which includes LVSI status) as a component of treatment recommendations., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 by the International Society of Gynecological Pathologists.)

Cervical cancer is the fourth most common malignancy in women worldwide. The identification of human papillomavirus (HPV) as the main etiologic cause of cervical cancer has led to the development and adaptation of HPV molecular diagnostics as a cervical cancer screening and prevention tool. This article highlights six Food and Drug Administration-approved HPV molecular platforms, each with unique advantages and disadvantages. In addition, HPV vaccination and the emergence of HPV self-collection as an alternative testing strategy are discussed., Competing Interests: Disclosure The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: In Denmark, where human papillomavirus (HPV) -based cervical cancer screening is being implemented, the aim of this pilot implementation study was to test a specific screening algorithm, assess follow-up examination attendance, and measure the proportion of precancer lesions found in relation to the number of women referred for colposcopy., Material and Methods: From May 2017 to December 2020, 36 417 women in the uptake area of the Department of Pathology, Vejle Hospital, Region of Southern Denmark, were included in the HPV group. Women positive for HPV16/18 irrespective of cytology and women positive for other high-risk HPV (hrHPV) types having concomitant abnormal cytology were referred directly to colposcopy. Women positive for other hrHPV types and normal cytology were referred to repeat screening after 12 months, and hrHPV negative to routine screening after three years. We obtained information on screening results and subsequent histological diagnosis from the Danish Pathology Databank through September 2022., Results: 3.6% of the women were referred to colposcopy after primary screening, 5% to repeat screening after 12 months, and 91.4% back to routine screening. High follow-up rates were observed: 96% attended colposcopy after primary screening, with 91% attending colposcopy after repeat screening. CIN3+ was detected at colposcopy following the primary screening in 28.1% of HPV16/18-positive women and 18.2% of those positive for other hrHPV types with concomitant abnormal cytology. Of the women with other hrHPV and simultaneous ASCUS/LSIL, 8% had CIN3+. At the repeat screening, 43% had become hrHPV negative, 55% were persistently positive for other hrHPV, and 2% had turned positive for HPV16/18. At the colposcopy following repeat screening, 10.1% of the women positive for other hrHPV were diagnosed with CIN3+, in comparison with 11.1% of the HPV16/18-positive women., Conclusions: In this pilot implementation study, an algorithm for HPV-based screening was evaluated in a Danish setting. The results demonstrated high attendance at follow-up examinations and provided insights into the number of colposcopy referrals and the detection of CIN2 and CIN3+ cases. The results suggest that women testing positive for other hrHPV in combination with ASCUS/LSIL at primary screening could potentially be referred to repeat screening instead of an immediate colposcopy., (© 2024 The Author(s). Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Objective: To compare the pelvic lymph node involvement and risk of recurrence in patients with human papillomavirus (HPV)-associated endocervical adenocarcinoma stage IA2-IB1 undergoing hysterectomy and/or trachelectomy plus lymphadenectomy, according to Silva's classification system., Methods: A retrospective cohort study was performed in two Colombian cancer centers. The cases were classified according to the Silva classification system. Clinical, surgical, and histopathological variables were evaluated. Recurrence risk was analyzed by patterns A, B, or C. A logistic regression model was performed for tumor recurrence. The Kaplan-Meier method was used to estimate overall survival and disease-free survival (DFS). A weighted kappa was performed to determine the degree of concordance between pathologists., Results: A total of 100 patients were identified, 33% pattern A, 29% pattern B, and 38% pattern C. The median follow-up time was 42.5 months. No evidence of lymph node involvement was found in patients classified as A and B, while in the C pattern was observed in 15.8% (n = 6) of cases (P < 0.01). There were 7% of cases with recurrent disease, of which 71.5% corresponded to type C pattern. Patients with Silva pattern B and C had 1.22- and 4.46-fold increased risk of relapse, respectively, compared with pattern A. The 5-year DFS values by group were 100%, 96.1%, and 80.3% for patterns A, B, and C, respectively., Conclusion: For patients with early-stage HPV-associated endocervical adenocarcinoma, the type C pattern presented more lymph node involvement and risk of recurrence compared to the A and B patterns. The concordance in diagnosis of different Silva's patterns by independents pathologists were good., (© 2024 International Federation of Gynecology and Obstetrics.)

Competing Interests: The authors declare no conflict of interest.

Small cell neuroendocrine carcinoma (NEC) of the cervix is a rare gynecological malignancy, constituting 2%-5% of all such cases. As high-risk Human Papilloma Virus (HR-HPV) infections contribute to 85% of these tumors, small cell NEC poses a significant risk for solid organ transplant recipients, increasing their risk of progressive disease. We present a case of an uterine cervix small cell NEC with metastasis to the bladder and pleural cavities in a 53-year-old woman with a past medical history of kidney transplantation, who presented with abnormal uterine bleeding. The initial liquid preparation (ThinPrep) cytology stained with Papanicolaou (Pap) showed an adenocarcinoma not otherwise specified. At the time of diagnosis, the patient had diffusely metastatic disease. A subsequent uterine cervix biopsy was consistent with a small cell NEC. Despite treatment with chemotherapy, the patient's condition deteriorated, evidenced by a worsening right-sided pleural effusion one-month postdiagnosis. A pleural effusion showed a tumor with glandular features, with immunohistochemistry suggestive of metastatic adenocarcinoma. HR HPV E6/E7 RNA in situ hybridization (ISH) was positive. Bladder washing showed cytopathologic findings consistent with bladder involvement by small cell carcinoma. The patient's lesions in both urine and pleural fluids showed distinct cytomorphology. Within a year of diagnosis, the patient was declared deceased. This case highlights the existence of carcinoma admixed with NEC tumor, such as an HPV associated adenocarcinoma admixed with a NEC and underscores the elevated risk of HPV-related genital lesions in renal transplant patients. In patients with a history of solid organ transplant or other immunosuppressive conditions, there is an increased necessity for enhanced surveillance and appropriate cancer screening., (© 2024 Wiley Periodicals LLC.)

Overexpression of HPV-oncoproteins E6 and E7 is necessary for HPV-driven cervical carcinogenesis. Hence, these oncoproteins are promising disease-specific biomarkers. We assessed the technical and operational characteristics of the 8-HPV-type OncoE6/E7 Cervical Test in different laboratories using cervical samples from HPV-positive women living with (WLWH) and without HIV. The 8-HPV-type OncoE6/E7 Test (for short: "OncoE6/E7 test") was performed in 2833 HIV-negative women and 241 WLWH attending multicentric studies in Latin America (ESTAMPA study), and in Africa (CESTA study). Oncoprotein positivity were evaluated at each testing site, according to HIV status as well as type-specific agreement with HPV-DNA results. A feedback questionnaire was given to the operators performing the oncoprotein test to evaluate their impression and acceptability regarding the test. The OncoE6/E7 test revealed a high positivity rate heterogeneity across all testing sites (I 2 : 95.8%, p < .01) with significant lower positivity in WLWH compared to HIV-negative women (12% vs 25%, p < .01). A similar HPV-type distribution was found between HPV DNA genotyping and oncoprotein testing except for HPV31 and 33 (moderate agreement, k = 0.57). Twenty-one laboratory technicians were trained on oncoprotein testing. Despite operators' concerns about the time-consuming procedure and perceived need for moderate laboratory experience, they reported the OncoE6/E7 test as easy to perform and user-friendly for deployment in resource-limited settings. The high positivity rate variability found across studies and subjectivity in test outcome interpretation could potentially results in oncoprotein false positive/negative, and thus the need for further refinements before implementation of the oncoprotein testing in screen-triage-and-treat approaches is warranted., (© 2024 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Japan is lagging in cervical cancer prevention. The effectiveness of a self-sampling human papillomavirus (HPV) test, a possible measure to overcome this situation, has not yet been evaluated. A randomized controlled trial was performed to evaluate the effectiveness of a self-sampling HPV test on detection of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and screening uptake. Women between 30 and 58 years old who did not participate in the cervical cancer screening program for ≥3 years were eligible and assigned to the intervention group (cytology or self-sampling HPV test) or control group (cytology). Participants assigned to the intervention group were sent a self-sampling kit according to their ordering (opt-in strategy). A total of 7337 and 7772 women were assigned to the intervention and control groups, respectively. Screening uptake in the intervention group was significantly higher than that in the control group (20.0% vs. 6.4%; risk ratio: 3.10; 95% confidence interval [CI]: 2.82, 3.42). The compliance rate with cytology triage for HPV-positive women was 46.8% (95% CI: 35.5%, 58.4%). CIN2+ was detected in five and four participants in the intervention and control groups, respectively; there was no difference for intention-to-screen analysis (risk ratio: 1.32; 95% CI: 0.36, 4.93). Self-sampling of HPV test increased screening uptake; however, no difference was observed in the detection of CIN2+, probably due to the low compliance rate for cytology triage in HPV-positive women. Efforts to increase cytology triage are essential to maximize precancer detections., (© 2024 UICC.)

This study aimed to report the clinical outcomes and risk factors for survival of patients with low-risk early-stage human papillomavirus-associated (HPVA) endocervical adenocarcinoma (EAC) treated with surgery alone. This retrospective study obtained the clinicopathological data of patients with early-stage HPVA EAC who underwent surgery between 2012 and 2018. The Silva pattern of invasion was determined by reviewing pathology slides. Locoregional recurrence-free survival (RFS), RFS, and overall survival were calculated, and the risk factors for survival were analyzed. One hundred seventeen patients with a median follow-up of 5.2 years (0.5-9.7 yr) were included. The most common histologic type was usual (94/117, 80.3%). The Silva pattern was A in 79 patients (67.5%), B in 30 (25.6%), and C in 8 (6.8%). The 5-year locoregional RFS, RFS, and overall survival rates were 92.4%, 87.8%, and 97.2%, respectively. The presence of intermediate-risk factors and Silva pattern C were significantly associated with worse survival. Based on these findings, patients were categorized into 2 groups: Group 1 (Silva pattern A or Silva pattern B without intermediate-risk factors) and Group 2 (Silva pattern B with intermediate-risk factors or Silva pattern C ). Group 2 showed significantly worse outcomes than Group 1, including the 5-year locoregional RFS (98.6% vs 68.0%), RFS (96.4% vs 54.6%), and overall survival (100.0% vs 86.5%). In conclusion, surgery alone for early-stage HPVA EAC resulted in favorable outcomes. Consideration of the Silva pattern, in addition to well-known risk factors, could help in precise risk group stratification of low-risk, early-stage HPVA EAC., Competing Interests: H.S.K.’s work is supported by the National Research Foundation of Korea (NRF) grant funded by the Korean Government (MSIT; 2023R1A2C2006223). The remaining authors declare no conflict of interest., (Copyright © 2024 by the International Society of Gynecological Pathologists.)

Objectives: The aim of the study was to evaluate the clinical performance of HBRT-H14, a real-time PCR-based assay that separates human papillomavirus (HPV) 16 and HPV18 from 12 other high-risk (HR) HPV types, in population according to Chinese guideline., Methods: A total of 9829 eligible women aged 21-64 years from Henan, Shanxi, and Guangdong provinces were performed by HBRT-H14 testing and liquid-based cytology (LBC) screening at baseline and followed up for 3-year. The sensitivity, specificity, positive predictive value (absolute risk), and negative predictive value of LBC diagnosis and HPV testing were calculated for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) Lesions., Results: At baseline, 80 (0.81%) participants were diagnosed with CIN2+. HR-HPV with reflex LBC had a significantly higher sensitivity (78/80, 97.50% [95% CI, 91.34-99.31%] vs. 62/80, 77.50% [67.21-85.27%], McNemar's test p < 0.001), and a slightly lower specificity (8528/9749, 87.48% [86.80-88.12%] vs. 8900/9749, 91.29% [90.72-91.83%], McNemar's test p < 0.001) than LBC with reflex HR-HPV for CIN2+. 7832 (79.6%) participants completed 3-year follow-up and 172 (2.20%) participants were cumulatively diagnosed with CIN2+. Compared with LBC with reflex HR-HPV, HR-HPV with reflex LBC significantly increased the sensitivity (161/172, 93.60% [88.91-96.39%] vs. 87/172, 50.58% [43.18-57.96%], McNemar's test p < 0.001), but marginally decreased the specificity (6776/7660, 88.46% [87.72-89.16%] vs. 6933/7660, 90.51% [89.83-91.15], McNemar's test p < 0.001). In addition, the absolute 3-year risk of CIN2+ in HPV16/18-positive individuals was as high as 33% (80/238), whereas the risk in the HPV-negative population was only 0.16% (11/6787), much lower than those in the negative for intraepithelial lesion or malignancy population (1.21%, 85/7018). Moreover, similar results were found in women ≥30 years old., Discussion: The study has indicated that HBRT-14 has a reliable clinical performance for use in cervical screening. The validated HPV test would improve the quality of population screening., (Copyright © 2024. Published by Elsevier Ltd.)

High-risk human papillomavirus (HPV) infections can progress to cervical cancer which is the fourth most common cancer in women globally. In Scotland, the incidence of cervical cancer has a strong socioeconomic deprivation gradient disproportionately affecting women from more deprived areas. An HPV vaccination programme was initiated in Scotland in 2008 targeting girls aged 12-13 years with a catch-up campaign running for the first three years for girls aged up to 18 years. The programme has evolved over the last 16 years with changes in the type of vaccine, dosing schedules and the extension of the programme to boys and gay, bisexual and other men who have sex with men. Vaccine uptake in Scotland has historically been high but has gradually decreased over time and disparities exist in women from more deprived areas of Scotland. The ability to link national immunisation and screening databases in Scotland has allowed direct monitoring of the impact of the HPV vaccine on virological and histological outcomes. Analyses of this linked data have demonstrated real-world evidence of high vaccine effectiveness against HPV infection, cervical disease, and cervical cancer with evidence of herd immunity in unvaccinated women. Continued monitoring is crucial to assess the duration of protection, the impact of vaccine and dosing schedules changes and the emergence of potential type replacement. With the World Health Organisation's aim to eliminate cervical cancer as a public health problem by the next century addressing the inequalities in cervical cancer incidence will be crucial. This will require targeted interventions for women most at risk of cervical cancer to ensure elimination is achieved timely for all women in Scotland., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kate Cuschieri reports a relationship with Hologic Inc. that includes: funding grants and travel reimbursement. Kate Cuschieri reports a relationship with Barinthus Biotherapeutics plc that includes: funding grants and non-financial support. Kate Cuschieri reports a relationship with EUROIMMUN Medizinische Labordiagnostika AG that includes: funding grants. Kate Cuschieri reports a relationship with GeneFirst that includes: funding grants. Kate Cuschieri reports a relationship with Hiantis that includes: funding grants. Kate Cuschieri reports a relationship with Seegene, Inc. that includes: funding grants. Kate Cuschieri reports a relationship with Roche that includes: funding grants. Kate Cuschieri reports a relationship with Daye that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The E6 protein is a known oncogene in cervical cancer and plays a key role in the development and progression of cervical cancer by reducing the expression level of the tumor suppressor protein P53 and ultimately leading to enhanced cell proliferation and reduced apoptosis. Therefore, antiviral agents that inhibit the expression of E6 oncoprotein are expected to be potential therapies for human cervical cancer. Here we developed CRISPR/Cas13a: crRNA dual plasmid system and demonstrated that CRISPR/Cas13a could effectively and specifically knock down human papillomavirus 18 E6 mRNA, downregulate the expression level of E6 protein, and restore the expression of the tumor suppressor gene P53 protein, thereby inhibiting the growth of cervical cancer cells and increasing their apoptosis, the E6-2, E6-3, and E6-5 groups resulted in apoptosis rates of 25.4%, 22.4%, and 22.2% in HeLa cells. Moreover, CRISPR/Cas13a enhances the proliferation inhibition and apoptosis induction of cisplatin in cervical cancer HeLa cells. The CRISPR/Cas13a system targeting HPV E6 mRNA may be a promising therapeutic approach for the treatment of human papillomavirus-associated cervical cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: In this study, we aimed to validate the performance of the PAX1 and JAM3 methylation (PAX1 m /JAM3 m ) test as a triage tool for detecting cervical intraepithelial neoplasia grade 3 or worse (CIN3 +) in non-16/18 high-risk human papillomavirus-positive patients (non-16/18 hrHPV +)., Methods: The triage performance of liquid-based cytology (LBC) and the PAX1 m /JAM3 m test for detecting CIN3 + were compared., Results: In total, 1851 participants had cervical histological outcomes and were included in the analysis. The sensitivity/specificity of the LBC test results with atypical squamous cells of undetermined significance or worse (LBC ≥ ASCUS) and the PAX1 m /JAM3 m test were 90.1%/26.7% and 84.8%/88.5%, respectively. PAX1 m /JAM3 m ( +) had the highest diagnostic AUC (0.866, 95% confidence interval (CI) 0.837-0.896) in the whole cohort. All cancers (n = 20) were detected by PAX1 m /JAM3 m (+). Compared with LBC ≥ ASCUS, PAX1 m /JAM3 m (+) reduced the number of patients who needed referral for colposcopy by 57.21% (74.66% vs. 17.45%). The odds ratios for detecting CIN3 + by LBC ≥ ASCUS and PAX1 m /JAM3 m (+) were 3.3 (95% CI 2.0-5.9) and 42.6 (27.1-69.6), respectively (p < 0.001). The combination of LBC ≥ ASCUS or PAX1 m /JAM3 m (+) slightly increased the diagnostic sensitivity (98.0%, 95% CI: 95.8-100%) and referral rate (77.09%) but reduced the diagnostic specificity (24.8%, 22.7-26.8%)., Conclusions: In non-16/18 hrHPV(+) women, PAX1 m /JAM3 m was superior to cytology for detecting CIN3 + . Compared with LBC ≥ ASCUS, PAX1 m /JAM3 m (+) reduced the number of significant referrals to colposcopy without compromising diagnostic sensitivity., (© 2024. The Author(s).)

Despite recent medical progress, cervical cancer remains a major global health concern for women. Current standard treatments have limitations such as non-specific toxicity that necessitate development of safer and more effective therapeutic strategies. This research evaluated the combinatorial effects of olive leaf extract (OLE), rich in anti-cancer polyphenols, and the oncolytic Newcastle disease virus (NDV) against human cervical cancer cells. OLE was efficiently encapsulated (>94% loading) within MF59 lipid nanoparticles and nanostructured lipid carriers (NLCs; contains Precirol as NLC-P, contains Lecithin as NLC-L) to enhance stability, bioavailability, and targeted delivery. Physicochemical analysis confirmed successful encapsulation of OLE within nanoparticles smaller than 150 nm. In vitro cytotoxicity assays demonstrated significantly higher toxicity of the OLE-loaded nanoparticle formulations on HeLa cancer cells versus HDF normal cells (P<0.05). MF59 achieved the highest encapsulation efficiency, while NLC-P had the best drug release profile. NDV selectively infected and killed HeLa cells versus HDF cells. Notably, combining NDV with OLE-loaded nanoparticles led to significantly enhanced synergistic cytotoxicity against cancer cells (P<0.05), with NLC-P (OLE) and NDV producing the strongest effects. Apoptosis and cell cycle analyses confirmed the increased anti-cancer activity of the combinatorial treatment, which induced cell cycle arrest. This study provides evidence that co-delivery of OLE-loaded lipid nanoparticles and NDV potentiates anti-cancer activity against cervical cancer cells in vitro through a synergistic mechanism, warranting further development as a promising alternative cervical cancer therapy., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Golalipour et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

A substantial percentage of the population remains at risk for cervical cancer due to pre-existing human papillomavirus (HPV) infections, despite prophylactic vaccines. Early diagnosis and treatment are crucial for better disease outcomes. The development of new treatments heavily relies on suitable preclinical model systems. Recently, we established a mouse papillomavirus (MmuPV1) model that is relevant to HPV genital pathogenesis. In the current study, we validated the use of Papanicolaou (Pap) smears, a valuable early diagnostic tool for detecting HPV cervical cancer, to monitor disease progression in the MmuPV1 mouse model. Biweekly cervicovaginal swabs were collected from the MmuPV1-infected mice for viral DNA quantitation and cytology assessment. The Pap smear slides were evaluated for signs of epithelial cell abnormalities using the 2014 Bethesda system criteria. Tissues from the infected mice were harvested at various times post-viral infection for additional histological and virological assays. Over time, increased viral replication was consistent with higher levels of viral DNA, and it coincided with an uptick in epithelial cell abnormalities with higher severity scores noted as early as 10 weeks after viral infection. The cytological results also correlated with the histological evaluation of tissues harvested simultaneously. Both immunocompromised and immunocompetent mice with squamous cell carcinoma (SCC) cytology also developed vaginal SCCs. Notably, samples from the MmuPV1-infected mice exhibited similar cellular abnormalities compared to the corresponding human samples at similar disease stages. Hence, Pap smear screening proves to be an effective tool for the longitudinal monitoring of disease progression in the MmuPV1 mouse model., Importance: Papanicolaou (Pap) smear has saved millions of women's lives as a valuable early screening tool for detecting human papillomavirus (HPV) cervical precancers and cancer. However, more than 200,000 women in the United States alone remain at risk for cervical cancer due to pre-existing HPV infection-induced precancers, as there are currently no effective treatments for HPV-associated precancers and cancers other than invasive procedures including a loop electrosurgical excision procedure (LEEP) to remove abnormal tissues. In the current study, we validated the use of Pap smears to monitor disease progression in our recently established mouse papillomavirus model. To the best of our knowledge, this is the first study that provides compelling evidence of applying Pap smears from cervicovaginal swabs to monitor disease progression in mice. This HPV-relevant cytology assay will enable us to develop and test novel antiviral and anti-tumor therapies using this model to eliminate HPV-associated diseases and cancers., Competing Interests: The authors declare no conflict of interest.

Introduction: Primary Human Papilloma Virus (HPV) testing offers higher sensitivity and specificity over Visual Inspection using Acetic acid (VIA) in cervical cancer screening. Self-sampling is a promising strategy to boost participation and reduce disparities. However, concerns about the initial costs hinder HPV testing adoption in low and middle-income countries. This study assesses the cost-utility of home-based HPV self-sampling versus VIA for cervical cancer screening in India., Methods: A cross-sectional study was conducted in East district, Sikkim, India, comparing the costs and utility outcomes of population-based cervical cancer screening through VIA and primary HPV screening through self-sampling. Cost-related data were collected from April 2021 to March 2022 using the bottom-up micro-costing method, while utility measures were collected prospectively using the EuroQoL-5D-5L questionnaire. The utility values were converted into quality-adjusted life days (QALDs) for an 8-day period. The willingness to pay threshold (WTP) was based on per capita GDP for 2022. If the calculated Incremental Cost-Effectiveness Ratio (ICER) value is lower than the WTP threshold, it signifies that the intervention is cost-effective., Results: The study included 95 women in each group of cervical cancer screening with VIA & HPV self-sampling. For eight days, the QALD was found to be 7.977 for the VIA group and 8.0 for the HPV group. The unit cost per woman screened by VIA and HPV self-testing was ₹1,597 (US$ 19.2) and ₹1,271(US$ 15.3), respectively. The ICER was ₹-14,459 (US$ -173.6), which was much below the WTP threshold for eight QALDs, i.e. ₹ 4,193 (US$ 50.4)., Conclusion: The findings support HPV self-sampling as a cost-effective alternative to VIA. This informs policymakers and healthcare providers for better resource allocation in cervical cancer screening in Sikkim., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Hariprasad et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: It is important to assess the relationship between specific HPV genotype or multiple infection and cervical cytology. The protection provided by the HPV vaccine is type-specific, and the epidemiology feature of coinfections needs to be investigated. The aim is to provide baseline information for developing HPV vaccination and management of HPV-positive populations in the region., Methods: A total of 3649 HPV-positive women were collected from 25,572 women who underwent 15 HR-HPV genotypes and ThinPrep cytologic test (TCT) results. Logistic regression was used to determine the correlation between the risk of cytology abnormalities and specific HPV infection. We calculated odds ratios (ORs) to assess coinfection patterns for the common two-type HPV infections. chi-squared test was used to estimate the relationship between single or multiple HPV (divided into species groups) infection and cytology results., Results: The results showed there was a positive correlation between HPV16 (OR = 4.742; 95% CI 3.063-7.342) and HPV33 (OR = 4.361; 95% CI 2.307-8.243) infection and HSIL positive. There was a positive correlation between HPV66 (OR = 2.445; 95% CI 1.579-3.787), HPV51 (OR = 1.651; 95% CI 1.086-2.510) and HPV58(OR = 1.661; 95% CI 1.166-2.366) infection and LSIL. Multiple HPV infections with α9 species (OR = 1.995; 95% CI 1.101-3.616) were associated with a higher risk of high-grade intraepithelial lesions (HSIL) compared with single HPV infection. There were positive correlations between HPV66 and HPV56 (α6) (OR = 3.321; 95% CI 2.329-4.735) and HPV39 and HPV68 (α7). (OR = 1.677; 95% CI 1.127-2.495). There were negative correlations between HPV52, 58, 16 and the other HPV gene subtypes., Conclusion: HPV33 may be equally managed with HPV16. The management of multiple infections with α9 may be strengthened. The 9-valent vaccine may provide better protection for the population in Chongqing currently. The development of future vaccines against HPV51 and HPV66 may be considered in this region., (© 2024. The Author(s).)

Background: Persistent infection with high-risk human papillomavirus (HR-HPV) plays a key role in the onset of cervical cancer. This study was designed to examine the epidemiological trends and genotype distribution of HPV from 2014 to 2023 in the plateau region of Southwest China., Methods: The findings could offer valuable insights for clinical screening of cervical cancer and the formulation of HPV vaccination policies. This retrospective study analyzed 66,000 women who received HPV-DNA testing at the First People's Hospital of Qujing, Yunnan, China, between 2014 and 2023. The cohort consisted of 33,512 outpatients, 3,816 inpatients, and 28,672 individuals undergoing health examinations. Cervical cells were collected for DNA extraction, and PCR amplification along with Luminex xMAP technology were used to detect 27 HPV genotypes. The data analysis was conducted using GraphPad Prism and IBM SPSS Statistics 27 software., Results: The overall HPV infection rate at the First People's Hospital of Qujing declined from 24.92% in 2014 to 16.29% in 2023, averaging 16.02%. Specific infection rates were 18.50% among outpatients, 12.97% among inpatients, and 13.53% for health examination attendees. The predominant high-risk HPV genotypes identified were HPV52 (2.61%), HPV16 (2.06%), HPV58 (1.81%), HPV53 (1.55%), and HPV39 (1.09%). Meanwhile, the most frequent low-risk HPV genotypes were HPV6 (1.30%), HPV61 (1.21%), and HPV11 (0.85%). In HPV-positive cases, the distribution of single, double, triple, and quadruple or more infections were 79.90%, 15.17%, 3.59%, and 1.33%, respectively. The proportions of pure LR-HPV, pure HR-HPV, and mixed infections were 22.16%, 67.82%, and 10.02%, respectively. Age-specific analysis revealed a bimodal distribution of HPV infection, with the infection rate rapidly decreasing from 44.02% in the ≤ 19 age group to 19.55% in the 20-29 age group and 13.84% in the 30-39 age group, followed by a gradual increase to 14.64% in the 40-49 age group, 16.65% in the 50-59 age group, and 22.98% in the ≥ 60 age group. The coverage rates of the three available vaccines are all below 50%. The results of this study indicated a declining trend in HPV prevalence in the plateau region of Southwest China over the period from 2014 to 2023, especially in the reduction of genotypes targeted by vaccines., Conclusion: There were significant variations in the genotypes prevalent among different age groups, years, and patient sources within the same region. The underwhelming vaccination rates emphasize the critical need for developing either a multivalent vaccine or a personalized vaccine that targets the HPV genotypes common in the Chinese population. Furthermore, vaccinating adolescents to curb HPV infection and ensuring regular cervical cancer screenings for postmenopausal women are crucial steps., (© 2024. The Author(s).)

HPV 18 caused 19  percent of all cervical cancer cases in Sweden, in particular adenocarcinomas. High vaccination coverages are required to eliminate the most oncogenic HPV types like HPV 16 and HPV 18, while medium-oncogenic viruses such as HPV 31, 33, 45, 52, and 58 are easier to eliminate due to their lower reproduction number. Women born 1994-1998 were offered catch-up vaccination against HPV 16 and HPV 18 at ages 13-18, but only about 55 percent participated, which is insufficient to eliminate these viruses. Offering vaccination against HPV 16, 18, 31, 33, 45, 52, and 58 to women born in 1994-1998 and achieving around 70 percent participation should eliminate the medium-oncogenic viruses and achieve population immunity also for HPV 16/18. A national project offering free vaccines and screening against these HPV types is ongoing since 2021. Already at the start of the project, there was only a single case of HPV 18 in age groups with high vaccination coverage, implying that extinction of this virus is imminent.

Clinically validated human papillomavirus (HPV) assays are crucial in cervical cancer screening. In this study, we evaluated the Allplex HPV HR Detection assay (Seegene, SouthKorea) for its clinical accuracy and reproducibility according to the international criteria, using the RealTime High Risk HPV m2000 assay (Abbott, USA) as standard comparator. The Allplex HPV HR assay exhibits significant non-inferior sensitivity to detect cervical intraepithelial neoplasia grade (CIN) 2 or worse (CIN2+) with a ratio of 1.00 (95% CI: 0.97-1.03, P = 0.006), insignificant non-inferior sensitivity to detect CIN3+ with a ratio of 1.00 (95% CI: 0.88-1.13, P = 0.098), and non-inferior specificity to exclude CIN2+ with a ratio of 0.99 (95% CI: 0.99-1.00, P < 0.001) compared to the standard comparator. In addition, the assay shows an excellent reproducibility within the same laboratory [96.5% (95% CI: 94.6-97.9) with a kappa value of 0.91 (95% CI: 0.87-0.95)] and between laboratories [96.7% (95% CI: 94.8-98.0) with a kappa value of 0.91 (95% CI: 0.87-0.95)] for overall high-risk HPV positivity as well as for each individual HPV type. Pooling our study data with those of another independent study supports the consistency of our findings. We conclude that both the clinical accuracy to detect cervical precancer and the reproducibility of Allplex HPV HR Detection assay fulfill the international validation criteria of use in cervical cancer screening.IMPORTANCEThe clinical validation of human papillomavirus (HPV) assays in accordance with well-established international guidelines is crucial to ensure that only validated assays are used in the context of screening (Meijer et al., Int J Cancer, 2009). The guidelines, developed by an international consortium, require that a novel HPV assay has non-inferior accuracy against a standard comparator test for the detection of cervical intraepithelial neoplasia grade (CIN) 2 or worse (CIN2+). Additionally, a new HPV assay should meet specific criteria for both intra- and inter-laboratory reproducibility to ensure the assay consistently exhibits technical precision and robust performance. Pooling our study data with those of another independent study supports the consistency of our findings. In conclusion, both the clinical accuracy to detect cervical precancer and the reproducibility of Allplex HPV HR Detection assay fulfill the international validation criteria of use in cervical cancer screening., Competing Interests: The authors declare no conflict of interest.

Objective: Cervical cancer, linked to human papillomavirus (HPV), ranks fourth among women's cancers globally. Several studies have found an association between viral infections or cancer and dementia, which is a major public health concern. This study aimed to provide real-world data on the association between cervical cancer and the risk of dementia., Methods: This population-based cohort study, utilizing Taiwan's National Health Insurance Research Database, included 53 905 patients, with 10 781 having cervical cancer, matching with 43 124 controls in a 1:4 ratio based on age and indexed date. Incidence density rates were used to calculate the incidence rate of dementia. Adjusting for comorbidities, a multivariable Cox proportional hazards regression model was used to estimate the hazard ratios and 95% confidence intervals. Additionally, the risk of dementia was further verified using the cumulative incidence analyzed by the Kaplan-Meier method., Results: This study indicated a significantly higher dementia risk in the cervical cancer cohort compared with the non-cervical cancer cohort (adjusted HR (aHR)=1.64, 95% CI 1.16 to 2.26; p<0.001), suggesting a 1.64-fold increased risk. Notably, cervical cancer posed a greater risk of dementia (aHR=1.69, 95% CI 1.21 to 2.29; p<0.001) compared with carcinoma in situ of the cervix (p=0.18) and cervical intraepithelial neoplasia (p=0.23). The cumulative incidence of dementia in the cervical cancer group was significantly higher (log-rank test, p<0.001) than the control group., Conclusions: Cervical cancer (invasive disease) was associated with a significant risk of dementia, unlike carcinoma in situ of the cervix and cervical intraepithelial neoplasia (pre-invasive diseases), suggesting HPV infections may play a role in dementia, particularly oncogenic types. This highlights the importance of further investigation into the underlying mechanisms of the association between cervical cancer and dementia., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Understanding the proportion of invasive cervical cancer (ICC) caused by different human papillomavirus (HPV) genotypes can inform primary (ie, vaccination) and secondary (ie, screening) prevention efforts that target specific HPV genotypes. However, using the global literature to estimate population attributable fractions (AFs) requires a methodological framework to address HPV genotype-specific causality from aggregated data. We aimed to estimate the proportion of ICC caused by different HPV genotypes at the global, regional, and national level., Methods: This systematic review identified studies reporting HPV genotype-specific prevalence in ICC or people with normal cervical cytology. We searched PubMed, Embase, Scopus, and Web of Science up to Feb 29, 2024, using the search terms "cervix" and "HPV", with no language restrictions. Odds ratios (ORs) were estimated by comparing HPV genotype-specific prevalence between HPV-positive ICC and normal cervical cytology with logistic regression models, adjusting for region, year of paper publication, and HPV primer or test. HPV genotypes with a lower bound to the 95% CI of the OR greater than 1·0 were judged as causal to ICC. Corresponding regional genotype-specific AFs were calculated as regional HPV prevalence in ICC multiplied by (1 - [1 / OR]) and were proportionally adjusted to total 100%. Global AFs were calculated from regional AFs weighted by number of regional ICC cases in 2022 (GLOBOCAN)., Findings: The systematic review identified 1174 studies with 111 902 cases of HPV-positive ICC and 2 755 734 of normal cervical cytology. 17 HPV genotypes were considered causal to ICC, with ORs ranging widely from 48·3 (95% CI 45·7-50·9) for HPV16 to 1·4 (1·2-1·7) for HPV51. HPV16 had the highest global AF (61·7%), followed by HPV18 (15·3%), HPV45 (4·8%), HPV33 (3·8%), HPV58 (3·5%), HPV31 (2·8%), and HPV52 (2·8%). Remaining causal genotypes (HPV35, 59, 39, 56, 51, 68, 73, 26, 69, and 82) had a combined global AF of 5·3%. AFs for HPV16 and 18 and HPV16, 18, 31, 33, 45, 52, and 58 combined were lowest in Africa (71·9% and 92·1%, respectively) and highest in central, western, and southern Asia (83·2% and 95·9%, respectively). HPV35 had a higher AF in Africa (3·6%) than other regions (0·6-1·6%)., Interpretation: This study provides a comprehensive global picture of HPV genotype-specific AFs in ICC, before the influence of HPV vaccination. These data can inform HPV genotype-specific vaccination and screening strategies to reduce the burden of ICC., Funding: EU Horizon 2020 Research and Innovation Programme., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 World Health Organization. Published by Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Nitric oxide (NO) may contribute to the persistence of high-risk human papillomavirus (hrHPV) infection, which has been linked to the development of premalignant lesions and cervical cancer. Our study aimed to examine the relationship between cervical NO metabolite (NOx) levels, hrHPV infection, and cytopathological findings. Additionally, we assessed cervical NOx levels as a biomarker for predicting hrHPV infection and epithelial atypia., Methods: The study involved 74 women who attended the Gynecology and Obstetrics outpatient clinics at Cairo University Hospitals between November 2021 and August 2022. Cervical samples were subjected to Pap testing, assessment of NOx levels by the Griess method, and detection of hrHPV DNA by real-time polymerase chain reaction., Results: High-risk HPV was detected in 37.8% of women. EA was found in 17.1% of cases, with a higher percentage among hrHPV-positive than negative cases (35.7% vs. 4.3%, p = 0.001). The most prevalent hrHPV genotype was HPV 16 (89.3%). The cervical NOx level in hrHPV-positive cases was significantly higher (37.4 µmol/mL, IQR: 34.5-45.8) compared to negative cases (2.3 µmol/mL, IQR: 1.2-9.8) (p = < 0.001). Patients with high-grade atypia showed significantly higher NOx levels (38.0 µmol/mL, IQR: 24.6-94.7) in comparison to NILM and low-grade atypia cases (5.0 µmol/mL, IQR: 1.6-33.3 and 34.5 µmol/mL, IQR: 11.7-61.7, respectively) (p = 0.006). Although the NOx levels among hrHPV-positive cases with low-grade atypia (40.4 µmol/mL, IQR: 33.3‒61.8) were higher than those with NILM (36.2 µmol/mL, IQR: 35.7‒44.0) and high-grade atypia (38.0 µmol/mL, IQR: 24.6‒94.7), the difference was not significant (p = 0.771). ROC curve analysis indicated that the cervical NOx cut-off values of > 23.61 µmol/mL and > 11.35 µmol/mL exhibited good diagnostic accuracy for the prediction of hrHPV infection and EA, respectively., Conclusions: The high prevalence of hrHPV infection, particularly HPV 16, in our hospital warrants targeted treatment and comprehensive screening. Elevated cervical NOx levels are associated with hrHPV infection and high-grade atypia, suggesting their potential use as biomarkers for predicting the presence of hrHPV and abnormal cytological changes., (© 2024. The Author(s).)

Background: Cervical cancer, predominantly caused by the human papillomavirus (HPV), is a major health challenge in India, with high morbidity and mortality rates. Given India's vast geographic and socio-economic diversity, understanding regional variations in HPV prevalence is crucial for developing targeted and effective public health interventions. This systematic review and meta-analysis were conducted to elucidate the prevalence of HPV among cervical cancer patients in India., Methods: A literature search was executed across PubMed, EMBASE, and Web of Science up to December 07, 2023. Observational studies reporting HPV prevalence among cervical cancer patients in India are included. A Modified Newcastle-Ottawa scale was used for quality assessment. A random-effects meta-analysis was used to determine pooled HPV prevalence, and heterogeneity was evaluated using the I² statistic. Subgroup and sensitivity analyses were performed to assess result stability and investigate heterogeneity sources. All statistical analyses were performed using R software version 4.3., Results: The meta-analysis included 17 studies with a total of 2529 cervical cancer cases, of which 1977 were HPV-positive. The pooled HPV prevalence was 85% (95% CI: 71-92%), with substantial heterogeneity (I² = 94%). Subgroup analysis by geographic zones showed notable differences: South (88%, 95% CI: 76-95%), North (73%, 95% CI: 1-100%), East (99%, 95% CI: 1-100%), Central (71%, 95% CI: 54-84%), and West (77%, 95% CI: 0-100%). Sensitivity analysis demonstrated the consistency of the results, and a reanalysis, excluding influential studies, yielded a prevalence of 82% (95% CI: 67-91%)., Conclusion: Our analysis reveals a high prevalence of HPV in cervical cancer patients in India, with significant regional variations. The observed heterogeneity highlights the complexity of HPV epidemiology in India and necessitates further research to explore underlying causes and regional characteristics. Future studies should aim to expand geographic representation and deepen understanding of the factors contributing to the variability in HPV prevalence., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: This pilot study is aimed to analyze a novel strategy of cervical cancer screening by training of Accredited Social Health Activist (ASHA) workers via telemedicine to counsel women for human papillomavirus (HPV) self-sampling., Materials and Methods: This is a pilot, community-based, prospective, single-arm study. Physicians trained the ASHA workers regarding self-sampled HPV testing via a mobile application and telephonically using videos and e-pamphlets, who in turn trained the clients in community. The HPV kits were transported via prepaid courier service., Results: Four hundred and sixty-five women of age group 30-65 years were tested by 47 teletrained ASHA workers. The mean age of ASHA worker and clients was 39.47 ± 6.45 and 37.26 ± 8.38 years, respectively. Of the ASHA workers, 91.7% were satisfied with the information provided during telecounseling, 95.7% could understand the contents of mobile app easily, and 93.6% could fill the data of clients in app easily. Of the clients, 99.6% were satisfied with counseling by ASHA workers and 98% found it easy to self-sample. The acceptability of this strategy among clients was 58.2%. The feasibility of this strategy (percentage of clients who find it easy/those who did self-sampling) was around 99%. Among those screened, 11.8% were high-risk HPV-positive and 85.5% had follow-up at the study center., Conclusion: The current study highlights a novel strategy of cervical cancer screening by incorporating the role of telemedicine in training ASHA workers and their role in improving the screening by home-based delivery of HPV kits with promising results.

Background: Latinas experience the greatest cervical cancer incidence compared with other ethnic/racial groups in the United States (US) due in part to significant disparities in screening uptake. Social and structural conditions that impede access to and participation in screening include language barriers, concerns about documentation status, logistical issues (e.g., transportation, limited clinic hours), and cultural beliefs regarding modesty and promiscuity. To overcome these challenges, self-sampling for human papillomavirus (HPV) DNA testing has emerged as a potentially promising method for promoting cervical cancer screening among this population. Thus, this systematic review aimed to assess the acceptability of HPV self-sampling among US Latinas., Methods: Using EBSCOhost and PubMed databases, we searched for studies published in the past two decades (2003-2023) that described participation in HPV self-sampling among Latinas. Eleven articles met inclusion criteria., Results: The majority of studies were conducted in Florida, California, and Puerto Rico, were single-arm designs, and involved the use of community health workers and Spanish-language materials (e.g., brochures). Across studies, the majority of participants reported that self-sampling was acceptable with respect to ease of use, comfort (lack of pain), privacy, and convenience; however, some women were concerned about the accuracy of self-sampling or whether they had performed sample collection correctly., Conclusion: Given the high acceptability, self-collection of cervicovaginal samples for HPV testing may offer a feasible option for enhancing participation in cervical cancer screening in this population that encounters significant barriers to screening., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Persistent human papillomavirus (HPV) infection remains a key risk factor for cervical cancer. HPV-based primary screening is widely recommended in clinical guidelines, and further longitudinal studies are needed to optimize strategies for detecting high-grade cervical lesions compared to cytology., Methods: From November 2015 to December 2023, 31,942 participants were included in the real-world observational study. Among those, 4,219 participants underwent at least two rounds of HPV tests, and 397 completed three rounds of HPV tests. All participants were tested for high-risk types of HPV 16/18/31/33/35/39/45/51/52/56/58/59/66/68 (hrHPV) and low-risk types of HPV6/11 genotyping. Some participants also received cytology or colposcopy with pathology., Results: In the cross-sectional cohort, the prevalence of hrHPV and all HPV subtypes was 6.6% (2,108/31,942) and 6.8% (2,177/31,942), respectively. The three top hrHPV genotypes were HPV52 (1.9%), HPV58 (0.9%), and HPV16 (0.9%). Age distributions showed two peaks at 45-49 and 60-65 years. For the primary screening cohort, the hrHPV prevalence rate increased from 4.8% in 2015-2017 to 7.0% in 2020-2020 and finally reached 7.2% in 2023. For the longitudinal cohort study, the hrHPV prevalence rates in the repeated population (3.9, 5.3, and 6.0%) were lower than the primary hrHPV screening rates (6.6%), which indicated that repeated screening might decrease the prevalence rate. Methodologically, the hrHPV (89.5%) and the screening group of 16 subtypes (92.3%) demonstrated superior sensitivity than the cytology group (54.4%). Moreover, the longitudinal study indicated that the persistent hrHPV subgroup had a significantly higher ( p  = 0.04) incidence of high-grade squamous intraepithelial lesions and more histology progression events (7/17 vs. 0/5) than the reinfection group., Conclusion: The study indicates a rising high-risk HPV prevalence in Dongguan, with repeated screening reducing this trend. The findings support HPV-based primary screening and might guide HPV vaccination and cervical cancer prevention in South China., Competing Interests: Author BC was employed by company BGI Genomics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhong, Pan, Chen, Gu, Liang, Sun, Huang, Yuan, Guo, Zhong, Li, Zhou, Zeng and Tang.)

Background: Human papillomavirus (HPV) infection is strongly associated with cervical cancer with almost all cases being associated with the infection. Cervical cancer is the leading cause of cancer death among women in Zambia and the fourth leading cause of cancer death in women worldwide. However, there is limited data on the burden and associated factors of HPV in sub-Saharan Africa. This study therefore aimed to determine the prevalence and correlates of HPV infection in the Southern province of Zambia., Methods: This was a cross-sectional study conducted at Livingstone University Teaching Hospital (LUTH) among 4,612 women from different districts of the southern province being screened for HPV infection between September 2021 and August 2022. Demographic and clinical data were collected from an existing laboratory programmatic database. Multivariable logistic regression was used to estimate the factors associated with HPV infection., Results: The study participants had a median age of 39 years [interquartile range (IQR) 30, 47]. The prevalence of HPV infection was 35.56% (95%CI). At multivariable analysis, the factors associated with a positive HPV result were younger age (adjusted odds ratio (AOR) 0.98; 95% confidence interval (CI) 0.98-0.99; p. value 0.001), having provider collected sample (AOR 2.15; 95%CI 1.66-2.79; p. value <0.001) and living with HIV (AOR 1.77; 95%CI 1.22-2.55; p. value <0.002)., Conclusion: The prevalence of HPV in women in the southern province of Zambia is high, and likely influenced by age and HIV status. Additionally, the outcome of the HPV test is affected by the sample collection method. Therefore, there is a necessity to enhance HPV and cervical cancer screening, especially among people with HIV., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Muchaili et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Cervical cancer screening has reduced morbidity and mortality in many countries, but efforts to optimize screening modalities and schedules are ongoing. Using data from a randomized trial conducted in British Columbia, Canada, in conjunction with a provincial screening registry, Gottschlich and colleagues demonstrated that the estimated risk for precancerous disease (cervical intraepithelial neoplasia grades 2 or worse) at 8 years following a negative human papillomavirus (HPV) test was similar to the current standard of care (Pap testing after 3 years). The study supports extending screening intervals for those with a negative HPV test beyond currently recommended 5-year intervals. In an ideal world, the resources saved through less frequent routine cervical screening could be redirected to increasing screening uptake and follow-up of abnormalities to improve equity in cervical cancer prevention. However, implementation of extending screening intervals remains less than straightforward in settings with fragmented healthcare systems that lack information systems to support patient call/recall, such as the United States. To achieve the full promise of primary HPV testing, stakeholders at every level must commit to identifying and addressing the diverse spectrum of barriers that undergird existing inequities in care access, appropriately resource implementation strategies, and improve health information systems. See related article by Gottschlich et al., p. 904., (©2024 The Authors; Published by the American Association for Cancer Research.)

The Netherlands' cervical cancer screening program transitioned to primary human papillomavirus (HPV) screening in 2017. After the introduction of HPV-based screening, the country saw increases in colposcopy referral rates and detections of low-grade lesions. In July 2022, genotyping was introduced, and those with borderline or mild dyskaryotic (BMD) cytologic abnormalities were only referred to colposcopy if positive for HPV type 16 or 18, and repeat screening otherwise. In this article, various strategies using extended genotyping (HPV16/18/31/33/45/52/58) as a triage test after an abnormal screen were explored using data from HPV-positive participants with normal or BMD cytology in the Population-Based Screening Study Amsterdam (POBASCAM) trial. The authors assessed positive and negative predictive values and colposcopy referral rates for each strategy using extended genotyping to triage women to either direct referral to colposcopy or repeat screening. Direct referral did not meet positive and negative predictive value thresholds for efficiency for any strategies. However, the authors note that direct referral may nonetheless be useful among those with BMD due to minimal increases in colposcopy referrals and concerns of loss to follow-up at repeat screening. These findings demonstrate the potential utility of extended genotyping as a triage test in primary HPV screening programs. The results should be considered alongside the fact that referral to repeat screening may result in loss of engagement of women who need treatment to prevent invasive cancer. See related article by Kroon et al., p. 1037., (©2024 American Association for Cancer Research.)

The risk associated with single and multiple human papillomavirus (HPV) infections in cervical intraepithelial neoplasia (CIN) remains uncertain. This study aims to explore the distribution and diagnostic significance of the number of high-risk HPV (hr-HPV) infections in detecting CIN, addressing a crucial gap in our understanding. This comprehensive multicenter, retrospective study meticulously analyzed the distribution of single and multiple hr-HPV, the risk of CIN2+, the relationship with CIN, and the impact on the diagnostic performance of colposcopy using demographic information, clinical histories, and tissue samples. The composition of a single infection was predominantly HPV16, 52, 58, 18, and 51, while HPV16 and 33 were identified as the primary causes of CIN2+. The primary instances of dual infection were mainly observed in combinations such as HPV16/18, HPV16/52, and HPV16/58, while HPV16/33 was identified as the primary cause of CIN2+. The incidence of hr-HPV infections shows a dose-response relationship with the risk of CIN (p for trend <0.001). Compared to single hr-HPV, multiple hr-HPV infections were associated with increased risks of CIN1 (1.44, 95% confidence interval [CI]: 1.20-1.72), CIN2 (1.70, 95% CI: 1.38-2.09), and CIN3 (1.08, 95% CI: 0.86-1.37). The colposcopy-based specificity of single hr-HPV (93.4, 95% CI: 92.4-94.4) and multiple hr-HPV (92.9, 95% CI: 90.8-94.6) was significantly lower than negative (97.9, 95% CI: 97.0-98.5) in detecting high-grade squamous intraepithelial lesion or worse (HSIL+). However, the sensitivity of single hr-HPV (73.5, 95% CI: 70.8-76.0) and multiple hr-HPV (71.8, 95% CI: 67.0-76.2) was higher than negative (62.0, 95% CI: 51.0-71.9) in detecting HSIL+. We found that multiple hr-HPV infections increase the risk of developing CIN lesions compared to a single infection. Colposcopy for HSIL+ detection showed high sensitivity and low specificity for hr-HPV infection. Apart from HPV16, this study also found that HPV33 is a major pathogenic genotype., (© 2024 Wiley Periodicals LLC.)

Objective: High-risk human papillomavirus (HR-HPV) infection is the chief cause of cervical intraepithelial neoplasia (CIN) and cervical carcinoma. The Erhuang suppository (EHS) is a traditional Chinese medicine (TCM) prepared from realgar (As 2 S 2 ), Coptidis rhizoma, alumen, and borneolum syntheticum and has been used for antiviral and antitumor purposes. However, whether EHS can efficiently alleviate HR-HPV infection remains unclear. This study was conducted to evaluate the efficacy of EHS for the treatment of persistent HR-HPV infection in the uterine cervix., Methods: In this study, we evaluated the therapeutic efficacy of EHS in a randomized controlled clinical trial with a 3-month follow-up. Totally, 70 patients with persistent HR-HPV infection were randomly assigned to receive intravaginal administration of EHS or placebo. HPV DNA, ThinPrep cytologic test (TCT), colposcopy, and safety evaluation were carried out after treatment. Microarray analysis was performed to compare transcriptome profiles before and after EHS treatment. A K14-HPV16 mouse model was generated to confirm the efficiency of EHS., Results: After 3 months, 74.3% (26/35) of the patients in the treatment group were HPV negative, compared to 6.9% (2/29) in the placebo group. High-throughput microarrays revealed distinct transcriptome profiles after treatment. The differentially expressed genes were significantly enriched in complement activation, immune response, and apoptotic processes. The K14-HPV16 mouse model also validated the remarkable efficacy of EHS., Conclusion: This study demonstrated that EHS is effective against HR-HPV infection and cervical lesions. Additionally, no obvious systemic toxicity was observed in patients during the trial. The superior efficacy and safety of EHS demonstrated its considerable value as a potential cost-effective drug for the treatment of HPV infection and HPV-related cervical diseases., (© 2024. Huazhong University of Science and Technology.)

The prognosis of patients with human papillomavirus (HPV)‑negative cervical cancer is significantly worse than that of patients with HPV‑positive cervical cancer. Understanding the mechanisms of this is crucial for preventing disease evolution. In the present study, the GV367‑snail family transcriptional repressor 2 (SNAI2) lentiviral vector was constructed and transduced into C‑33A cells. Subsequently, the proliferation of tumor cells was detected using the Cell Counting Kit (CCK)‑8 method. Flow cytometry was used to analyze the cell cycle progression of tumor cells. The glucose consumption of tumor cells was detected using an oxidase assay, and the senescence of tumor cells was detected using beta‑galactosidase staining. The gene expression and the activity of p38 and ERK1/2 were detected using reverse transcription‑quantitative PCR and western blotting, respectively. The C‑33A‑SNAI2 cell line was successfully established. Compared with HeLa and C‑33A‑Wild cells, the proliferation and percentage of G0/G1‑phase cells in the C‑33A‑SNAI2 group were decreased, as detected by the CCK‑8 assay (100±0 vs. 239.1±58.3 vs. 39.7±20.1, P<0.01) and flow cytometry (34.0±7.1% vs. 46.2±10.6% vs. 61.3±5.3%, P<0.05). Compared with the HeLa group, the glucose consumption of the C‑33A‑Wild and C‑33A‑SNAI2 groups was significantly decreased (P<0.01). The results of beta‑galactosidase staining showed that the proportion of beta‑galactosidase‑positive cells in the C‑33A‑SNAI2 group was significantly decreased compared with the C‑33A‑Wild group (P<0.01). Upregulation of SNAI2 enhanced the increase in p21 expression, and the decrease in CDK1, urokinase plasminogen activator receptor (u‑PAR) and cyclin D1 expression in C‑33A cells compared with C‑33A‑Wild cells (P<0.05). In addition, the activities of p38, ERK1/2 and the phosphorylated (p)‑ERK1/2/p‑p38 ratio were decreased in the C‑33A‑SNAI2 group compared with the C‑33A‑Wild and HeLa groups (P<0.05). In conclusion, SNAI2 enhanced HPV‑negative cervical cancer C‑33A cell dormancy, which was characterized by G0/G1 arrest, by the downregulation of u‑PAR expression, and a decrease in the activity of the p‑ERK1/2 and p‑p38MAPK signaling pathways in vitro . Cancer recurrence and metastases are responsible for most cancer‑related deaths. Given that SNAI2 is required for enhancing HPV‑negative cervical cancer cell dormancy, regulating this process may promote cervical tumor cells to enter a continuous dormant state, which could be a potential approach for tumor therapy.

With the knowledge of female reproductive tract microbiota gradually increasing, the connection between vaginal microbiota (VMB) and its related diseases is increasingly highlighted. Manifestation of VMB keeps changing with various dominated bacteria, which can affect the immune response of mucosal barrier and the entrance of pathogens. Human papillomavirus (HPV), as an oncogenic virus, is closely related to viral-associated cancer, such as cervical cancer. According to HPV infection status, VMB can transform into different types, and result in accelerating or restraining the progression of diseases, which have exposed the inner link between VMB and HPV. Therefore, probiotics therapy promises to be a new complementary therapy to rebuild a healthy VMB for patients, but there's still a long way to go before its ready for the clinic. This review focuses on composition, immune response, and application of VMB in HPV and its associated diseases and aims to provide the new ideas and directions for the research on VMB., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Aims: To assess colposcopic performance and determine indicators for competency within the new Australian primary human papillomavirus (HPV) cervical screening program., Materials and Methods: A retrospective observational study of 4542 women seen at The Royal Women's Hospital Colposcopy Clinic in Melbourne, from 1 December 2017 to 31 July 2020 after a higher-risk cervical screening test (CST) result., Results: Histological CIN2+ was detected in 25.1% up to two years from first colposcopy visit (FCV). The majority (86.7%) of CIN2+ was detected early within the first six months of presentation. Biopsy rate overall was 96.1% with abnormal colposcopic impression. Of four colposcopists with a lower biopsy rate, only one was able to achieve this early detection rate. Biopsy was also taken in over 30% of cases with negative reflex cytology and normal colposcopy, with CIN2+ detected in 5.0% among positive HPV16/18 and 3.8% with non-16/18 HPV. Positive predictive value of high-grade colposcopic impression at FCV averaged 66.4% (range: 54.9-81.6% among our colposcopists) and is poorly correlated with early detection rate of CIN2+. Overall accuracy of colposcopy is 84.5% (range: 78.7-90.3%), buoyed by high true negative colposcopic predictions secondary to high rates of negative reflex cytology referral with the new screening algorithm and is also unlikely to be a useful colposcopy indicator., Conclusions: Early detection rate of CIN2+ within the first six months of presentation is a useful measure of colposcopy competency and we would encourage our National Cancer Screening Register to explore this with the participating colposcopists., (© 2024 Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Cervical cancer (CC) screening in women comprises human papillomavirus (HPV) testing followed by cytology triage of positive cases. Drawbacks, including cytology's low reproducibility and requirement for short screening intervals, raise the need for alternative triage methods. Here we used an innovative triage technique, the WID-qCIN test, to assess the DNA methylation of human genes DPP6, RALYL and GSX1 in a real-life cohort of 28,017 women aged ≥30 years who attended CC screening in Stockholm between January and March 2017. In the analysis of all 2,377 HPV-positive samples, a combination of WID-qCIN (with a predefined threshold) and HPV16 and/or HPV18 (HPV16/18) detected 93.4% of cervical intraepithelial neoplasia grade 3 and 100% of invasive CCs. The WID-qCIN/HPV16/18 combination predicted 69.4% of incident cervical intraepithelial neoplasia grade 2 or worse compared with 18.2% predicted by cytology. Cytology or WID-qCIN/HPV16/18 triage would require 4.1 and 2.4 colposcopy referrals to detect one cervical intraepithelial neoplasia grade 2 or worse, respectively, during the 6 year period. These findings support the use of WID-qCIN/HPV16/18 as an improved triage strategy for HPV-positive women., (© 2024. The Author(s).)

The ectopic expression of cellular retinoic acid binding protein 2 (CRABP2) is associated with various tumorigenesis. However, the effects of CRABP2 on the progression of cervical cancer are still unclear. The current study aimed to investigate the role of CRABP2 in the malignant phenotypes of cervical cancer cells. CRABP2 was artificially regulated in CaSki, SiHa, and C-33A cells. CCK-8 assay and flow cytometry were used to assess the cell proliferation and apoptosis abilities, respectively. Wound healing assay and transwell assay were employed to measure the cell migration and invasion abilities, respectively. The results showed that CRABP2 was highly expressed in cervical carcinoma tissues and cell lines, and its high expression was associated with poor overall survival. Knockdown of CRABP2 promoted the cell apoptosis and inhibited cell proliferation, migration, and invasion in cervical carcinoma cells, whereas CRABP2 overexpression exhibited the opposite results. Mechanically, CRABP2 silencing suppressed the Integrin β1/FAK/ERK signaling via HuR. Treatment with siITGB1 or a FAK inhibitor PF-562271 or an ERK inhibitor FR180204 reversed the promoting effects of CRABP2 on cell proliferation, migration, and invasion. Moreover, the overexpression of CRABP2 reverted the HPV16 E6/E7 knockdown-induced inhibition of cell proliferation, migration, and invasion in cervical cancer cells. These results suggested that HPV16 E6/E7 promoted the malignant phenotypes of cervical cancer by upregulating the expression of CRABP2. In conclusion, CRABP2, upregulated by HPV E6/E7, promoted the progression of cervical cancer through activating the Integrin β1/FAK/ERK signaling pathway via HuR., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Around 70% of vaginal cancers and 40-50% of vulvar cancers are attributable to human papillomavirus (HPV). Globally the burden of these diseases is estimated to grow due to the increasing HPV prevalence and rapidly aging global population. We aimed to examine if HPV screening for cervical cancer has an additional beneficial effect in preventing vaginal and vulvar cancers. To assess this, we used long-term follow-up data from the Finnish randomized HPV screening trial., Methods: Between 2003 and 2008, over 236,000 women were individually randomized (1:1) to primary HPV or cytology screening in Southern Finland. We followed this cohort up to the year 2020. To compare the study arms, we calculated site-specific and pooled incidence rate ratios (IRRs) and mortality rate ratios (MRRs) for vaginal and vulvar cancers using Poisson regression., Results: During 3,5 million person-years of follow-up, the IRR for vaginal cancer in the HPV arm compared to the cytology arm was 0.40 (95% CI 0.17-0.88) and the corresponding MRR was 0.74 (95% 0.21-2.24). The corresponding IRR for vulvar cancer was 0.73 (95% 0.50-1.08) and the MRR was 0.64 (95% 0.23-1.62). The pooled IRR was 0.67 (95% 0.47 ̶ 0.95) and MRR 0.67 (95% 0.31 ̶ 1.37)., Conclusion: We found lower incidence of vaginal cancers with HPV screening compared to cytology screening. To validate our results, we recommend analyzing data on vaginal and vulvar cancers also from other HPV screening studies., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:, (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Human papillomavirus (HPV) is a major cause of cervical cancer. As the natural history of HPV-associated cervical lesions is HPV genotype-dependent, it is important to understand the characteristics of these genotypes and to manage them accordingly. Among high-risk HPVs, HPV16 and 18 are particularly aggressive, together accounting for 70% of HPV genotypes detected in cervical cancer. Other than HPV16 and 18, HPV31, 33, 35, 45, 52, and 58 are also at a high risk of progression to cervical intraepithelial neoplasia (CIN)3 or higher. Recent studies have shown that the natural history of HPV16, 18, 52, and 58, which are frequently detected in Japan, depends on the HPV genotype. For example, HPV16 tends to progress in a stepwise fashion from CIN1 to CIN3, while HPV52 and 58 are more likely to persist in the CIN1 to CIN2 state. Among the high-risk HPVs, HPV18 has some peculiar characteristics different from those of other high-risk HPV types; the detection rate in precancerous lesions is much lower than those of other high-risk HPVs, and it is frequently detected in highly malignant adenocarcinoma and small cell carcinoma. Recent findings demonstrate that HPV18 may be characterized by latent infection and carcinogenesis in stem cell-like cells. In this context, this review outlines the natural history of HPV-infected cervical lesions and the characteristics of each HPV genotype., (© 2024 The Author(s). Journal of Obstetrics and Gynaecology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Obstetrics and Gynecology.)

Cervical cancer, caused due to oncogenic types of human papillomavirus (HPV), is a leading preventable cause of cancer morbidity and mortality globally. Chronic, persistent HPV infection-induced cervical precursor lesions, if left undetected and untreated, can progress to invasive cancer. Cervical cancer screening approaches have evolved from cytology (Papanicolaou test) to highly sensitive HPV-based molecular methods and personalized, risk-stratified, management guidelines. Innovations like self-collection of samples to increase screening access, innovative triage methods to optimize management of screen positives, and scalable and efficacious precancer treatment approaches will be key to further enhance the utility of prevention interventions., Competing Interests: Disclosure The Author has no financial conflicts of interest to disclose. The opinions expressed by the Author are his own and this material should not be interpreted as representing the official viewpoint of the U.S. Department of Health and Human Services, the National Institutes of Health, or the National Cancer Institute., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: High-risk human papillomavirus (hrHPV)-based cervical cancer screening in the Netherlands led to a substantial increase in number of colposcopy referrals and low-grade lesions detected. Genotyping strategies may be employed to lower the screening-related burden., Methods: We evaluated 14 triage strategies with genotyping (HPV16/18 or HPV16/18/31/33/45/52/58) for hrHPV-positive borderlineormilddyskaryosis (BMD)ornormal cytology,usingdata from a population-based hrHPV-based screening trial with 5-year interval (POBASCAM). We considered colposcopy referral at baseline, after 6-month repeat cytology and after 5-year hrHPV testing. Performance was evaluated by one-round positive and negative predictive value (PPVandNPV) for CIN3+ and by two-roundcolposcopy referral rate. To identify efficient strategies, they were ordered by the one-round colposcopy referral rate. Adjacent strategies were compared by the marginal PPV for detecting one additional CIN3+ (mPPV)., Results: The most conservative strategy (repeat cytology after BMD and HPV16/18/31/33/45/52/58-positive normal cytology, next round otherwise) yielded an mPPV of 28%, NPV of 98.2%, and two-round colposcopy referral rate of 47.2%. Adding direct referral after BMD or genotype-positive BMD yielded an mPPV ≤ 8.2%, NPV ≥ 98.5% and an increase in colposcopy referral rate of 1.9% to 6.5%. Adding direct referral after HPV16/18-positive normal cytology yielded an mPPV ≤ 3.5%, NPV ≥ 99.5% and an increase in colposcopy referral rate of 13.9%., Conclusions: Direct colposcopy referral of women with BMD or normal cytology is unlikely to be efficient, but genotype-guided direct referral after BMD may be considered because the increase in colposcopies is limited., Impact: hrHPV screening programs can become very efficient when immediate colposcopy referral is limited to women at highest CIN3+ risk. See related In the Spotlight, p. 979., (©2024 American Association for Cancer Research.)

Objectives: Histopathological diagnosis of colposcopically identified cervical lesions is a critical step for the recognition of cervical cancer precursors requiring treatment. Although there have been efforts to standardize the histologic diagnosis of cervical biopsy specimens, in terms of terminology and use of biomarkers, there is no uniform approach in the pathology community. Adjunctive p16 immunohistochemistry (IHC) can highlight precancer diagnoses, with use recommendations outlined by the Lower Anogenital Squamous Terminology project., Methods: We assessed the diagnostic reproducibility of cervical histopathological biopsy specimens with and without p16 staining among 2 expert pathologists., Results: Interpretation of p16 IHC as positive vs negative was highly reproducible (92.5% agreement, κ = 0.85); greater variation was seen in the choice of which biopsy specimens required adjunctive p16 staining (78.0% agreement, κ = 0.43). Adjunctive p16 IHC did not significantly increase diagnostic agreement under multitiered grading systems (benign vs cervical intraepithelial neoplasia [CIN] 1/low-grade squamous intraepithelial lesion vs atypical squamous metaplasia vs CIN2/high-grade squamous intraepithelial lesion [HSIL] vs CIN3/HSIL-CIN3 vs cancer) (65.5% agreement, κ = 0.56 without p16; 70.0% agreement, κ = 0.58 with p16). However, when dichotomizing diagnoses based on clinical management (less than HSIL vs HSIL+), diagnostic agreement increased with p16 IHC (90.5% agreement, κ = 0.79 without p16; 92.0% agreement, κ = 0.84 with p16). For biopsy specimens taken from women positive for human papillomavirus (HPV) type 16, agreement was similar with or without adjunctive p16 (κ = 0.80 without p16; κ = 0.78-0.80 with p16). In contrast, p16 IHC substantially improved diagnostic agreement for cervical biopsy specimens taken from women positive for other high-risk HPV strains, producing improvements in κ from 0.03 to 0.24., Conclusions: Adjunctive p16 immunostaining provides useful information in the evaluation of cervical biopsies for precancer. In our study, we have demonstrated that it is highly reproducible between 2 pathologists, although the decision of which biopsies warrant its use is less so. Furthermore, although p16 IHC showed a limited increase in diagnostic reproducibility for all biopsies included in our study, it did demonstrate a more sizable gain in biopsies negative for HPV 16 but positive for other high-risk genotypes. Further studies are needed to clarify the role of p16 IHC and how it can be optimized for the detection of cervical precancer, particularly in HPV-vaccinated populations where types other than HPV 16 are relatively more important., (© American Society for Clinical Pathology, 2024.)

High-risk human papillomavirus (hrHPV) infection is associated with cervical cancer; imbalanced vaginal microecology may contribute to HPV progression. Currently used methods for clinical vaginal-microecology (CVM) testing are associated with several disadvantages, such as low accuracy and complicated operation. This retrospective study presents a novel testing method to examine vaginal microecology via double-fluorescence staining and explores the relationship between hrHPV and CVM. We analyzed 1242 patients who underwent hrHPV testing at our hospital over a two-month period; of these, 695 also underwent clinical vaginal-microecology testing (CVMT). Patients underwent routine leukorrhea detection (n=322), functional testing (n=277), and our novel double-fluorescence staining-based CVMT approach (n=376). Patients with hrHPV exhibited more epithelial cells, miscellaneous bacteria, and hyphae than those without hrHPV on double-fluorescence staining-based CVMT approach. Double-fluorescence staining was effective in identifying indicators of hrHPV infection and may serve as an auxiliary tool for clinical hrHPV screening., Competing Interests: Declaration of competing interest The author reports no conflicts of interest in this work., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: High-risk human papillomavirus (HR-HPV) is a known cause of cervical cancer (CC). Latvia has a high incidence of CC compared with the average incidence in the European Union. This study aims to fill the data gap on the HR-HPV burden in Latvia, providing information on its prevalence and associated factors., Methods: The cross-sectional study was conducted from February 2021 to April 2022. Participants 25-70 years old visiting a general practitioner (general population) or those referred to a colposcopy clinic with changes in their cervical cytology (colposcopy population) collected vaginal self-sample and completed a paper-based questionnaire. Samples were analyzed with Cobas 6800 System (Roche) for HPV16, HPV18 and other HR-HPV (HPV31/33/35/39/45/51/52/56/58/59/66/68). Descriptive statistics for categorical variables were performed. The Chi-square test was used to determine for the statistical significance of differences in the proportions of the dependent variable between subgroups of the independent variable. Univariate and multivariate binary logistic regression were used to identify factors associated with positive HR-HPV status. Results were considered statistically significant at P < 0.05., Results: A total of 1274 participants provided a valid sample. The prevalence of any HR-HPV infection was 66.8% in the colposcopy group and 11.0% in the general population. Factors associated with positive HR-HPV status were marital status single/divorced/widowed (vs. married/cohabiting) [adjusted OR (aOR) 2.6; P = 0.003], higher number of lifetime sex partners [aOR 5.1 (P < 0.001) and 4.0 (P = 0.001)] for six or more and three to five partners in the general population; in the colposcopy group, the statistical significance remained only for Latvian ethnicity (vs. other) (aOR 1.8; P = 0.008) and current smoking (vs. never) (aOR 1.9; P = 0.01)., Conclusion: We documented a comparison to European Union HR-HPV infection burden in Latvia. Any HR-HPV positivity was significantly associated with sexual and other health behavior., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Public Health Association.)

Human papillomavirus (HPV) infection is a sexually transmitted infection which causes cancer, especially cervical cancer. HPV infection and cervical cancer are a public health concern in South Africa. Primary prevention interventions, such as vaccination against cervical cancer, have been rolled out in the country. However, the uptake of the vaccine faces challenges due to various factors. The aim of the review was to identify factors which influence the uptake of the vaccine. A six-step framework developed by Levac, Colquhon and O'Brien was adopted to guide this scoping review. The articles were searched in the following databases: EBSCOhost, PubMed, CINAHL and Google scholar. The search, conducted from May to July 2023 was limited to articles published in English between 2008-2023 and those conducted in Africa. The results showed that most studies were conducted in sub-Saharan Africa, with majority of the studies being from Nigeria. Subthemes were extracted from the articles and categorised under the four themes of the Social Ecological Model. The four themes used from the Social Ecological Model were individual factors; interpersonal factors; community and societal factors, and organisational factors and public policy. The subthemes were socioeconomic and sociodemographic of parents, knowledge, fear and mistrust, family structure and proximity to cancer/STI, misinformation from social media, religion, culture and tradition, free vaccination programme and lack of engagement. The identified gap in literature was a lack of studies of factors which influence HPV vaccination uptake in South Africa and qualitative studies that explore and provide the factors influencing uptake. We conclude that in designing effective interventions for the uptake of HPV vaccines, it is important to consider influential factors that are tailor-made for specific demographics., Competing Interests: The Authors declared no conflict of interest, (African Journal of Reproductive Health © 2024.)

Objective: The objective of the study is to validate a new human papillomavirus (HPV) L1 high-risk specific serological assay in a case-control study. Methods: Serum samples of 138 patients (cervical intraepithelial neoplasia (CIN) 1, 2, and 3 and cervical cancer), 21 vaccinees, and 246 female controls were tested for the presence of HPV L1 high-risk specific antibodies. Results: HPV L1 high-risk antibodies were detected in 100% of the CIN1 and 2, 86.6% of the CIN3 and 82.4% of the cervical cancer cases, 100% of the vaccinees, and 3.9% of the female controls. Area under the curve (AUC) was calculated with 0.91 for controls versus CIN2+, 0.923 for controls versus CIN1+, and 0.968 for controls versus CIN1/2. Conclusion: The HPV L1 high-risk specific serological lateral flow rapid test shows promising data in the field of early detection of HPV high-risk induced cervical cancer and its precursor lesions. This easy-to-use, robust, and affordable approach could offer a chance to reach women in low- or middle-income countries (LMICs) that could not be reached by HPV molecular testing-based cervical cancer screening programs., Competing Interests: RH is an inventor of the CER818 assay and shareholder of Abcerion Diagnostics. AR has received lab equipment from Euroimmun and consulting fees and/or honoraria for lectures, presentations, speakers, etc., by Roche, Astra Zeneca, Pfizer, Celgen, Eisai, Novartis, MSD, Hexal, Amgen, Exact Sciences, Pierre Fabre, Gilead, and Lilly., (Copyright © 2024 Karen Bräutigam et al.)

The present study was aimed at showing the importance of HPV DNA status and the clinical history of the patients required by the cytologist for accurate reporting. A total of 1250 symptomatic women who attended the gynaecology outpatient department of the Mahavir Cancer Sansthan and Nalanda Medical College, Patna, for pap smear examinations were screened and recruited for the study. Due to highly clinical symptoms out of the negative with inflammatory smears reported, one hundred and ten patients were randomly advised for biopsy and HPV 16/18 DNA analysis by a gynaecologist to correlate negative smears included in the study. Pap smear reports revealed that 1178 (94.24%) were negative for intraepithelial lesions (NILM) with inflammatory smears, 23 (1.84%) smears showed low-grade squamous intraepithelial lesions (LSIL), 12 (0.96%) smears showed high-grade squamous intraepithelial lesions, and 37 (2.96%) smears showed an atypical squamous cell of undetermined significance (ASC-US). A biopsy of 110 out of 1178 (NILM) patients revealed that 15 (13.63%) women had cervical cancer, 29 women had CIN I, 17 women had CIN II + CIN III, 35 women had benign cervical changes, and 14 women had haemorrhages. On the other hand, HPV 16/18 DNA was detected as positive in 87 out of 110. The high positivity of HPV in biopsied cases where frank cervical cancer and at-risk cancer were also observed in the negative smear-screened patients reveals that the HPV status and clinical history of the patients will be quite helpful to the cytologist for accurate reporting, and suggests that a negative HPV DNA result may be a stronger predictor of cervical cancer risk than a negative Pap test., (© 2024. The Author(s).)

Background: In China, the national cervical cancer screening protocol involves initial testing for high-risk human papillomavirus (hrHPV), followed by cytology for hrHPV-positive cases. This study evaluates the effectiveness of PAX1 methylation (PAX1 m ) analysis in identifying precancerous or cancerous lesions in cervical samples from Chinese women positive for non-16/18 hrHPV strains., Methods: Between February 2022 and March 2023, 281 cervical samples from non-16/18 hrHPV-positive women underwent cytological examination and PAX1 m analysis. The study assessed the statistical relationship between PAX1 m levels and the presence of cervical lesions, comparing the diagnostic performance of PAX1 m to conventional cytology., Results: A significant association was found between PAX1 methylation levels and the risk of CIN2 + and CIN3 + lesions, with 47 instances of CIN2 + detected. Odds ratios (ORs) for moderate and high PAX1 m levels were 8.86 (95% CI: 2.24-42.17) and 166.32 (95% CI: 47.09-784.97), respectively. The area under the ROC curve for PAX1 m in identifying CIN2 + lesions was 0.948 (95% CI: 0.895-0.99). PAX1 m demonstrated similar sensitivity and negative predictive value (NPV) to cytology but reduced the colposcopy referral rate from 47.7% with cytology alone to 25.6% with PAX1 m , showing superior specificity and positive predictive value across age groups., Conclusions: PAX1 methylation is a strong indicator of CIN2 + and CIN3 + risk, offering diagnostic performance comparable to cytology with the added benefit of reduced unnecessary colposcopy referrals. These findings support the use of PAX1 m analysis as a reliable tool for triaging non-16/18 hrHPV-positive women in outpatient settings., (© 2024. The Author(s).)

Cervical cancer is one of the most common malignant tumours. Human papillomavirus (HPV) infection is the main cause of this cancer so that it could be prevented by screening and early treatment. Developing reginal screen protocols of maximum public health efficacy requires in-depth understandings of local HPV distribution and consequential cancer risks. Therefore, test results of HPV genotyping, cytology testing (TCT) and colposcopy inspection with biopsy were collected in this retrospective research. Data included by this research involved 63,906 women received screen related tests from Shenzhen Baoan Shiyan People's Hospital and the subsidiary institutes between 2017.01 and 2023.05. 10,238 colposcopies were performed in this period collecting 8,716 samples and 814 high-grade CIN were discovered. Within the 763 high-grade CIN cases with both TCT and HPV testing results, 232 were tested cytologically normal but only 30 were negative in HPV test. Besides, the rates of high-grade CIN observed in coinfection were all lower than the estimated rates generated from related single infection. HPV 52, 58 and 16 were found to be the most common types in Baoan, Shenzhen. The result also suggested that HPV coinfections should not increase risk for cervical cancers., (© 2024. The Author(s).)