Search

Background: High-grade anal intraepithelial squamous lesion is significantly prevalent among men who have sex with men and are infected with the human immunodeficiency virus (HIV). This condition-the precursor to anal cancer-significantly increases the risk of developing it. Conversely, low-grade anal intraepithelial squamous typically follow a benign course and usually regress spontaneously., Materials and Methods: To describe a population of men who have sex with men living with HIV followed in a specialized anal cancer screening unit we conducted an observational, retrospective, and single-center study., Results: Ninety-four patients were analyzed, with a mean age of 39±9 years, and a 87% positivity rate for high-risk human papillomavirus (HR-HPV). At the initial visit, 47% presented with low-grade squamous intraepithelial lesions. The progression rate to high-grade squamous intraepithelial lesion was 37.2 per 100,000 patients/year. None of the patients developed anal cancer. Tobacco and alcohol consumption were associated with this progression., Discussion: In this series, longer duration of HIV infection, tobacco and alcohol use and the presence of HR-HPV were significantly associated with the occurrence of high-grade intraepithelial lesions. A lower risk of progression was seen in patients with higher education., Conclusion: In men who have sex with men living with HIV, the association of factors such as smoking, alcohol, the presence of HR-HPV and an increased burden of human papillomavirus disease makes these patients more susceptible to develop high-grade anal squamous lesions., (Copyright © 2024. Publicado por Elsevier España, S.L.U.)

We present the findings of assessing the expression levels of extracellular TLR2 and TLR4 and intracellular TLR3 and TLR8 correlating with the severity of clinical manifestations of HPV infection. A total of 199 women took part in a single-center prospective comparative research study on TLR2, TLR3, TLR4 and TLR8 expression in HPV-related cervical lesions. TLRs' mRNA expression was analyzed using real-time reverse transcription polymerase chain reaction (RT-PCR). Our results indicate the potential significance of TLR3, TLR4 and TLR8 in responding to HPV infection and its progression to SILs and CC, highlighting the importance of HPV polyinfection in relation to TLR4 and TLR8.

Introduction: Dual immunostaining for p16/Ki67 is FDA-approved for use on liquid-based cervical cytology specimens; however, the utility of dual staining in anal cytology especially for ASCUS risk stratification is not well established., Methods: We investigated dual staining performance on anal cytology specimens and correlated with subsequent cytologic interpretation, high-risk HPV status, and anal biopsy results. Dual staining for p16/Ki-67 was performed on all liquid-based anal cytology specimens from December 2021 to June 2022 (n = 43)., Results: Three patients had high grade squamous intraepithelial lesion (HSIL/AIN2-3) on biopsy; dual staining was positive in all three cases. All HR-HPV negative cases were negative for dual staining. Among the 12 ASCUS samples with subsequent anal biopsy results all also had HR-HPV testing. Due to small sample size of cases with squamous intraepithelial lesion (SIL) diagnosed on biopsy, the sensitivity and positive predictive value was not calculated. However, the specificity and negative predictive value of p16/Ki-67 dual staining for SIL of any grade on biopsy were 1 (95% CI: 0.66-1) and 0.9 (95% CI: 0.65-0.97) respectively, whereas the specificity and negative predictive value of HR-HPV testing for SIL of any grade on biopsy were 0.44 (95% CI: 0.14-0.79) and 0.8 (95% CI: 0.41-0.96) respectively., Conclusion: Dual p16/Ki-67 staining indicates transforming HPV infection and could help serve as an ancillary test for risk stratification for atypical anal cytology specimens. Among ASCUS samples, dual staining was specific for SIL of any grade with a high negative predictive value and therefore could be useful in clinical practices with limited availability for follow-up care., (© 2024 Wiley Periodicals LLC.)

Background: High-grade anal intraepithelial squamous lesion is significantly prevalent among men who have sex with men and are infected with the human immunodeficiency virus (HIV). This condition-the precursor to anal cancer-significantly increases the risk of developing it. Conversely, low-grade anal intraepithelial squamous typically follow a benign course and usually regress spontaneously., Materials and Methods: To describe a population of men who have sex with men living with HIV followed in a specialized anal cancer screening unit we conducted an observational, retrospective, and single-center study., Results: Ninety-four patients were analyzed, with a mean age of 39±9 years, and a 87% positivity rate for high-risk human papillomavirus (HR-HPV). At the initial visit, 47% presented with low-grade squamous intraepithelial lesions. The progression rate to high-grade squamous intraepithelial lesion was 37.2 per 100,000 patients/year. None of the patients developed anal cancer. Tobacco and alcohol consumption were associated with this progression., Discussion: In this series, longer duration of HIV infection, tobacco and alcohol use and the presence of HR-HPV were significantly associated with the occurrence of high-grade intraepithelial lesions. A lower risk of progression was seen in patients with higher education., Conclusion: In men who have sex with men living with HIV, the association of factors such as smoking, alcohol, the presence of HR-HPV and an increased burden of human papillomavirus disease makes these patients more susceptible to develop high-grade anal squamous lesions., (Copyright © 2024. Publicado por Elsevier España, S.L.U.)

Introduction: Human papilloma virus (HPV) is the most common sexually transmitted infection worldwide. Cervicovaginal microbiota plays an important role in HPV infection and is associated with the development of squamous intraepithelial lesions (SIL). The natural history of cervical cancer involves reversible changes in the cervical tissue from a normal state, in which no neoplastic changes are detected in the squamous epithelium, to varying states of cellular abnormalities that ultimately lead to cervical cancer. Low-grade SIL (LSIL), like another cytological category - atypical squamous cells of undetermined significance (ASCUS), may progress to high-grade SIL (HSIL) and invasive cervical cancer or may regress to a normal state., Methods: In this work, we studied cervical canal microbiome in 165 HPV-positive and HPV-negative women of a reproductive age with ASCUS [HPV(+) n  = 29; HPV(-) n  = 11], LSIL [HPV(+) n  = 32; HPV(-) n  = 25], HSIL [HPV(+) n  = 46], and the control group with negative for intraepithelial lesion malignancy (NILM) [HPV(-) n  = 22]., Results and Discussion: HPV16 is the most prevalent HPV type. We have not found any differences between diversity in studied groups, but several genus [like Prevotella ( p -value = 0.026), Gardnerella ( p -value = 0.003), Fannyhessea ( p -value = 0.024)] more often occurred in HSIL group compared by NILM or LSIL regardless of HPV. We have found statistically significant difference in occurrence or proportion of bacterial genus in studied groups. We also identified that increasing of the ratio of Lactobacillus iners or age of patient lead to higher chance to HSIL, while increasing of the ratio of Lactobacillus crispatus lead to higher chance to LSIL. Patients with a moderate dysbiosis equally often had either of three types of vaginal microbial communities (CST, Community State Type) with the prevalence of Lactobacillus crispatus (CST I), Lactobacillus gasseri (CST II), and Lactobacillus iners (CST III); whereas severe dysbiosis is linked with CST IV involving the microorganisms genera associated with bacterial vaginosis and aerobic vaginitis: Gardnerella , Fannyhessea, Dialister, Sneathia, Anaerococcus, Megasphaera, Prevotella, Finegoldia, Peptoniphilus, Porphyromonas, Parvimonas , and Streptococcus ., Competing Interests: The 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 Peremykina, Cheranev, Krivoy, Andreev, Repinskaia, Asaturova, Korostin, Rebrikov and Bayramova.)

The lack of human-derived in vitro models that recapitulate cervical pre-cancerous lesions has been the bottleneck in researching human papillomavirus (HPV) infection-associated pre-cancerous lesions and cancers for a long time. Here, a long-term 3D organoid culture protocol for high-grade squamous intraepithelial lesions and cervical squamous cell carcinoma that stably recapitulates the two tissues of origin is described. Originating from human-derived samples, a small biobank of cervical pre-tumoroids and tumoroids that faithfully retains genomic and transcriptomic characteristics as well as the causative HPV genome is established. Cervical pre-tumoroids and tumoroids show differential responses to common chemotherapeutic agents and grow differently as xenografts in mice. By coculture organoid models with peripheral blood immune cells (PBMCs) stimulated by HPV antigenic peptides, it is illustrated that both organoid models respond differently to immunized PBMCs, supporting organoids as reliable and powerful tools for studying virus-specific T-cell responses and screening therapeutic HPV vaccines. In this study, a model of cervical pre-cancerous lesions containing HPV is established for the first time, overcoming the bottleneck of the current model of human cervical pre-cancerous lesions. This study establishes an experimental platform and biobanks for in vitro mechanistic research, therapeutic vaccine screening, and personalized treatment for HPV-related cervical diseases., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Programmed death-ligand 1 (PD-L1) is overexpressed in cervical carcinoma, hindering tumor destruction. The aim of this study was to assess PD-L1 expression by immunohistochemistry in cervical squamous cell carcinoma (SCC) and squamous intraepithelial lesions (SILs) from human immunodeficiency virus-positive (HIV+) and human immunodeficiency virus-negative (HIV-) patients. A total of 166 SCC and SIL samples of HIV+ and HIV- patients were included and analyzed for PD-L1 expression through tumor proportion score (TPS), and results were stratified in five TPS groups using SP263 antibody and, combined positive score (CPS) using 22C3 antibody. In cohort 1 (SP263 clone), all HIV+ patients were negative for intraepithelial lesion or malignancy (NILM), and low-grade squamous intraepithelial lesions (LSILs) scored < 1; and 87.5% of high-grade squamous intraepithelial lesions (HSILs) adjacent to SCC, 19% of HSILs non-adjacent to SCC, and 69% of SCCs scored ≥ 1 (15.4% scored 5). In HIV- patients, all NILM, LSILs, HSILs adjacent to SCC, and two HSILs non-adjacent to SCC scored < 1. SCC: 88.2% scored ≥ 1 and 5.9% scored 5. In cohort 2 (SP263 and 22C3 clones), 16.7% of HIV+ patients with SCC were positive with both clones, CPS ≥ 1 (22C3) or score 5 (≥ 50%) (SP263), showing no significant differences in positivity between both clones. These results indicate that a relatively low percentage of SCCs (16.7%; both in HIV+ and in HIV- patients) express PD-L1 (TPS ≥ 50% and CPS > 1), which may be due to some samples being archival material, sample characteristics, or use of different methodologies, highlighting the need for standardization of PD-L1 assessment in SCC of the cervix. The fact that PD-L1 is overexpressed in SILs of HIV+ patients suggests potential additional applications for immunotherapy in this disease., (© 2023. The Author(s).)

Objective: In this study, we established a Sprague-Dawley rat model of vulvar squamous intraepithelial lesions and investigated the impact of focused ultrasound on the expression of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and mutant type p53 (mtp53) in the vulvar skin of rats with low-grade squamous intraepithelial lesions (LSIL)., Materials and Methods: The vulvar skin of 60 rats was treated with dimethylbenzanthracene (DMBA) and mechanical irritation three times a week for 14 weeks. Rats with LSIL were randomly allocated into the experimental group or the control group. The experimental group was treated with focused ultrasound, while the control group received sham treatment., Results: After 14 weeks treatment of DMBA combined with mechanical irritation, LSIL were observed in 44 (73.33%) rats, and high-grade squamous intraepithelial lesions (HSIL) were observed in 14 (23.33%) rats. 90.91% (20/22) of rats showed normal pathology and 9.09% (2/22) of rats exhibited LSIL in the experimental group at four weeks after focused ultrasound treatment. 22.73% (5/22) of rats exhibited LSIL, 77.27% (17/22) of rats progressed to HSIL in the control group. Compared with the control-group rats, the levels of HIF-1α, VEGF and mtp53 were significantly decreased in experimental-group rats ( p  < 0.05)., Conclusions: These results indicate that DMBA combined with mechanical irritation can induce vulvar squamous intraepithelial lesion in SD rats. Focused ultrasound can treat LSIL safely and effectively, prevent the progression of vulvar lesions, and improve the microenvironment of vulvar tissues by decreasing the localized expression of HIF-1α, VEGF, and mtp53 in rats.

Cervical squamous intraepithelial lesions (SILs) may present a diagnostic challenge due to their morphological similarity to benign conditions and variability in interpretation, necessitating the exploration of objective biomarkers to aid in their identification and grading. This study evaluates the immunohistochemical markers Carbonic Anhydrase IX (CAIX) and ProEx-C to assess their diagnostic potential in cervical SILs. We retrospectively identified 56 SIL cases, including 20 low-grade SILs (LSIL) and 36 high-grade SILs (HSIL), alongside a control group of nine chronic cervicitis cases. Immunohistochemical staining was performed on formalin-fixed, paraffin-embedded tissue blocks, and the sensitivity and specificity of CAIX and ProEx-C were evaluated for detecting and grading SILs. CAIX exhibited a sensitivity of 64.3 % and a specificity of 100 % for detecting SILs. ProEx-C staining displayed a sensitivity of 66.1 % and a specificity of 100 % for detecting SILs. The combination of CAIX and ProEx-C staining increased the sensitivity for detecting SILs to 80.4 % without compromising the specificity. These markers alone or in combination were not found to be significant in distinguishing LSIL from HSIL. Both markers showed positivity in benign endocervical and squamous epithelium in high rates. In conclusion, CAIX and ProEx-C are valuable immunohistochemical markers for detecting SILs in cervical specimens, with high sensitivity and specificity. Further research is needed to elucidate their roles in cervical carcinogenesis and their relationship with HPV infection., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Cervical cytology has been an integral part of cervical cancer screening since the mid-20th century with the implementation of screening protocols utilising Pap testing. During that time, cervical cancer has gone from the leading cause of cancer deaths in women to not even appearing in the top 10 causes of US cancer deaths. However, despite its long and widespread use, cervical cytology remains a diagnostically challenging area in the practice of cytopathology. Of particular importance for diagnosticians is the accurate diagnosis of high-grade squamous intraepithelial lesions (HSILs), given the significant risk of progression to invasive cervical cancer and the importance to patient management. Therefore, this review is presented in order to highlight the diagnostic features of HSIL, its various appearances, and important benign and neoplastic differential considerations with an emphasis on morphological clues that can aid in distinguishing between these different processes., (© 2023 John Wiley & Sons Ltd.)

Objective: Cervical squamous intraepithelial lesion (SIL) and cervical cancer are major threats to females' health and life in China, and we aimed to estimate the economic burden associated with their diagnosis and treatment., Methods: A nationwide multicenter, cross-sectional, hospital-based survey was conducted in 26 qualified hospitals across seven administrative regions of China. We investigated females who had been pathologically diagnosed with SIL and cervical cancer, and included five disease courses ("diagnosis", "initial treatment", "chemoradiotherapy", "follow-up" and "recurrence/progression/metastasis") to estimate the total costs. The median and interquartile range (IQR) of total costs (including direct medical, direct non-medical, and indirect costs), reimbursement rate by medical insurance, and catastrophic health expenditures in every clinical stage were calculated., Results: A total of 3,471 patients in different clinical stages were analyzed, including low-grade SIL (LSIL) (n=549), high-grade SIL (HSIL) (n=803), cervical cancer stage IA (n=226), IB (n=610), IIA (n=487), IIB (n=282), III (n=452) and IV (n=62). In urban areas, the estimated total costs of LSIL and HSIL were [Formula: see text]1,637.7 (IQR: [Formula: see text]956.4-[Formula: see text]2,669.2) and [Formula: see text]2,467.1 (IQR: [Formula: see text]1,579.1-[Formula: see text]3,762.3), while in rural areas the costs were [Formula: see text]459.0 (IQR: [Formula: see text]167.7-[Formula: see text]1,330.3) and [Formula: see text]1,230.5 (IQR: [Formula: see text]560.6-[Formula: see text]2,104.5), respectively. For patients with cervical cancer stage IA, IB, IIA, IIB, and III-IV, the total costs were [Formula: see text]15,034.9 (IQR: [Formula: see text]11,083.4-[Formula: see text]21,632.4), [Formula: see text]19,438.6 (IQR: [Formula: see text]14,060.0-[Formula: see text]26,505.9), [Formula: see text]22,968.8 (IQR: [Formula: see text]16,068.8-[Formula: see text]34,615.9), [Formula: see text]26,936.0 (IQR: [Formula: see text]18,176.6-[Formula: see text]41,386.0) and [Formula: see text]27,332.6 (IQR: [Formula: see text]17,538.7-[Formula: see text]44,897.0), respectively. Medical insurance covered 43%-55% of direct medical costs for cervical cancer patients, while the coverage for SIL patients was 19%-43%. For most cervical cancer patients, the expense was catastrophic, and the extent of catastrophic health expenditure was about twice large for rural patients than that for urban patients in each stage., Conclusions: The economic burden of SIL and cervical cancer in China is substantial, with a significant proportion of the costs being avoidable for patients with LSIL. Even for those with medical insurance, catastrophic health expenditures are also a major concern for patients with cervical cancer, particularly for those living in rural areas., (Copyright ©2023 Chinese Journal of Cancer Research. All rights reserved.)

Human papillomavirus (HPV) infection represents a significant global health concern owing to its role in the etiology of conditions ranging from benign low-grade lesions to cancers of the cervix, head and neck, anus, vagina, vulva, and penis. Prophylactic vaccination programs, primarily targeting adolescent girls, have achieved dramatic reductions in rates of HPV infection and cervical cancer in recent years. However, there is a clear demand for a strategy to manage the needs of the many people who are already living with persistent HPV infection and/or HPV-associated conditions. Unlike prophylactic vaccines, which act to prevent HPV infection, therapeutic vaccination presents an opportunity to induce cellular immunity against established HPV infections and lesions and prevent progression to cancer. Several HPV vaccines are undergoing clinical development, using a range of platforms. Peptide- or protein-based vaccines, vector-based vaccines, whole-cell vaccines, and nucleic acid vaccines each offer relative merits and limitations for the delivery of HPV antigens and the subsequent generation of targeted immune responses. There has been particular interest in DNA-based vaccines, which elicit both cellular and humoral immune responses to provide long-lasting immunity. DNA vaccines offer several practical advantages over other vaccine platforms, including the potential for rapid and scalable manufacturing, targeting of many different antigens, and potential for repeat boosting. Furthermore, unlike vectored approaches, DNA vaccines are thermostable over extended time periods, which may enable shipping and storage. Several delivery strategies are available to address the main challenge of DNA vaccines, namely their relatively low transfection efficiency. We review the latest clinical data supporting the development of DNA vaccines and reflect on this exciting prospect in the management of HPV-related disease., Competing Interests: Declaration of competing interest JMS and MPM are employees of INOVIO Pharmaceuticals., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: A large-sample study focusing on VIN lesions of a more precise thickness is needed to help guide clinical treatment. This study aimed to investigate the depth of vulvar intraepithelial neoplasia (VIN) and involved skin appendages to provide evidence for laser surgery., Methods: The study retrospectively enrolled and analyzed the clinical characteristics of VIN patients in the obstetrics and gynecology department of a university hospital between January 1, 2019 and December 30, 2021. The study further explored the thickness of epithelium and skin appendages of 285 women with low-grade VIN (VIN1) and 285 women with high-grade VIN (VIN2/3)., Results: The study included 1,139 (80%) VIN1 and 335 (20%) VIN2/3 cases. The VIN1 and VIN2/3 groups showed a significant difference in human papillomavirus infection (P<0.01) but not in cytology (P = 0.499). Most (89.90%, 1,325) cases occurred in one area of the vulva, whereas 10.11% were multifocal. VIN commonly occurred on the posterior fourchette (76.85%), labia majora (11.61%), and labia minora (9.92%). The VIN2/3 group reported a significantly higher positive rate for concurrent cervical and vaginal intraepithelial neoplasia (160 of 285) than the VIN1 group (321 of 953) (P=0.000). The involved epithelial thicknesses in VIN2/3 and VIN1 were 0.69 ± 0.44 and 0.49 ± 0.23 mm, respectively, both of which were greater than the corresponding noninvolved epithelial thickness (0.31 ± 0.19 and 0.32 ± 0.10 mm, P<0.001 and P<0.001, respectively). In cases of appendage involvement, the VIN thickness was 1.98 ± 0.64 mm., Conclusions: VIN thickness was generally ≤1 mm for the superficial lesions in non-hairy areas. However, for lesions extending onto hairy areas, the thickness was approximately 3 mm, leading to the destruction of involved skin appendages., Competing Interests: The 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 © 2023 Xiao, Chen, Xiao, Sui, Wang and Cong.)

Objectives: The 2019 American Society of Colposcopy and Cervical Pathology management guidelines recommend that patients with an unsatisfactory Papanicolaou (Pap) test (UPT) and negative human papillomavirus (HPV) cotest undergo repeat age-based screening in 2 to 4 months. The rationale is that a negative HPV test in the setting of an UPT may reflect an inadequate sample and therefore should not be interpreted as truly "negative." For patients 25 years and older who are cotested, if HPV is positive for the 16 or 18 genotypes, direct referral for colposcopy is recommended. Our study aimed to determine if a negative HPV cotest result is predictive of the absence of a high-grade squamous intraepithelial lesion (HSIL) and whether these patients may be called back for repeat testing at an interval longer than 2 to 4 months., Methods: Follow-up cervical cytology and biopsy results in women with UPT and HPV cotests from January 2017 to December 2021 were collected. Original UPT and HPV cotest results were correlated with the follow-up Pap and biopsy results., Results: There were 1,496 (2.28%) UPT cases out of 65,641 total Pap tests. Among the 1,496 UPT cases, 1,010 (67.5%) had HPV cotesting; 676 (45.1%) were followed by repeat Pap or biopsy within 4 months and 850 (56.8%) within 12 months. The total follow-up rate was 81%, with a range of 3 days to 36 months. The HSIL rate in HPV-positive cases was 5.7% (3/53) vs 0.4% (2/539) (P = .006) in HPV-negative cases. In UPT, HPV cotesting showed negative predictive values for low-grade and high-grade squamous intraepithelial lesion detection of 98.5% and 99.6%, respectively, while positive predictive values were 19% and 5.7%., Conclusions: A negative HPV cotest in individuals with UPT predicted the lack of HSIL in our study. Compliance with the recommended follow-up time of 2 to 4 months for women with UPT was low (45.1%). Our study suggests that women with UPT and negative HPV cotest may be safely called back at an interval longer than 4 months., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: P16 INK4A is a surrogate signature compensating for the specificity and/or sensitivity deficiencies of the human papillomavirus (HPV) DNA and Papanicolaou smear (Pap) co-test for detecting high-grade cervical squamous intraepithelial lesions or worse (HSIL+). However, traditional p16INK4A immunostaining is labour intensive and skill demanding, and subjective biases cannot be avoided. Herein, we created a high-throughput, quantitative diagnostic device, p16INK4A flow cytometry (FCM) and assessed its performances in cervical cancer screening and prevention., Methods: P16 INK4A FCM was built upon a novel antibody clone and a series of positive and negative (p16 INK4A -knockout) standards. Since 2018, 24 100-women (HPV-positive/-negative, Pap-normal/-abnormal) have been enrolled nationwide for two-tier validation work. In cross-sectional studies, age- and viral genotype-dependent expression of p16 INK4A was investigated, and optimal diagnostic parameter cut-offs (using colposcopy and biopsy as a gold standard) were obtained. In cohort studies, the 2-year prognostic values of p16 INK4A were investigated with other risk factors by multivariate regression analyses in three cervicopathological conditions: HPV-positive Pap-normal, Pap-abnormal biopsy-negative and biopsy-confirmed LSIL., Results: P16 INK4A FCM detected a minimal ratio of 0.01% positive cells. The p16 INK4A -positive ratio was 13.9 ± 1.8% among HPV-negative NILM women and peaked at the ages of 40-49 years; after HPV infection, the ratio increased to 15.1 ± 1.6%, varying with the carcinogenesis of the viral genotype. Further increments were found in women with neoplastic lesions (HPV-negative: 17.7 ± 5.0-21.4 ± 7.2%; HPV-positive: 18.0 ± 5.2-20.0 ± 9.9%). Extremely low expression of p16 INK4A was observed in women with HSILs. As the HPV-combined double-cut-off-ratio criterion was adopted, a Youden's index of 0.78 was obtained, which was significantly higher than that (0.72) of the HPV and Pap co-test. The p16 INK4A -abnormal situation was an independent HSIL+ risk factor for 2-year outcomes in all three cervicopathological conditions investigated (hazard ratios: 4.3-7.2)., Conclusions: FCM-based p16 INK4A quantification offers a better choice for conveniently and precisely monitoring the occurrence of HSIL+ and directing risk-stratification-based interventions., (© 2022 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Aim: To identify DNA methylation markers for triage in a cohort of human papillomavirus-positive (HPV + ) women. Methods: The methylation markers were identified and evaluated for the detection of cervical high-grade squamous intraepithelial lesions (HSILs) or cervical cancer (collectively referred to as 'HSIL+') in HPV + women (n = 692). Results: Combined PAX1 / ST6GALNAC5 methylation testing yielded HSIL+ sensitivity of 0.838 and 0.818, with a specificity of 0.827 and 0.810, in the training and test sets, respectively. For cervical cancer, the specificity and sensitivity were 0.969 and 1.000 in the training set and 0.967 and 0.875 in the test set. Moreover, the combined marker methylation test (0.86; 77/90) was more sensitive than the cytology (0.31; 28/90) for HSIL+. Conclusion: The combined PAX1 / ST6GALNAC5 marker may have clinical application for detecting HSIL+ in HPV + women undergoing screening.

Despite the knowledge of etiological association with high-risk human papilloma viruses and high-risk patient cohorts, the incidence of anal squamous cell carcinoma has continued to rise. The known precursor lesion (in particular, high-grade squamous intraepithelial lesion) makes it amenable to screening and surveillance strategies. However, the diagnosis of anal intraepithelial neoplasia suffers from interpretation challenges leading to high interobserver variability, along with numerous differential diagnoses and lingering terminology issues. Proper treatment of anal lesions requires accurate diagnosis, and while a variety of modalities are available for treatment, the rate of recurrence remains high and each modality has its own set of side effects and complications. The aim of this review article is to outline the diagnostic considerations and provide practical tips for diagnosing anal squamous intraepithelial lesions., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background and Aim: The natural history of cervical cancer is unique that it is preceded by a precancerous condition for a long time. Morphometry as a tool can be used in early and accurate diagnosis of these precancerous and cancerous lesions. The present study aims at assessing the utility of cellular and nuclear morphometry in differentiating squamous cell abnormality from benign conditions and also differentiating the categories of squamous cell abnormalities., Materials and Methods: Forty-eight diagnosed cases of squamous epithelial cell abnormality, that is, 10 cases each of atypical squamous cell of undetermined significance (ASC-US), low-grade squamous intraepithelial lesion (LSIL), high-grade SIL (HSIL), and squamous cell carcinoma (SCC) and eight cases of ASC-H (ASC cannot exclude HSIL), were made the sample population and compared with a control population of 10 cases of negative for intraepithelial lesion or malignancy (NILM). Parameters like nuclear area (NA), nuclear perimeter (NP), nuclear diameter (ND), nuclear compactness (NC), cellular area (CA), cellular diameter (CD), cellular perimeter (CP), and nucleocytoplasmic (N/C) ratio were used., Results: There was a significant difference in the six groups of squamous cell abnormality based on NA, NP, ND, CA, CP, and CD ( P < 0.05) using one-way analysis of variance. Nuclear morphometry parameters like NA, NP, and ND were found to be the maximum for HSIL, followed by LSIL, ASC-H, ASC-US, SCC, and NILM groups in decreasing order. The mean CA, CP, and CD were found to be the maximum for NILM, followed by LSIL, ASC-US, HSIL, ASC-H, and SCC in decreasing order. On post hoc analysis, the lesions can be divided into three groups: NILM/normal; ASC-US and LSIL; and ASC-H, HSIL, and SCC, based on N/C ratio., Conclusion: In cervical lesions, holistic parameter of cytonucleomorphometry should be taken rather than taking nuclear morphometry only. N/C ratio is a highly statistically significant parameter that can differentiate between low-grade lesions and high-grade lesions., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Cytology.)

Objectives: Long-term exposure to the human papillomavirus (HPV) is a known cause of squamous intraepithelial lesions that lead to cervical cancer. The loop electrosurgical excision procedure (LEEP) conization is an established treatment method. According to the latest recommendations, we present a paper to evaluate the effectiveness of various diagnostic methods of squamous intraepithelial lesions., Material and Methods: We analyzed 229 patients who reported to District Public Hospital in Poznan to undergo LEEP conization in 2019-2021 during the SARS-CoV-2 Pandemic. The analysis included Pap smear/liquid-based cytology, HPV genotyping, colposcopy with targeted biopsy and LEEP-conization. We offered post-treatment HPV vaccination and, as a follow-up, performed HPV re-genotyping after six months., Results: In total, 89.1% of patients were HPV-positive. The coloscopy-directed biopsy (CDB) results show that almost 70% of the patients had high-grade intraepithelial lesions (HSIL). The diagnosis obtained by LEEP-conization showed that half of the women were diagnosed with HSIL and one-third with the low-grade squamous intraepithelial lesion (LSIL). The sensitivity of Pap smear/LBC accounted for 93.7% and was lower than for CDB, which reached 95.1%. Both diagnostic methods tend to underestimate the final diagnosis., Conclusions: The inclusion of a colposcopic examination in an in-depth diagnostic process in women with abnormal Pap smear results facilitates the identification of patients requiring therapeutic intervention. LEEP-conization may be used without the primary biopsy. It applies to multiparous women in the perimenopausal period, extensive abnormalities, discrepancies in test results, extensive visible abnormalities, and suspicion of invasive cervical cancer in the colposcopic examination.

Objective: The aim of the present study was to evaluate the impact of the mode of delivery on the natural evolution of cervical squamous intraepithelial lesions in pregnant patients., Methods: Α systematic search was conducted in Medline (1966-2021), Cochrane Central Register of Controlled Trials CENTRAL (1999-2021), Scopus (2004-2021), Google Scholar (2004-2021) and Clinicaltrials.gov (2008-2021) along with the reference lists of electronically retrieved full-text papers. All the studies that investigated the correlation of the mode of delivery with the natural evolution of cervical squamous intraepithelial lesions of patients during pregnancy, were included in the present meta-analysis., Results: Eight retrospective studies were finally included, comprising 813 patients whose premalignant lesions were evaluated cytologically, of whom 685 delivered via the vaginal route, and 233 patients whose squamous intraepithelial lesions were evaluated histologically, of whom 162 delivered vaginally. The methodological quality of the included studies ranged between moderate and serious. Regression rates were comparable among women that delivered with caesarean section compared to patients that delivered vaginally, both in the cytological (OR 1.32, 95% CI 0.56, 3.12) and in the histological evaluation (OR 1.87, 95% CI 0.50, 6.96) of the lesions. Subgroup analysis revealed consistent results for all subgroups of premalignant lesions. Finally, the results observed for both the persistence and the progression rates of these lesions were proportional., Conclusion: Our meta-analysis suggests that the delivery mode does not alter the natural evolution of squamous intraepithelial lesions in pregnant women and therefore their presence should not determine the mode of delivery., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest to disclose., (Copyright © 2022. Published by Elsevier Masson SAS.)

Introduction: This study aimed to analyse the relationship between clinicopathological factors in cervical intraepithelial lesions and abnormal colposcopic findings., Material and Methods: Thirty high-grade squamous intraepithelial lesion (HSIL) and thirty low-grade squamous intraepithelial lesion (LSIL) patients who underwent biopsy due to abnormal colposcopic findings were included in the study. The immunoreactivity of CD3, CD4, CD5, CD8, and PD-1 was analysed immunohistochemically in tumor-infiltrating lymphocytes (TILs) and stromal lymphocytes., Results: In TILs, CD3, CD4, CD5, CD8, and PD-1 were highly stained in 20/30 (66.6%), 16/30 (53.3%), 15/30 (50.0%), 24/30 (80.0%), and 13/30 (43.3%) of the cases for the HSIL group, while 7/30 (23.3%), 4/30 (13.3%), 5/30 (16.6%), 9/30 (30.0%), and 5/30 (16.6%) were in the LSIL group, respectively. CD3, CD4, CD5, CD8, and PD-1 immunostainings for TILs were higher in the HSIL group (p=0.001, p=0.001, p=0.006, p˂0.001, p=0.024, respectively). Only PD-1 was significantly higher in lymphocytes in the stroma (p=0.001)., Conclusions: CD3, CD4, and CD8 also show a positive correlation with the Ki-67 proliferation index. CD3, CD4, CD5, and CD8 may contribute to PD-1-mediated tumour control. Immunohistochemical staining plays a key role in evaluating the tumour microenvironment., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Atigan et al.)

Background: Cervical cancer is still a public health problem in many developing countries, like Nigeria. HIV infection makes HPV infections last longer, progress to squamous intraepithelial lesion of the cervix, and eventually lead to invasive cervical cancer., Objective: Find out how often squamous intraepithelial lesions (SIL) happen and what causes them in HIV-positive women in Sagamu, southwest Nigeria., Methods: A cross-sectional study was done with 165 women with HIV and 165 women without HIV. Pap smears were done on all of the people in the study. The data was looked at with IBM-SPSS Windows v. 23., Results: Both groups were about the same age and had the same number of children (P=0.194 and P=0.388, respectively). The participants' average age (SD) was 36.8 (5.6), and the median number of children they had was 3. HIV-positive women were much more likely to have an abnormal cytology smear (24.8%) than HIV-negative women (7.3%) (2 = 18.904, P 0.001). There wasn't a link between having HIV and the severity of cervical lesions (2 = 3.66, P = 0.162). A CD4 cell count of less than 350 cells/mm 3 was found to be a strong predictor of an abnormal cervical cytological smear in HIV-positive women (AOR: 25.5; CI: 8.8-73.5; P 0.001)., Conclusion: In Sagamu, Nigeria, the number of HIV-positive women with SIL of the cervix was much higher than the number of HIVnegative women with SIL of the cervix. HIV-positive women, especially those with a low number of CD4 cells, need cervical smear tests more often. This will make sure that pre-invasive lesions are found and treated as soon as possible., (©Copyright: the Author(s).)

Infection by high-risk human papillomavirus (HPV) causes genetic alterations in host cervical cells with consequent changes in gene expression affecting downstream molecular pathways, leading to the development of cervical cancer. In this exploratory study, we aimed to identify the perturbed cellular pathways during the various stages of cervical carcinogenesis. Total RNA was extracted from three formalin-fixed paraffin-embedded (FFPE) samples each of normal cervix, HPV-infected low-grade squamous intraepithelial lesion (LSIL), high-grade SIL (HSIL) and squamous cell carcinoma (SCC). Gene expression profiling was performed using the 770-gene panel from NanoString nCounter® PanCancer Pathways Panel to identify differentially expressed genes (DEGs) and significantly associated pathways in each stage of cervical cancer development. We identified 121 DEGs involved in cervical carcinogenesis. In the transformation from normal cells to LSIL, the MAPK, transcriptional misregulation and JAK-STAT pathways are implicated, while IL1B may promote inflammation and indirectly activates MMP9, resulting in collagen breakdown and cell migration. The cell cycle - apoptosis pathway with upregulation of E2F1 and MCM2, and DNA repair genes BRCA2-BRIP1 and FANCA are crucial during the progression from LSIL to HSIL. In the final stage of progression to SCC, the cell cycle and signaling pathways, as well as upregulation of c-MYC appear essential. In conclusion, archived FFPE-derived tissue samples are a valuable resource for gene expression profiling. The postulated dysregulated pathways and genes provide a guide of the molecular mechanisms that may be involved in the development of HPV-associated cervical cancer, for further investigation and validation studies., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Purpose: This study aimed to determine the potential clinical use of dynamic thiol-disulfide balance in cases with preinvasive lesions of the cervix., Methods: One hundred and sixteen patients with high-grade squamous intraepithelial lesion, 100 patients with low-grade squamous intraepithelial lesion, and 110 healthy controls were enrolled in the study. A fully automated colorimetric system was used to determine the levels of thiol-disulfide parameters. The ischemia-modified albumin, total oxidant-antioxidant capacity, and oxidative stress index of the retrieved cases were further analyzed., Results: Native thiol and total thiol levels are significantly lower in the high-grade squamous intraepithelial lesion group according to control group (p: 0.004 and 0.015, respectively). Disulfide level is significantly increased in the high-grade squamous intraepithelial lesion group compared to control group (p: 0.004). Oxidative stress index levels in high-grade squamous intraepithelial lesion group were observed as significantly higher according to the control group (p: 0.014). Ischemia-modified albumin levels in the high-grade squamous intraepithelial lesion group were observed as significantly higher compared to the control group (p: 0.020). Disulfide levels are positively correlated with risk type of Human papillomavirus (r: 0.420, p < 0.001)., Conclusion: The analysis of dynamic thiol-disulfide balance revealed considerable oxidative damage in patients with Human papillomavirus-related cervical precursor lesions compared to women with ordinary cytology specimens. Therefore, investigation of thiol-disulfide balance with presented method represents a new promising test for early diagnosis and management of women at high risk for cervical cancer., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: High-risk human papillomavirus (HR-HPV) infection is the main cause of cervical cancer, but additional alterations are necessary for its development. Abnormal DNA methylation has an important role in the origin and dissemination of cervical cancer and other human tumors. In this work, we analyzed the methylation of eight genes (AJAP1, CDH1, CDH13, MAGI2, MGMT, MYOD1, RASSF1A and SOX17) that participate in several biological processes for the maintenance of cell normality. We analyzed DNA methylation by methylation-specific PCR (MSP) and HPV infection using the INNO‑LiPA genotyping kit in 59 samples diagnostic of normal cervical tissue (non-SIL), 107 low-grade squamous intraepithelial lesions (LSILs), 29 high-grade squamous intraepithelial lesions (HSILs) and 51 cervical cancers (CCs)., Results: We found that all samples of LSIL, HSIL, and CC were HPV-positive, and the genotypes with higher frequencies were 16, 18, 51 and 56. In general, the genes analyzed displayed a significant tendency toward an increase in methylation levels according to increasing cervical lesion severity, except for the CDH13 gene. High CpG island methylator phenotype (CIMP) was associated with a 50.6-fold (95% CI 4.72-2267.3)-increased risk of HSIL and a 122-fold risk of CC (95% CI 10.04-5349.7)., Conclusions: We found that CIMP high was significantly associated with HSIL and CC risk. These results could indicate that CIMP together with HR-HPV infection and other factors participates in the development of HSIL and CC., (© 2022. The Author(s).)

(1) Background: There are limited data on the success of conservative treatment of high-grade cervical squamous intraepithelial lesions (HSIL) with imiquimod directly compared to standard of treatment with LLETZ. (2) Methods: Patients aged 18-40 with histological HSIL (with high-grade cervical intraepithelial neoplasia, CIN2p16+ and CIN3), were randomly assigned to treatment with imiquimod or LLETZ. The primary outcome was defined as the absence of HSIL after either treatment modality. The secondary outcomes were the occurrence of side effects. (3) Results: 52 patients were allocated in each group and were similar regarding baseline characteristics. In the imiquimod group, 82.7% of patients completed treatment, which was successful in 51.9%. All patients in the LLETZ group completed treatment, which was successful in 92.3% ( p < 0.001). In the subgroup of CIN2p16+ patients, treatment with imiquimod was not inferior to LLETZ (73.9% vs. 84.2%, p = 0.477). During and after treatment, no cases of progression to cancer were observed. Side effects and severe side effects (local and systemic) were more prevalent in the imiquimod than in the LLETZ group (88.5% vs. 44.2% ( p -value < 0.001) and 51.9% vs. 13.5% ( p -value < 0.001), respectively). (4) Conclusion: Generally, in patients with HSIL, LLETZ remains the gold standard of treatment. However, in a subgroup analysis of patients with CIN2p16+, the success rate was comparable between the two treatment modalities. Due to the prevalence of side effects, the treatment compliance with imiquimod use may, however, present a clinically important issue.

Background: The repressor element 1-silencing transcription factor (REST) is a regulator of gene expression, and the Ras association domain family member 1 A (RASSF1A) is an important tumor suppressor gene involved in cancer development. Although extensive characterization of the roles of REST and RASSF1A in cancer development have been reported in cellular models, the link between them and their possible role in the development of squamous intraepithelial lesions (SIL) and squamous cell carcinoma (SCC) of the cervix have not been explored. The aim of this study was to evaluate the expression of REST and RASSF1A in cervical cytological and histological samples from patients diagnosed with SIL or SCC and in CC-derived cell lines., Methods: We analyzed the expression of REST and RASSF1A by immunocyto/histochemistry in cervical samples from patients (n = 271) and in cancer cell lines. Data analyses were performed using the Kruskal-Wallis test and generalized linear models., Results: We identified binding sites for REST in RASSF1A and observed a significant reduction in REST and RASSF1A nuclear expression in samples from patients with high-grade SIL (HSIL) and SCC. For REST, we observed an average decrease of 334 and 423 r.u.d. for HSIL (n = 21) and SCC (n = 18) compared with non-LSIL (n = 72), whereas for RASSF1A, this decrease was 126 and 217 r.u.d., respectively (p < 0.001)., Conclusion: Our results provide evidence of the altered expression of REST and RASSF1A in SIL and SCC, with a significant decrease in HSIL, SCC, and SCC-derived cell lines; findings that can contribute to the diagnosis, prognosis, and post-treatment follow-up of patients diagnosed with SIL or SCC., Competing Interests: Conflicts of interest The authors declare that they have no conflicts of interest., (Copyright © 2020 Chang Gung University. Published by Elsevier B.V. All rights reserved.)

Background: Human papilloma virus (HPV) has been widely implicated in cervical carcinogenesis and 90% of carcinoma cervix cases are due to high-risk HPV infection. This study was done to find the high-risk HPV genotypes in the rural women of Lucknow, North India., Materials and Methods: HPV-DNA testing has been carried out in 130 cases of squamous intraepithelial lesions (SILs) of the cervix to find HPV status and type of high-risk HPV genotype infecting the rural women. These cases were collected from the rural cervical cancer screening program carried out in the villages of West Lucknow, North India., Results: HPV status in 130 SIL cases revealed HPV positivity in only 17 cases (13.1%), whereas the remaining 113 cases were HPV negative (86.9%). HPV genotypes detected in the study were HPV-18, HPV-31, HPV-33, and HPV-35. HPV positivity was found highly associated with the young and sexually active group of women complaining of vaginal discharge. High HPV infection rate was also seen with multiparity and illiteracy as majority of women attending the camps were multiparous and illiterate., Conclusions: The present study revealed highly oncogenic HPV-18 alone or in combination with multiple infections of high-risk genotypes - 31, 33, and 35 - in the rural women of Lucknow, North India. Since HPV vaccine currently available in India is for HPV-16 and HPV-18 combined, efforts should be made to make region-specific vaccine according to their prevalence in that particular state of the country to provide effective HPV vaccination., Competing Interests: None

Vaginal microbiome may have a role in HPV infection and cervical neoplasm. To explore potential vaginal microbiome biomarkers for high-grade squamous intraepithelial lesion (HSIL), and to find the best scheme to facilitate the current cervical cancer screening strategy. This study enrolled 272 women, including 83 confirmed with HSIL, 86 with HPV infection but without cervical neoplasm, and 103 without HPV infection as controls. Vaginal microbiome composition was determined by sequencing of barcoded 16S rDNA gene fragments (V4) on Illumina HiSeq2500. The relative increasing abundance of Stenotrophomonas, Streptococcus , and Pseudomonas , and a concomitant paucity of Dialister, unidentified Prevotellaceae, Faecalibacterium, Bifidobacterium , and Bacteroides , were related with HSIL, which can be used to predict the development of HISL in high-risk HPV infected patients. The relative abundance of Stenotrophomonas being over 0.0090387%, or Faecalibacterium being under 0.01420015%, or Bifidobacterium being under 0.0116183% maybe a good predictor for HSIL for those infected with HPV 16 and/or 18. The relative abundance of Stenotrophomonas being over 0.01549105%, or Streptococcus being over 0.48409585%, or Bacteroides being under 0.0296912% maybe a good predictor for HSIL for those infected with the 12 other high-risk types of HPV with concurrent abnormal TCT results. This study revealed that potential vaginal microbiome biomarkers may relate to HSIL, and can facilitate the cervical cancer screening., Competing Interests: The 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 © 2021 Chao, Wang, Wang, Lang, Tan, Fan and Shi.)

Persistent infection with the human papillomavirus 16 (HPV 16) is the cause of half of all cervical carcinomas (CC) cases. Moreover, mutations in the oncoproteins E6 and E7 are associated with CC development. In this study, E6/E7 variants circulating in southern Mexico and their association with CC and its precursor lesions were evaluated. In total, 190 DNA samples were obtained from scrapes and cervical biopsies of women with HPV 16 out of which 61 are from patients with CC, 6 from patients with high-grade squamous intraepithelial lesions (HSIL), 68 from patients with low-grade squamous intraepithelial lesions (LSIL), and 55 from patients without intraepithelial lesions. For all E7 variants found, the E7-C732/C789/G795 variant (with three silent mutations) was associated with the highest risk of CC (odd ratio (OR) = 3.79, 95% confidence interval (CI) = 1.46-9.85). The analysis of E6/E7 bicistron conferred to AA-a*E7-C732/C789/G795 variants revealed the greatest increased risk of CC (OR = 110, 95% CI = 6.04-2001.3), followed by AA-c*E7-C732/C789/G795 and A176/G350*E7-p. These results highlight the importance of analyzing the combinations of E6/E7 variants in HPV 16 infection and suggest that AA-a*E7-C732/C789/G795, AA-c*E7-C732/C789/G795, and A176/G350*E7-p can be useful markers for predicting CC development.

Aim: The value of top-hat procedure during loop electrosurgical excision procedure (LEEP) for squamous intraepithelial lesions had remained controversial. This study aimed to evaluate whether top-hat specimens positive for cervical intraepithelial neoplasia (CIN) on histopathology can serve as an independent risk factor to predict treatment failure., Methods: We reviewed the medical records of patients who underwent LEEP and top-hat procedures in Peking University First Hospital between 2011 and 2016 and collected their follow-up data until January 2019. We compared the pathological risk factor of treatment failure. Multivariate analysis was carried out to clarify the independent determinant of treatment failure. A Cox model was used to assess the influence of different variables on cumulative treatment failure rates., Results: This study included 295 cases for short-term treatment failure, and among them, 178 cases were used to study the long-term. The presence of CIN in top-hat was relevant to short-term treatment failure (OR = 9.64, 95% CI 2.55-36.4) despite a clear margin. On multivariate analysis, top-hat result (OR = 3.58, 95% CI 1.30-9.89), age ≥ 50 (OR = 10.2, 95%CI 3.64-28.3) and post-treatment HPV 16/18 infection (OR = 2.35, 95%CI 1.19-4.63) were independent risk factors in predicting short-term failure. In the Cox model, these factors were also associated with higher cumulative failure rates., Conclusion: The current study supported the predictive value of top-hat procedure in short-term failure after LEEP. Typically, women with positive top-hat need closer follow-up despite their negative margin status. Older women with positive top-hat findings and HPV 16/18 infections after the treatment suffer a higher risk of short-term failure., (© 2020 Japan Society of Obstetrics and Gynecology.)

Background/aim: To determine the differential protein profiles of cervical cancer cell lines in order to find potential targets that can be used as biomarkers in low-grade squamous intraepithelial lesions (LSIL) diagnosis., Materials and Methods: Proteomic analysis was performed on cervical cancer cell lines by 2D electrophoresis and liquid chromatography-mass spectrometry. Biomarker validation was performed in histological samples by immunofluorescence., Results: Aldo-keto reductase C1 (AKR1C1) and transketolase-like 1 (TKTL1) proteins were selected as biomarkers and their expression was increased in samples with LSIL diagnosis. TKTL1 in combination with AKR1C1 increased sensitivity and specificity to 75% and 66%, respectively, with an area under curve of 0.76 in receiver operating characteristics curve analysis., Conclusion: AKR1C1 and TKTL1 showed potential as biomarkers for diagnosis of LSIL in Mexican women, with similar sensitivity and specificity to the biomarkers used in clinical trials for diagnosis of LSIL., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Introduction: Papanicolaou testing is effective in identifying squamous intraepithelial lesions of the cervix. Endocervical adenocarcinoma (EAC) and adenocarcinoma in situ (AIS) are far less commonly identified. Endocervical curettings (ECCs) are usually obtained after colposcopic biopsy, sample the endocervical canal, and aid in the detection of endocervical glandular lesions. Here, we examine the utility of Papanicolaou testing and endocervical curetting for detecting AIS and EAC., Materials and Methods: Cases from 2007 to 2019 with a histologically confirmed diagnosis of AIS and EAC were identified and the clinical data and diagnostic material, including the cytology and surgical specimens, obtained., Results: A total of 108 cases of AIS and EAC were identified, Papanicolaou tests were performed in 97 of these cases, and ECC in 87. AIS or EAC were detected in 46.4% of Papanicolaou tests; 41.4% of ECC showed AIS or EAC. A total of 92.7% of cases were positive for high-risk human papillomavirus (HPV) and concurrent squamous intraepithelial lesion was present in 53.3% of cases. AIS or EAC were more commonly identified in cases without concurrent squamous intraepithelial lesions., Conclusions: Papanicolaou testing and endocervical curettings have a low detection rate for AIS and EAC. The majority of AIS and EAC cases test positive for high-risk HPV. Papanicolaou test and ECC show different detection rates and are complementary tools in patients with AIS and EAC. In some settings, an ECC can increase the diagnostic sensitivity and specificity of the pathologic diagnosis., (Copyright © 2020 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Aim: The incidence of anal squamous cell carcinoma (SCC) has increased dramatically in the USA. The squamous intraepithelial lesion has been identified as a precursor lesion to SCC, stratifying the abnormality into low grade or high grade. There have been studies on the prevalence of incidentally found SCC in haemorrhoidectomy specimens, but there are no studies to date on the incidence of dysplasia. The purpose of this study was to establish a baseline incidence of dysplasia that provides helpful information for future epidemiological studies., Methods: This is a retrospective review of patients who underwent haemorrhoidectomy from 2005 to 2019. Pathology regarding the type of dysplasia, medications, and diagnoses that may predispose to immunosuppression were collected., Results: In all, 810 patients with a mean age of 51.7 (range 20-91) years underwent haemorrhoidectomy. Eighteen (2.2%) of the patients had abnormal pathology (low-grade squamous intraepithelial lesion, 3; high-grade squamous intraepithelial lesion, 12; SCC, 2; adenocarcinoma, 1). Thirty-seven (4.5%) of the entire cohort had some risk factors for immunosuppression: chronic steroid use (nine), human immunodeficiency virus (HIV) (13), biologic medications (six), transplant recipients (two) and immunocompromising diseases (four). Only 4/18 patients had an immunosuppression risk in that all four of these patients were HIV-positive. Surveillance following excision was undertaken for an average of 6 (range 1-12) months, during which time four patients underwent a repeat biopsy., Discussion: Anal dysplasia found in an otherwise asymptomatic population has a prevalence of 2.2%. This finding supports the routine examination of benign anorectal specimens undergoing microscopic examination. Interestingly, the majority of the patients identified had no immunosuppressant risk factors., (© 2020 The Association of Coloproctology of Great Britain and Ireland.)

Aim: We aimed to determine the biological processes and pathways involved in cervical carcinogenesis associated with high-risk human papillomavirus (HPV) infection., Materials and Methods: Total RNA was extracted from three formalin-fixed paraffin-embedded (FFPE) samples each of normal cervix, HPV-infected low-grade squamous intraepithelial lesion (LSIL), high-grade SIL (HSIL) and squamous cell carcinoma (SCC). Transcriptomic profiling by microarrays was conducted followed by downstream Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses., Results: We examined the difference in GOs enriched for each transition stage from normal cervix to LSIL, HSIL, and SCC, and found 307 genes to be differentially expressed. In the transition from normal cervix to LSIL, the extracellular matrix (ECM) genes were significantly downregulated. The MHC class II genes were significantly upregulated in the LSIL to HSIL transition. In the final transition from HSIL to SCC, the immunoglobulin heavy locus genes were significantly upregulated and the ECM pathway was implicated., Conclusion: Deregulation of the immune-related genes including MHC II and immunoglobulin heavy chain genes were involved in the transitions from LSIL to HSIL and SCC, suggesting immune escape from host anti-tumour response. The extracellular matrix plays an important role during the early and late stages of cervical carcinogenesis., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

It is crucial to classify cervical lesions into high-grade squamous intraepithelial lesions (HSILs) and low-grade SILs (LSILs), as LSILs are conservatively treated by observation, based on an expectation of natural regression, whereas HSILs usually require electrosurgical excision. In the present study, peripheral blood gene expression profiles were analyzed to identify transcriptomic biomarkers distinguishing HSILs from LSILs. A total of 102 blood samples were collected from women with cervical SILs (66 HSIL and 36 LSIL) for microarray hybridization. Candidate gene signatures were identified using AdaBoost algorithms, and a predictive model was constructed using logistic regression to differentiate HSILs from LSILs. To correct for possible bias as a result of the limited sample size and to verify the stability of the predictive model, a two-fold cross validation and null set analysis was conducted over 1,000 iterations. The functions of the transcriptomic biomarkers were then analyzed to elucidate the pathogenesis of cervical SIL. A total of 10 transcriptomic genes ( STMN3, TRPC4AP, DYRK2, AGK, KIAA0319L, GRPEL1, ZFC3H1, LYL1, ITGB1 and ARHGAP18 ) were identified. The predictive model based on the 10-gene panel exhibited well-discriminated power. A cross validation process using known disease status exhibited almost the same performance as that of the predictive model, whereas null-set analysis with randomly reassigned disease status exhibited much lower predictive performance for distinguishing HSILs from LSILs. These biomarkers were involved in the 'Rho GTPase cycle', 'mitochondrial protein import', 'oncogenic MAPK signaling', 'integrin cell surface interaction' and 'signaling by BRAF and RAF fusions'. In conclusion, peripheral blood gene expression analysis is a promising method for distinguishing HSILs from LSILs. The present study proposes 10 candidate genes that could be used in the future as diagnostic biomarkers and potential therapeutic targets for cervical SILs. A simple, non-invasive blood test would be clinically useful in the diagnosis and classification of patients with cervical SILs., (Copyright: © Zou et al.)

Background & Objective: Cervical cancer is the most common cancer in women worldwide with high mortality, necessitating quicker diagnostic methods. We wish to enhance the existing cervical biopsies of Squamous Intraepithelial Lesions (SIL) using p16 and Ki67 as surrogate markers to assess correlation between its positivity and histological grade of the lesion., Methods: Analysis of p16 and Ki67 expression was done on 31 histopathologically diagnosed cases of SILs. Positive expression of p16 was assessed based on a scoring system and compared with histology and cytology. Ki67 expression was studied and the correlation was observed with degree of dysplasia. Twenty cases of chronic cervicitis was assigned to the control group for comparison., Results: Cases of HSIL showed greater expression of p16 as compared to LSIL. Sensitivity of p16 for HSIL was higher than that for LSIL. The specificity for HSIL and LSIL was 100%. Ki67 expression correlated well with the degree and level of dysplasia with a significant P-value of 0.002., Conclusion: p16 and Ki67 positivity of SILs should point towards further evaluation. The expressions of p16 and Ki67 are useful markers for confirmation of SILs and in predicting HPV infection which can be further confirmed by HPV DNA testing.

Background: The first HPV vaccines licensed targeted two HPV types responsible for most cervical cancers. A 9-valent vaccine (9vHPV), targeting 5 additional types, was introduced in 2016 and is currently the only HPV vaccine available in the United States. Previous studies demonstrated high rates of HPV infection in Alaska Native (AN) women. We sought to measure prevalence of high risk HPV types in AN women undergoing colposcopy and to determine those preventable by vaccination., Methods: For this cross-sectional study, we recruited women who were undergoing colposcopy for clinical indications at Alaska Native Medical Center to obtain cervical brush biopsy samples. Specimens were shipped to Atlanta, Georgia for DNA extraction, HPV detection, and typing using L1 PCR with type-specific hybridization to detect 37 HPV types., Results: Four hundred eighty eight specimens from 489 women were tested. At least one HPV type was found in 458 (94%) specimens. Of 458 participants who were HPV positive, 332 (72%) had two or more types. At least one type targeted by 9vHPV was detected in 95% of participants with CIN 3 (21/22), 82% with CIN 2 (37/45), and 65% with CIN 1 (119/184). ( p  < 0.001) HPV 16 or 18 were detected in 77% (17/22) with CIN 3, 53% (24/45) with CIN 2, and 36% (67/184) with CIN 1. ( p  < 0.001)., Conclusions: A substantial proportion of AN women attending colposcopy clinic had evidence of HPV 16/18 infection, as well as other high risk types targeted by 9vHPV. At least one 9vHPV type was detected in 62% of the participants overall, and 95% of participants with CIN3. AN women are expected to benefit from vaccination against HPV 16/18, and will have greater benefit from 9vHPV. Information from this study could be used to develop public health strategies to increase vaccine uptake, or to track HPV genotype prevalence over time., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)

Introduction: Bcl-2-associated athanogene 3 (BAG3) is a protein involved in apoptosis and stress response, which is overexpressed in invasive cervical cancer. However, nothing is known about BAG3 expression in precancerous lesions of the uterine cervix. We aimed to evaluate the expression of BAG3 in cervical intraepithelial neoplasia/squamous intraepithelial lesions (CIN/SIL)., Material and Methods: Forty patients (16 CIN1/L-SIL, 11 CIN2/H-SIL and 13 CIN3/H-SIL) were assessed by immunohistochemistry for BAG3. The intensity of BAG3 expression was categorized as null, minimal, weak, moderate or strong. The association of BAG2 intensity of expression with the grade of dysplasia was assessed using Chi-square test (significant P value <0.05)., Results: In all normal controls, BAG3 expression was negative. In L-SIL specimens, BAG3 expression was confined to the basal third of the epithelium, with an intensity minimal in nine cases (56.3%), weak in six (37.5%) and strong in one (6.3%). In H-SIL specimens, BAG3 expression involved also the two upper thirds of the epithelium, with an intensity moderate in 13 cases (54.2%; 8 CIN2 and 5 CIN3) and strong in 11 cases (45.8%; 3 CIN2 and 8 CIN3). The distribution of BAG3 expression correlated perfectly with the grade of dysplasia (P = 0.0); a moderate/strong expression of BAG3 was significantly associated with H-SIL (P < 0.0001), with no significant difference between CIN2 and CIN3 (P = 0.1228)., Conclusions: In CIN/SIL, both distribution and intensity of BAG3 expression correlate directly with the grade of dysplasia, supporting the involvement of BAG3 in all phases of cervical carcinogenesis and its possible diagnostic and prognostic role in cervical premalignant lesions., (© 2019 Nordic Federation of Societies of Obstetrics and Gynecology.)

Objective: To evaluate if the intraoperative human papillomavirus (IOP-HPV) test has the same prognostic value as the HPV test performed at 6 months after treatment of high-grade squamous intraepithelial lesion (HSIL) to predict treatment failure., Design: Prospective cohort study., Setting: Barcelona, Spain., Population: A cohort of 216 women diagnosed with HSIL and treated with loop electrosurgical excision procedure (LEEP)., Methods: After LEEP, an HPV test was performed using the Hybrid Capture 2 system. If this was positive, genotyping was performed with the CLART HPV2 technique. The IOP-HPV test was compared with HPV test at 6 months and with surgical margins., Main Outcome Measure: Treatment failure., Results: Recurrence rate of HSIL was 6%. There was a strong association between a positive IOP-HPV test, a positive 6-month HPV test, positive HPV 16 genotype, positive surgical margins and HSIL recurrence. Sensitivity, specificity, and positive and negative predictive values of the IOP-HPV test were 85.7, 80.8,24.0 and 98.8% and of the HPV test at 6 months were 76.9, 75.8, 17.2 and 98.0%., Conclusion: Intraoperative HPV test accurately predicts treatment failure in women with cervical intraepithelial neoplasia grade 2/3. This new approach may allow early identification of patients with recurrent disease, which will not delay the treatment. Genotyping could be useful in detecting high-risk patients., Tweetable Abstract: IOP-HPV test accurately predicts treatment failure in women with CIN 2/3., (© 2019 Royal College of Obstetricians and Gynaecologists.)

Purpose: FOXP3 is a marker of the T regulatory (Treg) cell subset and drives its function and homeostasis. Its expression maintains the host immunosuppressive state that favors persistence of human papillomavirus (HPV) infection and squamous intraepithelial lesion (SIL) appearance. The present study evaluated the effects of the rs3761548 and rs2232365 intronic single-nucleotide variants (SNVs) and their haplotypes on HPV infection and SIL diagnosis in HPV-infected and -uninfected women., Methods: HPV DNA-based detection in cervical specimens was performed by PCR. FOXP3 variants were genotyped by PCR-restriction fragment length polymorphism and haplotype recombination sites were inferred for 208 HPV-infected and 218 HPV-uninfected women diagnosed or not with low- or high-grade intraepithelial lesions of cervix. Case-control analyses were carried out by logistic regression adjusted for several socio-demographic, sexual lifestyle, and clinical data., Results: The homozygous genotype of the rs3761548 variants (A/A) (related to decreased FOXP3 expression) may exert a protective role against HPV infection in women (OR Aj : 0.60; 95% CI 0.36-0.99; p = 0.049) and was an independent predictor of protection against HSIL development (OR Adj : 0.28; 95% CI 0.11-0.68; p = 0.006). In addition, the homozygous genotype (G/G) of the rs2232365 variants (related to increased FOXP3 expression) was independently associated with the HPV infection (OR Adj : 2.10; 95% CI 1.06-4.15; p = 0.033). Haplotype analysis revealed no significant associations in our study., Conclusions: Our results reveal the significant and independent associations between FOXP3 genetic variants and susceptibility to HPV infection and SIL diagnosis and their role as biomarkers of HPV infection and cervical lesion management.

Objectives: Human papillomavirus (HPV) is known to be associated with squamous intraepithelial lesions (SILs). However, there is limited and conflicting literature on the relationship between bacterial vaginosis (BV) and SIL. The aim of this study is to determine the prevalence of BV and evaluate the association between BV and SIL., Methods: A retrospective study was performed on 10,546 cases between 2012 and 2017. HPV results were available in 7,081 cases., Results: BV was present in 17.6% of cases. There was significant association between BV, positive HPV infection, and high-grade SIL. BV patients with negative HPV infection showed more squamous abnormalities than BV-negative HPV-negative patients., Conclusions: We found there is a significant association between BV and SIL. BV is more common among patients with HPV infection and is independently associated with squamous abnormalities in cervical smears and surgical follow-up., (© American Society for Clinical Pathology, 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Even though cervico-vaginal smears have been used as a primary screening test for cervical carcinoma, the diagnostic accuracy has been controversial. The present study aimed to evaluate the diagnostic accuracy of cytology for squamous intraepithelial lesion (SIL) and squamous cell carcinoma (SqCC) of the uterine cervix through a diagnostic test accuracy (DTA) review., Methods: A DTA review was performed using 38 eligible studies that showed concordance between cytology and histology. In the DTA review, sensitivity, specificity, diagnostic odds ratio (OR), and the area under the curve (AUC) on the summary receiver operating characteristic (SROC) curve were calculated., Results: In the comparison between abnormal cytology and histology, the pooled sensitivity and specificity were 93.9% (95% confidence interval [CI], 93.7%-94.1%) and 77.6% (95% CI, 77.4-77.8%), respectively. The diagnostic OR and AUC on the SROC curve were 8.90 (95% CI, 5.57-14.23) and 0.8148, respectively. High-grade squamous intraepithelial lesion (HSIL) cytology had a higher sensitivity (97.6%; 95% CI, 94.7%-97.8%) for predicting HSIL or worse histology. In the comparison between SqCC identified on cytology and on histological analysis, the pooled sensitivity and specificity, diagnostic OR, and AUC were 92.7% (95% CI, 87.3%-96.3%), 87.5% (95% CI, 87.2%-87.8%), 865.81 (95% CI, 68.61-10,925.12), and 0.9855, respectively. Geographic locations with well-organized screening programs had higher sensitivity than areas with insufficient screening programs., Conclusion: These results indicate that cytology had a higher sensitivity and specificity for detecting SIL and SqCC of the uterine cervix during primary screening., Competing Interests: Disclosure: The authors have no potential conflicts of interest to disclose.

Aim: To investigate the features of skip lesions and evaluate value of top-hat procedure in management of squamous intraepithelial lesion., Methods: We reviewed the records of patients who underwent loop electrosurgical excision procedure (LEEP) in Peking University First Hospital between 2011 and 2016. Patients were confirmed to have CIN1-3. The term 'skip lesion' refers to lesion lying deep in cervical canal discontiguous with other lesions in transformation zone and was confirmed by top-hat. We compared their lesion grade in patients with or without skip lesion using logistic regression. We further reviewed patients who underwent subsequent hysterectomy within 6 months following LEEP and evaluated if top-hat procedure led to less residual lesions or was able to predict residual lesions., Results: A total of 2260 patients were included and 595 underwent top-hat procedure. Thirty-nine out of 595 patients had skip lesions (6.5%), among whom two patients had CIN1 (5.1%), eight had CIN2 (20.5%) and 29 had CIN3 (74.4%). Logistical regression showed CIN3 was associated with higher risk of skip lesions compared to CIN1 (OR = 4.433, 95%CI: 1.036-18.964), while CIN2 was not (OR = 1.762, 95%CI: 0.366-8.471). Sixty-two patients underwent hysterectomy within 6 months following LEEP (CIN1-3), 24 underwent top-hat. Analysis revealed top-hat procedure did not result in less residual lesions. Colposcopy impression or prior HPV test was unable to predict skip lesions., Conclusion: About 9.4% patients with CIN3 had skip lesions in the study, which is associated with elevated risk for residual lesion. Top-hat procedure is able to detect skip lesions, but should not be performed on routinely because its prognostic value is not proved., (© 2018 Japan Society of Obstetrics and Gynecology.)

Background: The 2014 Bethesda System for Reporting Cervical Cytology classifies squamous intraepithelial lesions (SILs) of cervix into two main categories: low-grade SIL (LSIL) and high-grade SIL (HSIL). In some clinical practices, the LSIL cannot rule out high-grade lesion (LROH) interpretive category is used in cases with LSIL and findings that may raise the possibility of HSIL. Our purpose is to assess follow-up histopathology and high-risk human papillomavirus (hrHPV) results in patients with LROH, in comparison with LSIL, atypical squamous cells, cannot rule out HSIL (ASC-H), and HSIL in our institution., Design: Cervical Papanicolaou tests with LROH, LSIL, ASC-H and HSIL interpretation, surgical follow-up, and hrHPV status were retrieved from the computer database from May 2014 to December 2016., Results: Of 109 963 total Papanicolaou tests, LROH comprised 0.3%, LSIL 3.1%, ASC-H 0.2% and HSIL 0.4%. Only 3272 cases with surgical diagnoses were included in the study. The most common histological outcome for ASC-H was cervical intraepithelial neoplasia (CIN)2/3 (32.6%); LSIL was CIN 1 (45.7%); LROH was CIN 1 (46.7%) and HSIL was CIN 2/3 (64.4%). For LROH and LSIL, 31.1% and 7.5% respectively, had CIN 2/3. Approximately 79% of cases were hrHPV positive. Of LROH cases with surgical follow-up, 86.9% tested hrHPV positive, accounting for the second most common positive group after HSIL (92.6%)., Conclusion: In our study cohort, LROH interpretation is associated with a higher number of CIN 2 or higher lesions on follow-up compared to patients with LSIL (P < 0.0001), and is associated with a significant percentage of positive other hrHPV, supporting LROH as a useful diagnostic category that triggers appropriate follow-up in affected women., (© 2018 John Wiley & Sons Ltd.)

Objectives: The paper assess the relevance of HR HPV E6/E7 mRNA test in women with abnormal Pap results., Material and Methods: Between 2013-2014, 125 women were subjects to the enhanced diagnostics due to abnormal Pap results. According to The Bethesda system, if ASC-US, AGC, LSIL, ASC-H, HSIL or cancer cells were present, the result was abnormal. The patients underwent the enhanced diagnostics which included the following procedures: Pap smear collection for molecular assessment of HR HPV E6/E7 mRNA test, the colposcopic examination and biopsy of clinically suspicious areas., Results: High-grade squamous intraepithelial lesions constituted the most frequent cervical pathology in women with abnormal Pap test results, as well as with the positive results of HR HPV E6/E7 mRNA test. Test sensitivity in patients with the histopathological diagnosis of high-grade squamous intraepithelial lesion was estimated at 86.1%., Conclusions: HR HPV E6/E7 mRNA test identifying neoplastic lesions and cervical cancer is characterised by a high relevance which is reflected by means of sensitivity and specificity. In fact, test sensitivity and specificity increased with the age in the group of patients up to 50 years old.

Cervical carcinoma is one of the most common and dreaded diseases of women, and in India, it accounts for 16 per cent of total cervical cancer cases occurring globally. The situation is more alarming in the rural areas where the majority of women are illiterate and ignorant about the hazards of cervical cancer. Different screening strategies such as rural cancer registries and camp approach for cancer detection have been found useful in minimizing the problem of cervical cancer in the villages. Various screening techniques such as visual inspection with acetic acid, visual inspection with Lugol's iodine, visual inspection with magnification devices-magnavisualizer, Pap smear and HPV-DNA testing have been suggested and tried under low-resource settings of our country, and cervical cytology screening has been found effective in reducing incidence of the disease. In the present review, feasibility of different screening methods has been assessed to find out the most suitable mode applicable at the rural level. Single lifetime screening particularly of high-risk women along with analysis of cost-effective tumour markers such as Argyrophilic nucleolar organizer regions (AgNOR) counts to discriminate high-risk dysplasia cases appears to be an appropriate approach in fighting against cervical cancer., Competing Interests: None

Purpose: To determine whether quadrivalent HPV vaccination is effective in reducing recurrent disease in women with a previous history of HPV disease., Methods: All women under 45 years of age treated for HPV-linked disease and with negative HPV test, cytology and colposcopy 3 months after treatment were enrolled. Women were randomly assigned into two groups: a group that received HPV vaccine post treatment and a group that was only submitted to follow-up. Follow-up was performed every 6 months for a duration of at least 3 years. Kaplan-Meier curve was used to estimate the overall disease-free survival during the follow-up period. Statistical analysis was performed by Fisher's exact test., Results: From November 2013 to October 2014, we enrolled a total of 178 women at Careggi University Hospital in Florence and at Azienda USL in Massa Carrara. 12 out of 89 patients in the non-vaccination group recurred (13.5%), while 3 out of 89 patients in the vaccination group recurred (3.4%). The Kaplan-Meier curves showed a statistically difference in the log rank test (p = 0.0147) for the overall disease-free survival in the study groups during follow-up. The rate of recurrence was significantly higher in the non-vaccination group, with a p = 0.0279 by Fisher exact test., Conclusion: The introduction of anti-HPV vaccination during the follow-up post treatment for HPV-linked disease is recommended to reduce the risk of recurrence. The clinical implication of this could be very important to influence post-treatment management of HPV disease.

Background: Benign, premalignant and malignant changes in the anogenital region, as in the oropharynx are often affected by a persistent HPV infection. Since a causal therapy isn't possible, the focus is on early diagnosis of dysplasia. Better knowledge of the human papilloma virus led to the development of the HPV vaccine and now primary prevention of cancer is possible. These findings will also influence the German cervical cancer screening., Objectives: This article illustrates prevalence, significance, diagnostics, treatment and prevention of HPV infection and HPV-associated diseases in women., Material and Methods: A literature research under pubmed.de has been carried out. In addition up-to-date guidelines and internet-based sources were considered., Results: Persistent infection can lead to dysplasia and carcinoma of the cervix, vagina and vulva, the anus and the oropharynx. In future an additional HPV testing is planned to be integrated in the German screening for cervical cancer for women above 35 years. Management of dysplasia is operative or topical. Accordingly, a primary prevention through vaccination is even more important. The German Standing Vaccination Committee recommends the vaccination for girls and boys between 9 to 14 years., Conclusion: HPV vaccination is a secure and efficient procedure to prevent cancer. In the following years it is of great importance to improve acceptance and vaccination rates.

Background: In the life of a woman, after 40 years of age, onset of menopause occurs during which hormonal imbalances take place. The present study is aimed at finding out cytopathological changes in the cervical epithelium associated with this hormonal disturbance., Materials and Methods: Cervical cancer screening program is in progress under auspices of Era's Lucknow Medical College and Hospital, Lucknow, since May 2013, in the villages of Lucknow West through camp approach. Till September 2017, 140 camps have been organized and 2440 women attending the camp have been cytologically examined. Out of these, 1534 women were perimenopausal, 165 premenopausal, and 441 postmenopausal. The cytopathological changes have been studied in these three categories of women in relation to different predisposing factors to the cervical carcinogenesis., Results: The squamous intraepithelial lesion (SIL) rate was higher with onset of menopause in the premenopausal women. The SIL rate was higher with nulliparity in these women as well as in the postmenopausal women and also with different gynecological symptoms and clinical lesions of the cervix. The SIL changes associated with HPV and HSV were also higher in them., Conclusion: A high SIL rate found with onset of menopause may be the outcome of gradual estrogen withdrawal in the premenopausal women. Hence, cytological evaluation is mandatory in women between 41 and 45 years of age to rule out any occurrence of cervical cytopathology., Competing Interests: There are no conflicts of interest.