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Simple Summary: Cervical intraepithelial neoplasia grade 2-3 (CIN2-3) is often treated by large loop excision of the transformation zone (LLETZ) to prevent invasive cervical cancer. However, there is a high risk of persistent/recurrent CIN2-3 and cervical cancer for up to 20 years post-treatment. Factors such as high-risk human papillomavirus (HR-HPV) and surgical margins influence this risk. Clinicians using LLETZ aim to achieve clear surgical margins while minimizing the volume of tissue removal and side effects. This retrospective study assessed the roles of HR-HPV status post-LLETZ, surgical margins, and LLETZ characteristics (excision type, cone volume, and dimensions [length, thickness, and circumference]) for long-term reassurance against persistent/recurrent CIN2-3 in a large population spanning 25 years. We showed greater reassurance associated with negative HR-HPV post-LLETZ and clear surgical margins, but not with LLETZ characteristics, although cone length and type 3 excision correlated with clear margins. These findings provide valuable insights into long-term outcomes that may help optimize LLETZ. Background/Objective: Women treated with large loop excision of the transformation zone (LLETZ) for cervical intraepithelial neoplasia grade 2-3 (CIN2-3) remain at risk of CIN2-3 and cervical cancer for many years. We assessed the roles of high-risk human papillomavirus (HR-HPV) post-LLETZ, surgical margins, and LLETZ characteristics on the long-term risk of CIN2-3. Methods: A retrospective observational study was performed using data for 432 women with a histological diagnosis of CIN2-3 treated by LLETZ between 1996 and 2020 and followed-up until October 2021 at Hospital Bellvitge in Barcelona, Spain. Age, surgical margins, 6-month HR-HPV status, excision type, and cone volume/dimensions were analyzed in association with the risk of persistent/recurrent CIN2-3. The cumulative probability of persistent/recurrent CIN2-3 was calculated using the Kaplan–Meier and Cox models. Results: Persistent/recurrent CIN2-3 was detected in 7.4%, with over 90% found within 5 years post-LLETZ. Predictors of persistent/recurrent CIN2-3 were HR-HPV (HR = 7.36, 95% CI = 3.55–15.26), involved margins (HR = 3.94, 95% CI = 1.68–9.25), uncertain margins (HR = 4.42, 95% CI = 1.55–12.55), and age ≥ 35 years (HR = 2.92, 95% CI = 1.19–7.13). Type 3 excision (p = 0.035) and cone length (p = 0.010) correlated with clear margins. The negative predictive value (NPV) of both negative HR-HPV and clear margins post-LLETZ was 98.7%. Conclusions: The combination of negative HR-HPV and clear margins post-LLETZ provides stronger reassurance against the risk of persistent/recurrent CIN2-3 than do LLETZ characteristics. However, larger excisions in older women likely reduce the risk of involved margins. Close surveillance, including repeat HR-HPV testing in the first 5 years post-LLETZ, is crucial. [ABSTRACT FROM AUTHOR]

Abstract Objective To assess the clinical value of DNA methylation measurement in exfoliated cervical cells for distinguishing high-grade squamous intraepithelial lesions (HSIL) from other cervical abnormalities. Methods A total of 276 patients were enrolled, and general clinical information was collected. Exfoliated cervical cells were obtained to assess human papillomavirus (HPV) infection, conduct ThinPrep cytology tests (TCT), and measure methylation levels of JAM3 (△CtJ) and PAX1 (△CtP). Logistic regression was performed to identify factors significantly associated with HSIL diagnosis. A conditional inference tree model and the area under the curve (AUC) were employed to evaluate the efficacy of JAM3 and PAX1 methylation in detecting HSIL. Results Independent risk factors for HSIL diagnosis included △CtJ, △CtP, atypical squamous cells of undetermined significance (ASCUS), and HPV16 infection. The conditional inference tree indicated that 96.4% of patients were non-HSIL when △CtJ > 11.66, and 99.1% were non-HSIL when △CtP > 10.97. The diagnostic performance of △CtJ/△CtP surpassed that of TCT/HPV alone. Among six methods, the combination of △CtP, TCT, and high-risk HPV (hr-HPV) testing achieved the highest sensitivity (91.2%), positive predictive value (50.0%), negative predictive value (98.6%), and AUC (0.932). Conclusion In women with hr-HPV infection, DNA methylation analysis of cervical cytology outperformed traditional TCT or HPV testing. The combination of △CtP with TCT and HPV may offer the most accurate screening approach for HSIL.

Xue Bai,1 Ya-Kun Liu,1 Ya-Jing Jia,1 Dao-Juan Li,2 Nai-Yi Du1 1Department of Gynecology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, 050011, People’s Republic of China; 2Cancer Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, 050011, People’s Republic of ChinaCorrespondence: Nai-Yi Du, Department of Gynecology, The Fourth Hospital of Hebei Medical University, 12 Jiankang Road, Shijiazhuang, Hebei Province, 050011, People’s Republic of China, Tel +8618531116751, Email dunaiyiyi@outlook.comBackground: Although both cervical intraepithelial neoplasia (CIN) II and CIN III carry the potential to progress into cervical cancer, to date, an optimal screening method for CIN2+ (CIN II, CIN III, and cervical cancer) cervical lesions is yet to be established.Methods: In this retrospective study, data from 2035 patients treated at the Fourth Hospital of Hebei Medical University between 2019 and 2021 were analyzed. The screening efficacy of three methods—the ThinPrep cytologic test (TCT) alone, the high-risk-human papillomavirus (HR-HPV) test alone, and the combined TCT and HR-HPV screening for CIN2+ lesions—were assessed using cervical histopathology as the reference standard. Additionally, correlations between HPV16 cycle threshold (Ct) values, HPV18 Ct values, and the severity of cervical lesions were analyzed. Receiver operating characteristic (ROC) curves were plotted to evaluate the diagnostic utility of HPV16 Ct values for CIN2+ lesions.Results: Compared with TCT or HR-HPV testing alone, the combined TCT and HR-HPV test had the highest sensitivity of 98.1% (P < 0.0001), the highest negative predictive value of 99.8% (P = 0.0001), and the lowest missed diagnosis rate of 1.9% (P < 0.0001) for screening CIN2+ lesions. Additionally, the combined test yielded the largest area under the ROC curve (AUC) value of 0.9480. There was a significant difference in HPV16 Ct values for various degrees of cervical lesions (P < 0.001), with the Spearman rank correlation test revealing a significant negative correlation (rs = − 0.447, P < 0.001). The optimal HPV16 Ct value for diagnosing CIN2+ lesions was 29.995, with an AUC of 0.797 (P < 0.0001).Conclusion: The combination of TCT and HR-HPV testing was the most effective method for screening CIN2+ lesions. Furthermore, HPV16 Ct values were negatively correlated with the severity of cervical lesions, with a threshold of 29.995 potentially indicating the presence of CIN2+ lesions.Keywords: CIN2+ cervical lesions, cervical cancer, combined test, HPV16 Ct value, HR-HPV, TCT

Abstract Background High-risk genotypes of Human Papillomavirus are responsible for 90% of cases of cervical cancer worldwide. Inflammation of squamous cells is mainly linked to HPV. In Gabon, HPV is endemic and circulates among the female population. The study aimed to determine the prevalence of HR-HPV genotypes and to investigate the correlation between squamous cell inflammation and HPV viral load in infected women in Gabon. Methods The cross-sectional study was conducted at Libreville University Hospital Center (UHC) and National Public Health Laboratory from March to May 2024 among 399 women. Two cervical smears were taken. Genotype detection was carried out by multiplex fluorescence real-time PCR in the NPHL virology unit. Cytology was carried out in UHC’s anatomic-pathology laboratory. Data were analyzed by SPSS software. Graphs were plotted using Microsoft Excel 2016. Results The prevalence of Human Papillomavirus was 26.1% (95% CI: 22-30.6). The prevalence of HR-HPV genotypes was 24.8%. The most common HR-HPV genotypes were HPV-16/52/18/35/56/58/53/68. The rate of multiple HPV infections was 29.8% and 95.2% for the HR-HPV infection rate. Viral load was significantly correlated with squamous cell inflammation (r = 0.977 and P = 0.001). Conclusion HR-HPV infection remains a concern in women, however early screening is necessary for optimal monitoring and management. HR-HPV viral load is a predictive marker of squamous cell inflammation.

Objective: To assess the clinical value of DNA methylation measurement in exfoliated cervical cells for distinguishing high-grade squamous intraepithelial lesions (HSIL) from other cervical abnormalities. Methods: A total of 276 patients were enrolled, and general clinical information was collected. Exfoliated cervical cells were obtained to assess human papillomavirus (HPV) infection, conduct ThinPrep cytology tests (TCT), and measure methylation levels of JAM3 (△CtJ) and PAX1 (△CtP). Logistic regression was performed to identify factors significantly associated with HSIL diagnosis. A conditional inference tree model and the area under the curve (AUC) were employed to evaluate the efficacy of JAM3 and PAX1 methylation in detecting HSIL. Results: Independent risk factors for HSIL diagnosis included △CtJ, △CtP, atypical squamous cells of undetermined significance (ASCUS), and HPV16 infection. The conditional inference tree indicated that 96.4% of patients were non-HSIL when △CtJ > 11.66, and 99.1% were non-HSIL when △CtP > 10.97. The diagnostic performance of △CtJ/△CtP surpassed that of TCT/HPV alone. Among six methods, the combination of △CtP, TCT, and high-risk HPV (hr-HPV) testing achieved the highest sensitivity (91.2%), positive predictive value (50.0%), negative predictive value (98.6%), and AUC (0.932). Conclusion: In women with hr-HPV infection, DNA methylation analysis of cervical cytology outperformed traditional TCT or HPV testing. The combination of △CtP with TCT and HPV may offer the most accurate screening approach for HSIL. [ABSTRACT FROM AUTHOR]

Background: Systematic study on the relationship between vaginal microbiota and high-risk human papillomavirus infection (HR-HPV) is limited. Hence, the aim of this study is to investigate the correlation between vaginal microbiota and HR-HPV infection through a meta-analysis of case-control studies. Methods: Chinese Journal Full-text database, Wanfang database, PubMed database, VIP Chinese Science and Technology Journal database, Web of Science, ScienceDirect, ProQuest, JSTOR, Wiley, and IEEE Xplore were synthetically searched for studies about the correlation between vaginal microbiota and HR-HPV infection. Revman 5.3 software was used to assess the relationship between vaginal microbiota and HPV infection through meta-analysis. Finally, forest map was used to calculate the results and funnel plot was applied to test the publication bias. Results: Fourteen independent studies were admitted in this study, containing a total of 21, 446 women in gynecological outpatients. Compared with HR-HPV negative group, the prevalence of bacterial vaginosis (BV) [odds ratio (OR)=2.45, 95% confidence intervals (CI): 1.83-3.27, P <0.00001], Ureaplasma urealyticum (UU) (OR=1.38, 95% CI: 1.23-1.54, P <0.00001), and Chlamydia trachomatis (CT) (OR=3.53, 95% CI: 2.82-4.41, P <0.00001) increased in HR-HPV positive group through meta-analysis, while, there was no significant difference in the prevalence of trichomonal vaginitis (TV) (OR=1.69, 95% CI: 0.97-2.96, P=0.06) and vulvovaginal candidiasis (VVC) (OR=0.91, 95% CI: 0.54-1.51, P=0.71. Conclusions: Vaginal pathogens are closely related to HR-HPV infection. When BV, UU, and CT are abnormal, the risk of HR-HPV infection is increased. [ABSTRACT FROM AUTHOR]

Cervical cancer is a largely preventable malignancy of the uterine cervix. The tendencies in cervical cancer morbidity and mortality have remained similar for the past decade, albeit with increasing frequency in low- and middle-income countries (LMICs). Moreover, in the majority of LMICs, cervical cancer is the second most prevalent cancer and the second most common cause of cancer-related death among reproductive-age women. High-risk human papillomavirus (HR-HPV) infections have been proven to be associated with up to 95% of cervical cancer cases, with HPV-16 and HPV-18 types being responsible for approximately 70% of all cervical cancers, with the other high-risk HPV types accounting for up to a further 25%. More recently, the latest data appear to confirm there is a change in the frequency of HR-HPV occurrence, especially HPV-16 and HPV-18, as a reflection of the implementation of preventive vaccination programs. Owing to the growing incidence of cervical cancer among reproductive-age women and with the development of cancer management approaches, fertility-sparing options have been proposed for early-stage cervical cancer management as an option for young women, especially those with unaccomplished reproductive desires. However, methods applied for this purpose (cold-knife conization, loop electrosurgical excision, trachelectomy) have variable outcomes and do not prevent risks of relapse. Multiple factors are involved in cervical cancer recurrence, even in cases treated at the early stage of the disease. In this review, the authors unveil whether HPV infection and virus type could be one of the key factors associated with cervical cancer recurrence after fertility-sparing surgery. Reviews of the literature reveal that recurrent and persistent HR-HPV infection is a strong predictor of cervical lesions' relapse. In particular, HPV-16 and HPV-18 infections and their persistence have been reported to be associated with cervical cancer recurrence. HR-HPV genotyping before and after fertility-sparing surgery for cervical cancer could facilitate a personalized approach and improve the overall survival rate. Screening for HR-HPV is essential during the follow-up of cervical cancer-treated women and will help to predict possible cancer recurrence. [ABSTRACT FROM AUTHOR]

Background: High-risk genotypes of Human Papillomavirus are responsible for 90% of cases of cervical cancer worldwide. Inflammation of squamous cells is mainly linked to HPV. In Gabon, HPV is endemic and circulates among the female population. The study aimed to determine the prevalence of HR-HPV genotypes and to investigate the correlation between squamous cell inflammation and HPV viral load in infected women in Gabon. Methods: The cross-sectional study was conducted at Libreville University Hospital Center (UHC) and National Public Health Laboratory from March to May 2024 among 399 women. Two cervical smears were taken. Genotype detection was carried out by multiplex fluorescence real-time PCR in the NPHL virology unit. Cytology was carried out in UHC's anatomic-pathology laboratory. Data were analyzed by SPSS software. Graphs were plotted using Microsoft Excel 2016. Results: The prevalence of Human Papillomavirus was 26.1% (95% CI: 22-30.6). The prevalence of HR-HPV genotypes was 24.8%. The most common HR-HPV genotypes were HPV-16/52/18/35/56/58/53/68. The rate of multiple HPV infections was 29.8% and 95.2% for the HR-HPV infection rate. Viral load was significantly correlated with squamous cell inflammation (r = 0.977 and P = 0.001). Conclusion: HR-HPV infection remains a concern in women, however early screening is necessary for optimal monitoring and management. HR-HPV viral load is a predictive marker of squamous cell inflammation. [ABSTRACT FROM AUTHOR]

ABSTRACT Persistent infection with high-risk human papillomavirus (HR-HPV) is the principal etiological factor of cervical cancer. Considering the gradual progression of cervical cancer, the early, rapid, sensitive, and specific identification of HPV, particularly HR-HPV types, is crucial in halting the advancement of the illness. Here, we established a rapid, highly sensitive, and specific HR-HPV detection platform, leveraging the CRISPR/Cas12a assay in conjunction with multienzyme isothermal rapid amplification. Our platform enables the detection and genotyping of 14 types of HR-HPV by using type-specific crRNAs. The outcomes of the detection can be interpreted either through a fluorescence reader or visually. Furthermore, we achieved one-tube multiplex detection of 14 HR-HPV types through the use of multiple amplifications and a crRNA pool. The detection sensitivity of this method is 2 copies/μL with no cross-reactivity, and the results can be obtained within 30 minutes. This method exhibited 100% clinical sensitivity and 100% clinical specificity when applied to 258 clinical specimens. Based on these findings, our CRISPR/Cas-based HR-HPV detection platform holds promise as a novel clinical detection tool, offering a visually intuitive and expedited alternative to existing HPV infection diagnostics and providing fresh perspectives for clinical cervical cancer screening.IMPORTANCEThis study developed a novel high-risk human papillomavirus (HR-HPV) detection platform based on CRISPR/Cas12a technology. This platform not only enables the rapid, highly sensitive, and specific detection and genotyping of 14 types of HR-HPV but also achieves single-tube multiplex detection of 14 HR-HPV types through ingenious design. The outcomes of the detection can be interpreted either through a fluorescence reader or visually. To the best of our knowledge, this is the first paper to utilize CRISPR/Cas diagnostic technology for the simultaneous detection of 14 types of HPV and to evaluate its feasibility in clinical sample detection using a large number of clinical samples. We hope that this work will facilitate the rapid and accurate detection of HPV and promote the broader application of CRISPR/Cas diagnostic technology.

In order to determine the significance of HR-HPV (high risk HPV, HR-HPV) E6/E7 mRNA detection for screening the severity of cervical cancer in relation to age, a total of 308 patients were admitted to the Department of Gynecology at The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical University between July 2017 and July 2018 and underwent LBC (Liquid Based Cytology) detection and HR-HPV E6/E7 mRNA detection. Data were then compared with the criteria laid down by the Pathology Department. The positive rate of HR-HPV E6/E7 mRNA detection was significantly higher in a CIN (cervical intraepithelial neoplasia) group than in a chronic cervicitis group. The sensitivity of LBC was higher than that for HR-HPV E6/E7 mRNA detection, while the specificity of LBC detection was higher than that of HR-HPV E6/E7 mRNA detection (p < 0.05). For women under 30 years old, the specificity of HR-HPV E6/E7 mRNA detection was lower than that of LBC detection, while the sensitivity of HR-HPV E6/E7 mRNA detection was higher than that of LBC detection. For women 30 years-of-age and above, the specificity of HR-HPV E6/E7 mRNA detection was significantly lower than that for LBC. HR-HPV E6/E7 mRNA detection has significant advantages for the screening of cervical cancer, especially in women under 30 years old. [ABSTRACT FROM AUTHOR]

Background: Qingdu Fang (QDF) is a traditional Chinese herbal formula with remarkable clinical effect in the treatment of HR-HPV, but its mechanism remains unclear. In this study, UPLC-QTOF-MS was used to detect its components, network pharmacology was used to explore the traditional Chinese medicine monomers and their related targets for the treatment of HR-HPV in QDF. Molecular docking and in vitro experiments were performed to verify the results. Methods: QDF constituents and active compounds were identified using UPLCQTOF-MS analysis. TCMSP and GeneCard databases were used to identify active components, targets, and potential therapeutic targets in HR-HPV. PPI network was constructed using the String database to analyze protein-protein interactions. Cytoscape3.7.2 was used to construct PPI networks, while GO enrichment and KEGG pathway analyses with R. The effect of QDF on H8 cell proliferation was measured using the CCK-8 method, and apoptosis and cell cycle was assessed with flow cytometry. The effects of QDF on PI3K/AKT pathway were detected by Western blotting. Results: A total of 27 compounds were identified on QDF by UPLC-QTOF-MS. Base on Network pharmacology, a total of 254 target genes are involved in the action of QDF on cervical HR-HPV. PPI analysis suggested that TP53, JUN, AKT1, STAT3, TNF and IL6 were potential targets for QDF treatment of HR-HPV. Molecular docking shows that two compounds have strong binding activity with AKT1. CCK-8 and morphological observation have shown that QDF inhibits H8 cell proliferation in a dose-dependent manner. Flow cytometry experiments suggest that QDF induces apoptosis and cell cycle arrest in H8 cells. Western blotting experiments reveal that QDF inhibits the PI3K/AKT signaling pathway. Conclusion: QDF has a multi-faceted therapeutic approach for HR-HPV, targeting inflammation, oxidation, and apoptosis. It induces apoptosis in H8 cells by inhibiting the PI3K/AKT pathway. [ABSTRACT FROM AUTHOR]

BackgroundSystematic study on the relationship between vaginal microbiota and high-risk human papillomavirus infection (HR-HPV) is limited. Hence, the aim of this study is to investigate the correlation between vaginal microbiota and HR-HPV infection through a meta-analysis of case-control studies.MethodsChinese Journal Full-text database, Wanfang database, PubMed database, VIP Chinese Science and Technology Journal database, Web of Science, ScienceDirect, ProQuest, JSTOR, Wiley, and IEEE Xplore were synthetically searched for studies about the correlation between vaginal microbiota and HR-HPV infection. Revman 5.3 software was used to assess the relationship between vaginal microbiota and HPV infection through meta-analysis. Finally, forest map was used to calculate the results and funnel plot was applied to test the publication bias.ResultsFourteen independent studies were admitted in this study, containing a total of 21, 446 women in gynecological outpatients. Compared with HR-HPV negative group, the prevalence of bacterial vaginosis (BV) [odds ratio (OR)=2.45, 95% confidence intervals (CI): 1.83-3.27, P

Abstract Introduction Long-term exposure to high-risk human papillomavirus (Hr-HPV) is a well-known necessary condition for development of cervical cancer. The aim of this study is to screen for Hr-HPV using vaginal self-sampling, which is a more effective approach to improve women’s adherence and increase screening rates. Methods This pilot study included a total of 100 Women living with HIV (WLWHIV), recruited from the Center for Listening, Care, Animation, and Counseling of People Living with HIV in Bamako. Hr-HPV genotyping was performed on Self-collected samples using the Cepheid GeneXpert instrument. Results The median age of WLWHIV was 44 (interquartile range [IQR], 37–50) years. Approximately 92% of the study participants preferred self-sampling at the clinic, and 90% opted to receive result notifications via mobile phone contact. The overall prevalence of Hr-HPV among study participants was 42.6%, and the most frequent Hr-HPV sub-types observed were HPV18/45 (19.1%), HPV31/35/33/52/58 (13.8%), and HPV39/68/56/66 (12.8%), followed by HPV16 (5.3%), and HPV51/59 (5.3%). WLWHIV under 35 years of age had a higher frequency of Hr-HPV compared to their older counterparts, with rates of 30% versus 11.1% (p = 0.03). The duration of antiretroviral treatment showed an inverse association with Hr-HPV negativity, with patients on treatment for 15 (IQR, 10–18) years versus 12 (IQR = 7–14) years for Hr-HPV positive patients (95% CI [1.2–5.8], t = 3.04, p = 0.003). WLWHIV with baseline CD4 T-Cell counts below 200 exhibited a higher frequency of Hr-HPV compared to those with baseline CD4 T-Cell counts above 200 (17.9% versus 1.9%, p = 0.009). However, other demographics and clinical factors, such as marital status, age of sexual debut, parity, education, history of abortion, history of preeclampsia, and cesarean delivery, did not influence the distribution of Hr-HPV genotypes. Conclusion Our findings indicate that WLWHIV under the age of 35 years old exhibited the highest prevalence of Hr-HPV infection, with HPV18/45 being the most prevalent subtype. Additionally, WLWHIV with baseline CD4 T-Cell counts below 200 showed the highest infection rates.

Context: CytoPath®Easy kit (DiaPath S.p.A.) offers a major advantage compared to other commercially available kits available for the screening of cervical cancer, as it does not require additional equipment for sample processing. Using this methodology, collected epithelial cells are immersed in a preservative liquid before setting as a thin layer on a slide via gravity sedimentation. Aims: To evaluate the suitability of the CytoPath®Easy kit for the processing of cervical samples, detection of pre-neoplastic lesions, and nucleic preservation and extraction for HR-HPV diagnosis. Materials and Methods: A total of 242 self-sampled cervical specimens were utilized, with 192 collected in CytoPath®Easy vials and 50 collected and processed using the ThinPrepTM for comparative analysis. The samples underwent processing, Papanicolaou staining, and microscopic evaluation for morphological parameters. The extracted nucleic acids were assessed for purity and integrity, and the detection of high-risk human papillomavirus (HR-HPV) was carried out using the Alinitym HR HPV system kit (Abbott Laboratórios Lda). Results: Both methods demonstrated effective performance, enabling the morphological assessment of the cervical epithelium. Statistical analysis indicated that ThinPrepTM yielded significantly better results in terms of cellularity. Conversely, CytoPath®Easy exhibited superior performance in terms of the quantity of extracted DNA and its degree of purification. Concerning the time consumed during processing, both methods were comparable, with the CytoPath®Easy methodology standing out for its cost-effectiveness, as it does not necessitate additional instruments and consumables. Conclusions: The novel CytoPath®Easy methodology proves effective in preserving both nucleic acids and cell morphology characteristics, two crucial features for cervical cancer screening.

Introduction: The role of multiple high‐risk human papillomavirus (HR‐HPV) infections on the occurrence of persistence/recurrence of high‐grade squamous intraepithelial lesion (HSIL) after conization/surgery for cervical intraepithelial neoplasia was evaluated. Material and methods: A systematic search of Pubmed/Medine, Scopus, Cochrane databases from inception to June 30, 2023 was performed. Three reviewers independently screened the abstracts of the selected studies and extracted data from full‐text articles. The data were subsequently tabulated and compared for consistency. The bias associated with each included study was evaluated according to the OSQE method. PROSPERO registration number CRD42023433022. Results: Out of 1606 records screened, 22 full text articles met the inclusion criteria. A total of 8321 subjects treated (loop electrosurgical excision, laser or surgery) because of HSIL were followed‐up and included in the meta‐analysis. The pooled prevalence of overall persistence and/or recurrence was 17.6 (95% CI: 12.3–23.5) in multiple and 14.3 (95% CI: 10.1–19.2) in single HR‐HPV infections detected shortly before or at surgery. The pooled rate of multiple HR‐HPV infections was 25% (95% CI: 20.4–30). The odds ratio of histologically confirmed HSIL persistence and/or recurrence was significantly higher (OR: 1.38, 95% CI:1.08–1.75, p = 0.01, heterogeneity = 39%) among multiple than single HR‐HPV infections. Increased risk of HSIL persistence/recurrence was more marked among studies with multiple HR‐HPVs prevalence ≥25% (12 studies, N = 3476) (OR: 1.47, 95% CI: 1.18–1.84, heterogeneity = 0%) and in those evaluating true histologically confirmed recurrence after at least 6 months of negative follow‐up (9 studies, N = 5073) (OR: 1.67, 95% CI: 1.17–2.37, heterogeneity = 37%). Multiple HR‐HPVs infection detected during follow‐up visits had no effect on the risk of recurrence although the number of included studies was small (4 studies, N = 1248) (OR: 0.98, 95% CI: 0.68–1.39, heterogeneity = 0%). The risk of bias was rated as high in 10 and low‐moderate in 12 studies, respectively. In subgroup analysis, the risk of bias of the included studies (low/moderate vs. high), had a small, although not significant effect on the odds ratios of persistence/recurrence of HSIL (OR: 1.57, 95% CI: 1.23–2 for low‐moderate risk of bias and OR: 1.06, 95% CI: 0.65–1.75 for high risk of bias; p‐value for subgroup differences = 0.17). Conclusions: Multiple HR‐HPVs infections at the time of standard treatment of HSIL entail a small but significant increased risk of persistence/recurrence of HSIL and should be taken into account in the follow‐up plan. [ABSTRACT FROM AUTHOR]

Introduction Long-term exposure to high-risk human papillomavirus (Hr-HPV) is a well-known necessary condition for development of cervical cancer. The aim of this study is to screen for Hr-HPV using vaginal self-sampling, which is a more efective approach to improve women’s adherence and increase screening rates. Methods This pilot study included a total of 100 Women living with HIV (WLWHIV), recruited from the Center for Listening, Care, Animation, and Counseling of People Living with HIV in Bamako. Hr-HPV genotyping was performed on Self-collected samples using the Cepheid GeneXpert instrument. Results The median age of WLWHIV was 44 (interquartile range [IQR], 37–50) years. Approximately 92% of the study participants preferred self-sampling at the clinic, and 90% opted to receive result notifcations via mobile phone contact. The overall prevalence of Hr-HPV among study participants was 42.6%, and the most frequent Hr-HPV sub-types observed were HPV18/45 (19.1%), HPV31/35/33/52/58 (13.8%), and HPV39/68/56/66 (12.8%), followed by HPV16 (5.3%), and HPV51/59 (5.3%). WLWHIV under 35 years of age had a higher frequency of Hr-HPV compared to their older counterparts, with rates of 30% versus 11.1% (p=0.03). The duration of antiretroviral treatment showed an inverse association with Hr-HPV negativity, with patients on treatment for 15 (IQR, 10–18) years versus 12 (IQR=7–14) years for Hr-HPV positive patients (95% CI [1.2–5.8], t=3.04, p=0.003). WLWHIV with baseline CD4 T-Cell counts below 200 exhibited a higher frequency of Hr-HPV compared to those with baseline CD4 T-Cell counts above 200 (17.9% versus 1.9%, p=0.009). However, other demographics and clinical factors, such as marital status, age of sexual debut, parity, education, history of abortion, history of preeclampsia, and cesarean delivery, did not infuence the distribution of Hr-HPV genotypes. Conclusion Our fndings indicate that WLWHIV under the age of 35 years old exhibited the highest prevalence of Hr-HPV infection, with HPV18/45 being the most prevalent subtype. Additionally, WLWHIV with baseline CD4 T-Cell counts below 200 showed the highest infection rates. [ABSTRACT FROM AUTHOR]

Background: The current manuscript's aim was to determine the human papillomavirus (HPV) genotype-specific prevalence and distribution among individuals, males, and females, of different ages in the region of Apulia, Italy, highlighting the possible variables involved in the carcinogenicity mechanism. In addition, we proposed two hypothetical models of HPV's molecular dynamics, intending to clarify the impact of prevention and therapeutic strategies, explicitly modeled by recent survey data. Methods: We presented clinical data from 9647 participants tested for either high-risk (HR) or low-risk (LR) HPV at the affiliated Bari Policlinic University Hospital of Bari from 2011 to 2022. HPV DNA detection was performed using nested-polymerase chain reaction (PCR) and multiplex real-time PCR assay. Statistical analysis showed significant associations for all genders and ages and both HR- and LR-HPV types. A major number of significant pairwise associations were detected for the higher-risk types and females and lower-risk types and males. Results: The overall prevalence of HPV was 50.5% (n-4.869) vs. 49.5% (n-4.778) of the study population, of which 74.4% (n-3621) were found to be HPV high-risk (HR-HPV) genotypes and 57.7% (n-2.807) low-risk HPV (LR-HPV) genotypes, of which males were 58% and females 49%; the three most prevalent HR-HPV genotypes were HPV 53 (n707-15%), 16 (n704-14%), and 31 (n589-12%), and for LR-HPV, they were 42 (19%), 6 (16%), and 54 (13%); 56% of patients screened for HPV were ≤ 30 years old, 53% were between 31 and 40 years old, 46% were 41–50 and 51–60 years old, and finally, 44% of subjects were >60 years old. Conclusions: Our study provided comprehensive epidemiological data on HPV prevalence and genotype distribution among 9647 participants, which could serve as a significant reference for clinical practice, and it implied the necessity for more effective screening methods for HPV carcinogenesis covering the use of more specific molecular investigations. Although this is a predominantly descriptive and epidemiological study, the data obtained offer not only a fairly unique trend compared to other studies of different realities and latitudes but also lead us to focus on the HPV infection within two groups of young people and adults and hypothesize the possible involvement of dysbiosis, stem cells, and the retrotransposition mechanism. [ABSTRACT FROM AUTHOR]

Persistent infection with high-risk human papillomavirus (HR-HPV) is the primary and initiating factor for cervical cancer. With over 200 identified HPV types, including 14 high-risk types that integrate into the host cervical epithelial cell DNA, early determination of HPV infection type is crucial for effective risk stratification and management. Presently, on-site immediate testing during the HPV screening stage, known as Point of Care Testing (POCT), remains immature, severely limiting the scope and scenarios of HPV screening. This study, guided by the genomic sequence patterns of HPV, established a multiplex recombinase polymerase amplification (RPA) technology based on the concept of "universal primers." This approach achieved the multiple amplification of RPA, coupled with the CRISPR/Cas12a system serving as a medium for signal amplification and conversion. The study successfully constructed a POCT combined detection system, denoted as H-MRC12a (HPV—Multiple RPA—CRISPR/Cas12a), and applied it to high-risk HPV typing detection. The system accomplished the typing detection of six high-risk HPV types (16, 18, 31, 33, 35, and 45) can be completed within 40 min, and the entire process, from sample loading to result interpretation, can be accomplished within 45 min, with a detection depth reaching 1 copy/μL for each high-risk type. Validation of the H-MRC12a detection system's reproducibility and specificity was further conducted through QPCR on 34 clinical samples. Additionally, this study explored and optimized the multiplex RPA amplification system and CRISPR system at the molecular mechanism level. Furthermore, the primer design strategy developed in this study offers the potential to enhance the throughput of H-MRC12a detection while ensuring sensitivity, providing a novel research avenue for high-throughput detection in Point-of-Care molecular pathogen studies. [ABSTRACT FROM AUTHOR]

Context: CytoPath®Easy kit (DiaPath S.p.A.) offers a major advantage compared to other commercially available kits available for the screening of cervical cancer, as it does not require additional equipment for sample processing. Using this methodology, collected epithelial cells are immersed in a preservative liquid before setting as a thin layer on a slide via gravity sedimentation. Aims: To evaluate the suitability of the CytoPath®Easy kit for the processing of cervical samples, detection of pre-neoplastic lesions, and nucleic preservation and extraction for HR-HPV diagnosis. Materials and Methods: A total of 242 self-sampled cervical specimens were utilized, with 192 collected in CytoPath®Easy vials and 50 collected and processed using the ThinPrep™ for comparative analysis. The samples underwent processing, Papanicolaou staining, and microscopic evaluation for morphological parameters. The extracted nucleic acids were assessed for purity and integrity, and the detection of high-risk human papillomavirus (HR-HPV) was carried out using the Alinitym HR HPV system kit (Abbott Laboratórios Lda). Results: Both methods demonstrated effective performance, enabling the morphological assessment of the cervical epithelium. Statistical analysis indicated that ThinPrepTM yielded significantly better results in terms of cellularity. Conversely, CytoPath®Easy exhibited superior performance in terms of the quantity of extracted DNA and its degree of purification. Concerning the time consumed during processing, both methods were comparable, with the CytoPath®Easy methodology standing out for its cost-effectiveness, as it does not necessitate additional instruments and consumables. Conclusions: The novel CytoPath®Easy methodology proves effective in preserving both nucleic acids and cell morphology characteristics, two crucial features for cervical cancer screening. [ABSTRACT FROM AUTHOR]

Background: Human papillomavirus (HPV) is currently the most common pathogen responsible for cervical cancer (CC), a major cause of cancer-related deaths in women. This study aimed to estimate the current HPV prevalence in Bahrain and to determine the association of high-risk HPV (HR-HPV) genotypes with cytological findings, age, and clinical history of the patients. Methods and Results: Our study used a retrospective approach. Convenience sampling was used to gather 100 cases of HPV-positive women with abnormal and normal Pap smear findings from January 2017 to April 2023 in the Cytology Department at King Hamad University Hospital. Out of 100 HR-HPV positive cases, non-16/18/45 HR-HPV was found in 62%, and 73% had abnormal Pap smear findings. Among Pap smear findings, ASC-US/ASC-H (P=0.038) and LSIL/HSIL(P=0.017) were significantly associated with HR-HPV genotypes. ASC-US was found to be more frequently associated with HPV16+non-16/18/45 HR-HRV and LSIL with HPV18/45+non-16/18/45 HR-HRV. Most HR-HPV cases (59%) were aged ≤40 years, 25% - from 41 to 50 years old, while only 16% were >50. The age group ≤40 had the highest peak with non-16/18/45 HR-HPV genotype (35%) and HPV16 (19%). The predominant genotypes for age groups 41-50 and >50 were non-16/18/45 HR-HPV types (19% and 8%, respectively). Conclusion: In Bahrain, non-16/18/45 HR-HPV infection is becoming more prevalent, with ASC-US being the most common abnormal Pap finding and the highest HPV infection in women aged 40 years or younger. Based on our findings, we recommend effective screening and vaccine programs for women aged 40 years and younger, as early detection can lower infection rates and improve recovery.

Abstract Persistent infection with high-risk human papillomavirus (HR-HPV) is the primary and initiating factor for cervical cancer. With over 200 identified HPV types, including 14 high-risk types that integrate into the host cervical epithelial cell DNA, early determination of HPV infection type is crucial for effective risk stratification and management. Presently, on-site immediate testing during the HPV screening stage, known as Point of Care Testing (POCT), remains immature, severely limiting the scope and scenarios of HPV screening. This study, guided by the genomic sequence patterns of HPV, established a multiplex recombinase polymerase amplification (RPA) technology based on the concept of “universal primers.” This approach achieved the multiple amplification of RPA, coupled with the CRISPR/Cas12a system serving as a medium for signal amplification and conversion. The study successfully constructed a POCT combined detection system, denoted as H-MRC12a (HPV—Multiple RPA—CRISPR/Cas12a), and applied it to high-risk HPV typing detection. The system accomplished the typing detection of six high-risk HPV types (16, 18, 31, 33, 35, and 45) can be completed within 40 min, and the entire process, from sample loading to result interpretation, can be accomplished within 45 min, with a detection depth reaching 1 copy/μL for each high-risk type. Validation of the H-MRC12a detection system’s reproducibility and specificity was further conducted through QPCR on 34 clinical samples. Additionally, this study explored and optimized the multiplex RPA amplification system and CRISPR system at the molecular mechanism level. Furthermore, the primer design strategy developed in this study offers the potential to enhance the throughput of H-MRC12a detection while ensuring sensitivity, providing a novel research avenue for high-throughput detection in Point-of-Care molecular pathogen studies.

Background/Aim: It has been well established that human papilloma virus (HPV) is the major cause of cervical pre-cancerous lesions and cervical cancer. Extended HPV genotyping has pointed out that co-infections with multiple high-risk (HR)-HPV genotypes not only is possible and quite frequent, but also has different prognoses. The purpose of this study was to evaluate the prevalence of co-infections in women tested for HR-HPV in the national cervical cancer screening program of Lazio (Italy). Patients and Methods: From June 1st to November 30th 2022, we analyzed 30,445 samples of women aged between 30 and 64 years, using the Anyplex TM II HPV HR Detection test by Seegene (Arrow), which identifies 14 HPV genotypes: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68. The data were analyzed using the SG STATS platform. Results: In total, 4,244 (13.94%) were positive: 3,290 (77.52%) showed a single genotype infection and 954 (22.48%) an infection with 2 to 5 different genotypes. In 721 (75.60%) cases, two different genotypes were detected, in 191 (20.00%) there were three genotypes, in 41 (4.30%) cases there were four genotypes and in only one case (0.10%) five different genotypes were detected. HPV 16 (262 cases of co-infections) was associated in 27 cases with HPV 31 genotype, in 25 cases with HPV 68 and in 18 cases with HPV 58. Conclusion: HPV 16 was the most frequent genotype detected in co-infections. Immunity status, vaccination, lifestyle, and other possible risk factors, such as the combination of the HR-HPV genotype multiple infections, may influence the development and progression of the disease. [ABSTRACT FROM AUTHOR]

Abstract Background HPV screening tests may improve cervical cancer risk stratification and better guide decisions about follow-up with colposcopy/biopsy. This study aimed to estimate the risk of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) among women with oncogenic HPV types and evaluate the performance of colposcopy in the diagnosis of histologic CIN2 + at Putuo Hospital, Shanghai, China. Methods This cross-sectional survey was conducted from February 2020 to December 2022 among women who were referred to colposcopy. Women with high-risk (HR) HPV-positive, cytology testing and colposcopy-directed biopsy were included. Results Univariate and multivariate analysis indicated that high-grade colposcopic impression ((OR, 17.61%, 95%CI: 11.54–26.85%) was associated with the highest risk for detecting CIN2+, followed by HSIL + cytology (OR, 6.90%, 95%CI: 3.56–13.37%) and HPV16/18 positive (OR, 2.91%, 95%CI: 2.12–3.99%). Overall, CIN2 + was detected in 14.6% of 2007 women. HPV16/18 had higher CIN2 + risks than other HR-HPV genotypes (30.1% vs. 10.2%, P 0.05). The diagnostic performance of colposcopy in diagnosis of CIN2 + by senior and junior colposcopists was comparable. Conclusions The results indicated that referral to colposcopy is recommended in managing women with HR-HPV positive, and colposcopic impressions provide key clues for identification CIN2+.

Objective Our objective was to investigate the therapeutic mechanism of quercetin in the management of cervical HR-HPV through the integration of network pharmacology and molecular docking techniques.

BackgroundPersistent infection with high-risk human papillomavirus (HR-HPV) can lead to cervical intraepithelial neoplasia and cancer. At present, there is no medication that specifically targets HR-HPV infection.ObjectiveThis study aimed to evaluate the effectiveness of different interventions in promoting HR-HPV regression using a MeSH meta-analysis method.MethodsA search for randomized controlled trials (RCTs) reporting different interventions for the treatment of HR-HPV infection included PubMed, Web of Science, Embase and Cochrane Library from the inception of the databases to March 8, 2023. Two researchers independently screened the articles, extracted data, and evaluated the quality. The literature that met the inclusion criteria was selected, the quality and risk of bias of the included studies were assessed according to the Cochrane 5.1 manual, and NMA was performed using Stata 16.0. The area under the cumulative ranking probability graph (SUCRA) represented the probability that each treatment would be the best intervention.ResultsNine studies involving 961 patients and 7 treatment options were included in the analysis. The results of the network meta-analysis indicated the following rank order in terms of promoting HR-HPV conversion: Anti-HPV biological dressing > vaginal gel > imiquimod > REBACIN® > interferon > probiotics > observation/placebo > Polyphenon E.ConclusionAnti-HPV biological dressing treatment was found to be significantly effective in promoting HR-HPV conversion. However, further validation of the findings is necessary due to the limited number and quality of studies included in the analysis.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42023413917.

Background: The aim of the study is to analyze the morphological characteristics of p16INK4a/Ki-67 dual stained cells (DS) in cytology, to expand understanding of potential diagnostic value of integration of biomarkers in cytology and contribute to the existing knowledge on their utility in cervical cancer screening. Materials and Methods: In our study included a total 162 woman, who had previous abnormal Pap screening results and were enrolled in an opportunistic screening program. For these participants 162 pap /p16INK4a/Ki-67 co- tests results and 29 histopathology results were available. Results: In our study, sensitivity, specificity, PPV, NPV and accuracy of p16INK4a/Ki-67 DS of cervical smear, with abnormal morphology of stained cells to detect histologic high-grade cervical intraepithelial neoplasia (CIN2+) were 91%, 94%, 93%, 94% and 93%, respectively(p<0.01). There occur 1 error. Conclusions: Our study reveals that p16INK4a/Ki-67 DS cytology is superior in detecting CIN2+ to compare pap test, but morphologic categorization of p16INK4a/Ki-67 DS cytology is not superior over morphologic non-categorization of DS cytology in detecting high grade precancerous lesion during cervical cancer screening. [ABSTRACT FROM AUTHOR]

Nicotine is a known toxin, but its relationship with cervicovaginal high-risk human papillomavirus (HR-HPV) infection is uncertain. This study aimed to investigate whether tobacco exposure is associated with elevated cervicovaginal HR-HPV infection in US women, and if the strength of this association varies with the degree of exposure. Cross-sectional data from the 2011–2016 National Health and Nutrition Examination Survey (NHANES), which included a nationally representative sample of US women, were used for the study. Out of 12436 women aged 18–59 who participated in the interview, 3833 were ultimately enrolled in this study. Weighted logistic regression was used to estimate the link between tobacco exposure and cervicovaginal HR-HPV infection. The mean age of participants was 38.6 (SD 12.1) years, and non-Hispanic White individuals accounted for 37.3% of the sample. Those with any tobacco exposure tended to be younger (mean age 37.7 [SD 12.4] years vs 40.3 [11.2] years), non-Hispanic Black (27.8% vs. 15.1%), lower educated (41.8% vs. 29.4%), and have lower family income (39.9% vs. 23.5%). After adjustment, the odds of having HR-HPV infection were 1.32 (95% CI, 1.09–1.59) for those exposed to tobacco, remaining significant in multiple sensitivity analyses and across subgroups. This study, based on a nationally representative sample from the United States, suggests that tobacco exposure is a risk factor for elevated HR-HPV infection in women, highlighting the need for further research into reducing this modifiable risk factor. [ABSTRACT FROM AUTHOR]

Abstract Background Human papilloma virus (HPV) is a sexually transmitted infection causing more than 80% of cervical cancers. WHO recommends using of sensitive screening methods like HPV-testing to timely prevent future morbidity and mortality from cervical cancer. Pilot studies have shown that HPV-testing is feasible and can be scaled in developing country like Tanzania. However, there is limited information on women understanding, reactions and psychological challenges following diagnosis of high risk HPV (HR-HPV). This study explored the knowledge of women on HPV and their experience after HPV positive results in Kilimanjaro, Tanzania. Methods The study was part of a larger study that assessed incidence and persistence of HR-HPV among women aged 18 years and above in Kilimanjaro. This was a cross sectional study conducted in Moshi municipal council among women who had HR-HPV positive results at enrollment. In-depth interviews were conducted with 13 randomly selected women who were attending for follow-up after enrollment. Interviews were conducted at the health facility and Atlas.ti.8 was used to analyze the data using thematic framework analysis. Results Women had knowledge on HPV infection but they had different reactions following receiving positive HPV results. Reaction toward the positive HPV results had two extremes; some women had psychological effect (hopeless, death sentence, having cancer, being shocked, failure to disclose and psychosexual effects) while others women explained positive results is good as they are identified earlier, will be followed up and it has made them plan to continue with cervical cancer screening in future. Conclusion Women had knowledge on HPV, but positive results lead to negative and positive experiences by women. Clinicians and programs need to develop interventions and good strategies to minimize the psychological and social burden of testing positive for HPV.

Abstract Background Human papillomavirus (HPV) genotypes differ by geographic location. With the advent of HPV vaccination and HPV-based cervical screening tests in Ethiopia, a nationwide dataset on the genotype distribution of HPV among women has paramount importance in the fight against cervical cancer. However, there is limited data in this regard in the northwest part of the country. Therefore, this study aimed to identify the genotype distribution of high-risk HPVs among women presenting with cervical abnormalities. Methods A health facility-based cross-sectional study was conducted at Felege Hiwot Comprehensive Specialized Hospital (FHCSH), Bahir Dar–Ethiopia. Women aged ≥ 30 years who visited the hospital gynecology unit from 01 March 2019 to 30 October 2021 were included. Following general and pelvic examinations, a senior gynecologist collected cervical punch biopsies for histopathological examinations and cervical swabs for HR-HPV detection using the Abbott Alinity m system (Abbott Molecular, Des Plaines, IL, USA). Extended genotyping was carried out with the INNO-LiPA HPV Genotyping Extra II assay (INNO-LiPA; Fujirebio Europe, Ghent, Belgium) as per the manufacturer protocols at the Institute of Virology, Leipzig University Hospital, Germany. Results We included 355 women with a mean age of 46.4 ± 11.4 years. The majority of the participants, 277 (79.4%) were sexually active before the age of 18 years and 180 (51.6%) had multiple sexual partners. Forty-eight (13.5%) of the participants were HIV positive. The proportion of HR-HPV was 53.0% (n = 188; 95%CI: 47.8–58.1%). From these samples, 13 different HR-HPV types with a total of 258 sequences were identified. The detection of HR-HPV increased significantly with an increase in the age of the participants. The predominant identified HR-HPV was HPV16, 50.4% followed by HPV31 (9.7%), HPV33 (8.5%), HPV39, and HPV68 each (5.8%) and HPV18 (4.7%). Of the total HR-HPV-positive women, 23.9% (45/188) were infected with multiple HR-HPV types. All HPV16, HPV18, HPV35, and HPV45 genotypes (as a single or in coinfections) were found to be associated with either high-grade lesions or cervical cancer. Conclusions HR-HPV infection was reportedly higher among women in the present study area. Based on our findings, we strongly recommend the nonavalent HPV vaccine for immunization and any HPV-based screening method to take into consideration the predominant genotypes circulating in the country. The role of multiple HPV infections in high-grade cervical lesions entails further study in Ethiopia.

Background: HPV screening tests may improve cervical cancer risk stratification and better guide decisions about follow-up with colposcopy/biopsy. This study aimed to estimate the risk of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) among women with oncogenic HPV types and evaluate the performance of colposcopy in the diagnosis of histologic CIN2 + at Putuo Hospital, Shanghai, China. Methods: This cross-sectional survey was conducted from February 2020 to December 2022 among women who were referred to colposcopy. Women with high-risk (HR) HPV-positive, cytology testing and colposcopy-directed biopsy were included. Results: Univariate and multivariate analysis indicated that high-grade colposcopic impression ((OR, 17.61%, 95%CI: 11.54–26.85%) was associated with the highest risk for detecting CIN2+, followed by HSIL + cytology (OR, 6.90%, 95%CI: 3.56–13.37%) and HPV16/18 positive (OR, 2.91%, 95%CI: 2.12–3.99%). Overall, CIN2 + was detected in 14.6% of 2007 women. HPV16/18 had higher CIN2 + risks than other HR-HPV genotypes (30.1% vs. 10.2%, P<0.001). Among women with low-grade cytology, 24.1% had CIN2+, and the risks for HPV16/18 (58.2%) were higher than for other HR-HPV(16.8%). For those with high-grade cytology, there was no significant difference between HPV groups (75.0% vs. 72.9%, P > 0.05). The diagnostic performance of colposcopy in diagnosis of CIN2 + by senior and junior colposcopists was comparable. Conclusions: The results indicated that referral to colposcopy is recommended in managing women with HR-HPV positive, and colposcopic impressions provide key clues for identification CIN2+. [ABSTRACT FROM AUTHOR]

Background: Sub-Saharan Africa (SSA) carries the highest burden of high-risk human papillomavirus (HR-HPV) in the world, driven by, and together with, HIV infection. This systematic review aimed to identify HR-HPV genotypes and their associated factors among women in SSA. Methods: A systematic review and meta-analysis of studies conducted in SSA on HR-HPV was conducted. Standard electronic databases were searched. R software version 3.6.0 was used for meta-analysis, with p < 0.05 considered statistically significant. Results: We included 28 articles with a total of 22,652 participants. The overall pooled prevalence of HR-HPV genotypes was 55.13%, albeit high heterogeneity between studies. The overall pooled prevalence of HR-HPV genotypes in HIV-positive individuals was 75.51%, compared to 52.97% in HIV-negatives (OR = 4.68 (0.71–30.76)). HPV 16 (18%), 35 (10.12%), 52 (9.98%), 18 (9.7%) and 45 (6.82%) genotypes were the most prevalent. Twelve studies identified the most frequently reported risk factors associated with HR-HPV, with HIV infection (66.66%), multiple sexual partners (41.66%) and young age (41.66%) being the most reported risk factors. Conclusions: The combined prevalence of HR-HPV genotypes among women in general and HIV-infected women in particular remains high in SSA. The presence of several genotypes not covered by the vaccine is remarkable and suggests the need for revision of current vaccination policies to prevent HR-HPV infections. [ABSTRACT FROM AUTHOR]

Cervical lesions, induced by high-risk oncogenic human papillomavirus (HR-HPV), in the context of HIV remains a global health challenge. We determined the effect of HR-HPV on the development of cervical lesions in women with and without HIV infection. A cross-sectional analytical study was conducted among 257 women living in Cameroon. HIV serology, HR-HPV genotyping and cervico-vaginal smear (CVS) were performed for all participants; among those declared HIV positive, plasma HIV viral load and CD4 count were measured. Statistical analyses were performed using Graph Pad version 6.0; P0.05 was considered statistically significant. The mean age of the participants in our study was 37±6.5 years. According to HIV serology, 184 (71.59%) were HIV‑positive vs. 73 (28.40%) HIV‑negative. Among the HIV‑positive women, the median CD4 count was 438 [IQR: 317‑597] cells/mm3 and the median viremia was 40 [IQR:40‑2318] copies/ml. After successful genotyping, the prevalence of HR‑HPV was 36.32% (73/201), with a significantly higher proportion in HIV‑infected individuals (41.98% (55/131) vs. 25.71% (18/70); P=0.02; OR=2.1). The overall rate of cervical lesions was 23.34% (60/257), with a non‑significantly higher proportion in HIV‑infected participants (25.00%(46/184) vs. 19.17% (14/73); P=0.31). Relevantly, the presence of HR‑HPV was significantly associated with cervical lesions (P0.0001; OR=5.07), with a higher odds of cervical lesion in HIV‑positive individuals (P0.0001 and OR=5.67) compared to HIV‑negative individuals (P=0.03 and OR=3.83). Although oncogenic HPV appears to be an independent factor in the development of cervical lesions, this study reveals higher odds of cervical lesions among HIV/HPV co-infection than in HPV infection alone.

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Introduction: Xingu Indigenous Park (XIP) currently protects 16 ethnic Indigenous groups and is located in the central area of Brazil. XIP is the first and the largest Indigenous land to be recognized in the country. Community access is limited and restricted for the non-Indigenous population, and the Indigenous women are constantly dealing with shortages of medical care. High-risk human papillomavirus (HR-HPV) is the most common cause of cervical cancer and is detected in 99% of cervical precancers. HPV infections may be associated with bacterial agents such as Chlamydia trachomatis and Neisseria gonorrhoeae, which are also important causative agents of sexually transmitted infections and are responsible for the most frequent bacterial infections in the world. The present study evaluated the frequency and potential impact of Chlamydia trachomatis, Neisseria gonorrhoeae, and HR-HPV in the Indigenous women of XIP. Methods: In this cross-sectional study, 992 cervical--vaginal samples were collected from Indigenous women, using a Cervex- Brush, and were immediately placed in a SurePath medium. All samples were submitted to the cobas® 4800 detection system for the identification of 14 different types of HR-HPV, and the multiplex Abbott RealTime CT/NG assay for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae. Results: HR-HPV was detected in 18.2% of women; 6% were positive for HPV16, 5% for HPV18, and 81% for other types of HRHPV. Co-infections of HPV16 and other types was observed in 5% of women, and 3% had co-infections of HPV18 and other types. Moreover, 1.8% of women were positive for Chlamydia trachomatis, while Neisseria gonorrhoeae was not detected. In women with HR-HPV, 33% had Chlamydia trachomatis infections, 28% were positive for HR-HPV other than HPV16 or HPV18, and 5% had co-infections of HPV16 and the other types of HPV. Younger women were found to be more susceptible to HPV infections. Conclusion: The findings indicate a high frequency of HR-HPV and a considerable frequency of Chlamydia trachomatis in the Indigenous women of XIP. The detection of Chlamydia trachomatis, Neisseria gonorrhoeae, and/or HR-HPV does not present evidence of a potential interrelationship for a combined pathogenic action in these women. [ABSTRACT FROM AUTHOR]

Genital human papillomavirus (HPV) infection is widespread among sexually active individuals. Several factors may contribute to increased risk of infection in pregnant women. The objective of this study was to determine the high-risk (HR-HPV) and low-risk (LR-HPV) oncogenic HPV genotypes among pregnant women in Ouagadougou.

Lijuan Zhuang &ast;, Xiulan Weng &ast;, Lihua Wang, Xiaoyan Xie, Liying Zhong, Dabin Liu, Yingling Xiu Department of Obstetrics and Gynecology, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yingling Xiu; Dabin Liu, Department of Obstetrics and Gynecology, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, 18 Daoshan Road, Fuzhou, People’s Republic of China, Tel +86-13860610354 ; +86-13489997701, Fax +86-591-87551247, Email xiuyingling@fjmu.edu.cn; xiuyingling1985@163.com; 15968250@qq.comPurpose: A high-risk human papillomavirus E6/E7 mRNA (HR-HPV mRNA) assay is widely used in cervical cancer screening in China. However, it is still unclear whether stand-alone HR-HPV mRNA testing is sufficient for primary screening. The purpose of this study was to investigate the feasibility of a stand-alone HR-HPV mRNA assay for primary screening of cervical cancer.Methods: Women aged 21 and older were recruited in Fujian Province, China, from January 2020 to January 2022. Cervical exfoliated cells were collected for cervical cytology and HR-HPV mRNA assays, and women with positive results on either assay were referred for colposcopy. The screening effectiveness of the assay was calculated based on the cervical histology. When comparing the efficacy of the different screening strategies, only women aged 25 and older were included.Results: A total of 9927 women were recruited. This study identified 217 cases of high-grade squamous intraepithelial disease or worse (HSIL+). The overall age-specific HR-HPV infection rate showed a U-shaped distribution. The sensitivity of the HR-HPV mRNA assay to identify CIN2+ and CIN3+ was 97.2% and 97.9%, respectively, which was significantly higher than that of cytology (82.9% and 88.6%, P< 0.001 and 0.002). The sensitivity of the HR-HPV mRNA primary screening strategy to identify CIN2+ and CIN3+ was 92.2% and 94.3%, respectively, which was similar to the co-testing strategy (P=0.336 and 0.394) and higher than the cytology primary screening (P=0.002 and 0.048). In addition, the HR-HPV primary screening strategy had a lower referral rate for colposcopy than cytology primary screening (5.4% vs 6.6%, P< 0.001), and the screening cost was lower than co-testing (&dollar;29,594.3 per 1000 screened women vs &dollar;55,140 per 1000 screened women, P< 0.001).Conclusion: In conclusion, the detection of CIN2+/CIN3+ by HR-HPV mRNA is both specific and sensitive. It may be suitable for primary screening of cervical cancer in China.Keywords: cervical cancer, HR-HPV, E6/E7 mRNA, primary screening, cervical intraepithelial neoplasia

PurposeThis study aims to address the existing data gap regarding the status of high-risk human papillomavirus (HR-HPV) infection and the distribution of HR-HPV subtypes among women in rural areas of Nyingchi City, Tibet. The research objectives include providing insights for HPV vaccine development.MethodsThe research collected data from two rounds of cancer screening conducted among rural women in Nyingchi City, Tibet, from 2019 to 2022. HR-HPV subtype gene detection was performed using the PCR fluorescence method on the collected samples. And then analyzed the HR-HPV infection rate among rural women in Nyingchi City, Tibet, as well as the infection rate of different HR-HPV subtypes and their distribution across different age groups. A comparison was made between the infection rates of women in rural areas outside the Qinghai-Tibet Plateau and those in Nyingchi City.ResultsA total of 15,687 cases included. The overall HR-HPV infection rate among women in rural areas of Nyingchi City, Tibet, was 13.00% (2040/15,687), which was significantly higher than the rate among women in rural areas outside the Qinghai-Tibet Plateau (7.82% (9,249/118,237); χ2 = 635.7, p

Cervical cancer is the second most malignant tumor among women of childbearing age, almost all cervical cancers are associated with high-risk (HR) human papillomavirus (HPV) persistent infection. HPV persistent infection and cell immortalization does not always cause cancer, but they increase risk and can lead to tumor formation and carcinogenesis in cooperation with other tumorigenic factors, and HR-HPV E6 oncoprotein is the mainly tumorigenic factors.E6 binds to the highly conserved sequence “LXXLL” of E6AP to form a heterodimer, which recruits and induces the degradation of tumor suppressor protein p53, trigger the immortalized transformation of infected cells, and induce its carcinogenicity. Therefore, the small molecule compounds, who can compete the conservative and stable binding pocket of E6-E6AP, may inhibited the carcinogenicity risk of HR-HPV E6, and HPV-16 is one of the most important HR-HPV.In this study, DOCK6, AutoDock Vina, Visual screen and GROMACS V4.5.7 were used to screen the candidate compounds from Specs library, and based on the pharmacokinetic properties and toxicity prediction by ADMSlab and ProtoX-II analytical tools, 20 E6-E6AP binding inhibition small molecule compounds were selected out. They were verified by molecular interactions, cell proliferation inhibition, apoptosis induction and p53/p21 protein content/expression on SiHa (HPV-16 infected line). Ultimately, compound 4 among them with good tumor suppressive potential was picked out, has the potential of medicine to HR-HPV related diseases.

Introduction: Xingu Indigenous Park (XIP) currently protects 16 ethnic Indigenous groups and is located in the central area of Brazil. XIP is the first and the largest Indigenous land to be recognized in the country. Community access is limited and restricted for the non-Indigenous population, and the Indigenous women are constantly dealing with shortages of medical care. High-risk human papillomavirus (HR-HPV) is the most common cause of cervical cancer and is detected in 99% of cervical precancers. HPV infections may be associated with bacterial agents such as Chlamydia trachomatis and Neisseria gonorrhoeae, which are also important causative agents of sexually transmitted infections and are responsible for the most frequent bacterial infections in the world. The present study evaluated the frequency and potential impact of Chlamydia trachomatis, Neisseria gonorrhoeae, and HR-HPV in the Indigenous women of XIP. Methods: In this cross-sectional study, 992 cervical-vaginal samples were collected from Indigenous women, using a Cervex-Brush, and were immediately placed in a SurePath medium. All samples were submitted to the cobas® 4800 detection system for the identification of 14 different types of HR-HPV, and the multiplex Abbott RealTime CT/NG assay for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae. Results: HR-HPV was detected in 18.2% of women; 6% were positive for HPV16, 5% for HPV18, and 81% for other types of HR-HPV. Co-infections of HPV16 and other types was observed in 5% of women, and 3% had co-infections of HPV18 and other types. Moreover, 1.8% of women were positive for Chlamydia trachomatis, while Neisseria gonorrhoeae was not detected. In women with HR-HPV, 33% had Chlamydia trachomatis infections, 28% were positive for HR-HPV other than HPV16 or HPV18, and 5% had co-infections of HPV16 and the other types of HPV. Younger women were found to be more susceptible to HPV infections. Conclusion: The findings indicate a high frequency of HR-HPV and a considerable frequency of Chlamydia trachomatis in the Indigenous women of XIP. The detection of Chlamydia trachomatis, Neisseria gonorrhoeae, and/or HR-HPV does not present evidence of a potential interrelationship for a combined pathogenic action in these women.

Aim: Human papillomavirus (HPV) is the most common cause of high-grade lesions and carcinogenesis such as cervical intraepithelial neoplasia (CIN) and cervical cancer (CC). The prevalence and genotype distribution of HPV infection varies greatly in different geographical areas. Patients & methods: This study enrolled 92,932 patients from January 2017 to December 2021 and analyzed the prevalence and distribution of HPV genotypes. Results: 18038 (19.41%) specimens were HPV-positive. No significant difference in infection rates between men and women (19.05 vs 19.41%). The most prevalent HPV subtypes are HPV52, HPV58, HPV16, HPV53, HPV51 and HPV81. Single infection of HPV has dominated in HPV-positive patients. Conclusion: Our results show that the prevalence and distribution of HPV subtypes have obvious region-specific and age-specific characteristics. [ABSTRACT FROM AUTHOR]

Fang Zhao,1 Deyong Ma,2 Tingting Wang,3 Yan Zhang,2 Ying Dong,4 Jian Zhao2 1Department of Obstetrics and Gynecology, Beijing Jishuitan Hospital, Beijing, 100035, People’s Republic of China; 2Department of Obstetrics and Gynecology, Peking University First Hospital of Obstetrics and Gynecology, Beijing, 100034, People’s Republic of China; 3Peking University Department of Medicine, Beijing, 100191, People’s Republic of China; 4Department of Pathology, Peking University First Hospital of Obstetrics and Gynecology, Beijing, 100034, People’s Republic of ChinaCorrespondence: Jian Zhao, Email JianZhao112@outlook.comObjective: The aim of this study was to clinically evaluate the application of liquid-based cytology P16, cytologic evaluation, and high-risk human papillomavirus (HR-HPV) testing in cervical cancer screening.Methods: This study screened 900 women, who attended the outpatient clinic, according to the exclusion criteria of study participants. The study participants’ screening results of liquid-based cytology P16, cytologic evaluation, and HR-HPV testing were analyzed. According to the pathological results of the biopsy, the efficacy of different screening strategies for the identification of high-grade lesions was evaluated.Results: The positive rate of p16 expression increased with the severity of cervical lesions. P16 had the highest sensitivity and negative predictive value in identifying high-grade lesions (98.45% and 99.67%, respectively). Liquid-based Papanicolaou test (LBP), on the other hand, had the lowest sensitivity (85.27%) but the highest specificity (85.88%). HR-HPV’s positive predictive value and accuracy rate were the lowest (32.77% and 70.03%, respectively). The difference was statistically significant (P < 0.05). Dual combinations of certain tests were set up for this study; P16+LBP, HPV+LBP, and P16+HPV had sensitivities of 98.45%, 96.90%, and 99.22%, and specificities of 80.29%, 63.42%, and 64.33%, respectively. The P16 screening rates of histological and liquid-based cytology approaches were 75.74%.Conclusion: Compared with traditional LBP+HPV, the application of a test that solely screen for P16 or the combined screening method that involves the screening of P16 is more effective in identifying high-grade lesions.Keywords: biomarkers, liquid-based cytology, p16, HR-HPV, screening of high-grade cervical lesions

The effect of cervical cancer immunotherapy is limited. Combination therapy will be a new direction for cervical cancer. Thus, it is essential to discover a novel and available predictive biomarker to stratify patients who may benefit from immunotherapy for cervical cancer. In this study, 563 participants were enrolled. Adenylate cyclase 7 (ADCY7) mRNA was detected by real-time quantitative PCR (qPCR) with cervical cytology specimens. The relationship between ADCY7 and cervical intraepithelial neoplasia in grade 2 and higher (CIN2+) was analyzed, and the optimal cut-off values of the relative expression of ADCY7 mRNA to predict CIN2+ were calculated. In addition, the clinical significance of ADCY7 in cervical cancer was determined by the Kaplan–Meier Cox regression based on the TCGA database. The mean ADCY7 mRNA expression increased significantly with cervical lesion development, especially compared with CIN2+ (p < 0.05). Moreover, the expression of ADCY7 increased significantly in high-risk human papillomavirus (HR-HPV) infection but not in HPV-A5/6 species. The area under the receiver operating characteristic curve (AUC) of ADCY7 was 0.897, and an optimal cut-off was 0.435. Furthermore, ADCY7 had the highest OR (OR= 8.589; 95% CI (2.281–22.339)) for detecting CIN 2+, followed by HPV genotyping, TCT, and age (OR = 4.487, OR = 2.071, and OR = 1.345; 95% CI (1.156–10.518), (0.370–8.137), and (0.171–4.694), respectively). Moreover, this study indicated that higher ADCY7 levels could be a suitable predictor for poor prognosis in cervical cancer due to immune cell infiltration. A new auxiliary predictor of CIN2+ in cervical cytology specimens is ADCY7 ≥ 0.435. Furthermore, it may be a promising prognosis predictor and potential immunotherapy target for the combined treatment of cervical cancer and possibly further block HR-HPV persistent infection. [ABSTRACT FROM AUTHOR]

Background: Human papilloma virus (HPV) is a sexually transmitted infection causing more than 80% of cervical cancers. WHO recommends using of sensitive screening methods like HPV-testing to timely prevent future morbidity and mortality from cervical cancer. Pilot studies have shown that HPV-testing is feasible and can be scaled in developing country like Tanzania. However, there is limited information on women understanding, reactions and psychological challenges following diagnosis of high risk HPV (HR-HPV). This study explored the knowledge of women on HPV and their experience after HPV positive results in Kilimanjaro, Tanzania. Methods: The study was part of a larger study that assessed incidence and persistence of HR-HPV among women aged 18 years and above in Kilimanjaro. This was a cross sectional study conducted in Moshi municipal council among women who had HR-HPV positive results at enrollment. In-depth interviews were conducted with 13 randomly selected women who were attending for follow-up after enrollment. Interviews were conducted at the health facility and Atlas.ti.8 was used to analyze the data using thematic framework analysis. Results: Women had knowledge on HPV infection but they had different reactions following receiving positive HPV results. Reaction toward the positive HPV results had two extremes; some women had psychological effect (hopeless, death sentence, having cancer, being shocked, failure to disclose and psychosexual effects) while others women explained positive results is good as they are identified earlier, will be followed up and it has made them plan to continue with cervical cancer screening in future. Conclusion: Women had knowledge on HPV, but positive results lead to negative and positive experiences by women. Clinicians and programs need to develop interventions and good strategies to minimize the psychological and social burden of testing positive for HPV. [ABSTRACT FROM AUTHOR]

Background: Human papillomavirus (HPV) genotypes differ by geographic location. With the advent of HPV vaccination and HPV-based cervical screening tests in Ethiopia, a nationwide dataset on the genotype distribution of HPV among women has paramount importance in the fight against cervical cancer. However, there is limited data in this regard in the northwest part of the country. Therefore, this study aimed to identify the genotype distribution of high-risk HPVs among women presenting with cervical abnormalities. Methods: A health facility-based cross-sectional study was conducted at Felege Hiwot Comprehensive Specialized Hospital (FHCSH), Bahir Dar–Ethiopia. Women aged ≥ 30 years who visited the hospital gynecology unit from 01 March 2019 to 30 October 2021 were included. Following general and pelvic examinations, a senior gynecologist collected cervical punch biopsies for histopathological examinations and cervical swabs for HR-HPV detection using the Abbott Alinity m system (Abbott Molecular, Des Plaines, IL, USA). Extended genotyping was carried out with the INNO-LiPA HPV Genotyping Extra II assay (INNO-LiPA; Fujirebio Europe, Ghent, Belgium) as per the manufacturer protocols at the Institute of Virology, Leipzig University Hospital, Germany. Results: We included 355 women with a mean age of 46.4 ± 11.4 years. The majority of the participants, 277 (79.4%) were sexually active before the age of 18 years and 180 (51.6%) had multiple sexual partners. Forty-eight (13.5%) of the participants were HIV positive. The proportion of HR-HPV was 53.0% (n = 188; 95%CI: 47.8–58.1%). From these samples, 13 different HR-HPV types with a total of 258 sequences were identified. The detection of HR-HPV increased significantly with an increase in the age of the participants. The predominant identified HR-HPV was HPV16, 50.4% followed by HPV31 (9.7%), HPV33 (8.5%), HPV39, and HPV68 each (5.8%) and HPV18 (4.7%). Of the total HR-HPV-positive women, 23.9% (45/188) were infected with multiple HR-HPV types. All HPV16, HPV18, HPV35, and HPV45 genotypes (as a single or in coinfections) were found to be associated with either high-grade lesions or cervical cancer. Conclusions: HR-HPV infection was reportedly higher among women in the present study area. Based on our findings, we strongly recommend the nonavalent HPV vaccine for immunization and any HPV-based screening method to take into consideration the predominant genotypes circulating in the country. The role of multiple HPV infections in high-grade cervical lesions entails further study in Ethiopia. [ABSTRACT FROM AUTHOR]

Objective To compare the clearance rate of high-risk human papillomavirus (HR-HPV) in patients with a high-grade squamous intraepithelial lesion (HSIL) 12 months after focused ultrasound (FUS) or loop electrosurgical excision procedure (LEEP), and analyze the influencing factors. Methods A retrospective cohort was established in HSIL patients with HR-HPV infection treated with FUS or LEEP from 2015 to 2019. The cohort consisted of 321 patients under 30 years of age, of which 119 patients received FUS and 202 patients received LEEP. The Cox regression model was used to identify the influencing factors for HR-HPV clearance. Kaplan–Meier method was applied to estimate the efficacy of FUS and LEEP in HR-HPV clearance, and the log-rank test was used to compare the efficacy difference between FUS and LEEP. Results Multivariate Cox regression analysis showed that both FUS and LEEP were independent influencing factors for HR-HPV clearance. HR-HPV cleared faster in the FUS group than in the LEEP group [the median time to HR-HPV clearance: 6 months in the FUS group (95% CI: 5.492–6.508) and 6 months in the LEEP group (95% CI: 5.734–6.266), p = 0.021]. The HR-HPV clearance rates at 6 and 12 months were 54.6% and 94.1% respectively in the FUS group, and 50.5% and 79. 2%, respectively in the LEEP group (p = 0.001 at 6 months, p = 0.000 at 12 months). Conclusions For HPV-positive HSIL patients under 30, FUS had a better HR-HPV clearance effect than LEEP 1 year after treatment. FUS may be a viable modality for the treatment of young HSIL patients.