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Background: Valid diagnostic tests for human papillomavirus (HPV) detection are crucial to identify individuals at high risk of cervical cancer. We assessed and compared the validity of Mehrviru HPV genotyping and Sacace (HPV Genotypes 14 Real-TM Quant) for molecular detection of 14 high-risk human papillomaviruses., Methods: We used three HPV test results to identify HPV-positive individuals (14 high-risk genotypes) in a specialist gynecology clinic. The HPV test results were collected using Mehrviru ® , Sacace ® , and a third kit from the clinical diagnostic laboratory. We used Latent class analysis to determine the actual status of HPV infection in study participants. The sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios, Youden, and area under the ROC curve indices of each diagnostic kit and their 95% confidence intervals were calculated. The agreement between the Mehrviru and Sacace kits was determined using the Kappa statistic., Results: We examined 117 women at high risk of HPV infection. The mean age (SD) was 37.2 (9.1). According to LCA, 28.6% of participants had an HPV infection. The sensitivity and specificity (95% CI) of the Mehrviru were 90.8% (73.7-97.2%) and 90.9% (82.1-95.6%), and corresponding figures for Sacace were 92.0% (72.3-98.1%) and 97.4% (90.2-99.3%). The kappa index between the Mehrviru and Sacace kits was 69.7% (55.6-83.9%). The area under the ROC curve for Mehrviru and Sacace test were 91.4% (85.7-97.1%) and 94.4% (89.3-99.5%)., Conclusions: There is an excellent agreement between Mehrviru and Sacace test results, and the diagnostic accuracy indices were similar., Competing Interests: Declarations Ethics approval and consent to participate This study was approved by Iran University of Medical Sciences’ Ethics Committee, reference: IR.IUMS.REC.1400.924, and written informed consent was obtained from all the participants. Consent for publication Not applicable. Competing interests MS is the technical manager and DH is the head of department of Pathology and Molecular Medicine at Mehr Clinical Diagnostic Laboratory. MSD advises MCDL on research project. HN and FRT declare no conflict of interest., (© 2024. The Author(s).)

Cervical cancer is a preventable disease. Nevertheless, stagnation has been seen in incidence rates also in countries with well-functioning healthcare. On this basis, we investigated associations between control interventions and changes in cervical cancer incidence in Denmark from 2009 to 2022. Data on human papillomavirus (HPV)-vaccination were retrieved from Staten's Serum Institute; on screening recommendations from Danish Health Authority, on screening performance from Danish Quality Database for Cervical Screening; and on cervical cancer incidence from Nordcan and Danish Cancer Register. We reported coverage with HPV vaccination (1+ dose); coverage with cervical cell samples; number of women with primary HPV tests; proportion of non-normal cell samples without timely follow-up; number of conizations; and cervical cancer incidence rates. In 2022, all women aged ≤29 had been offered childhood HPV vaccination with coverage of 80%-90%. By 2020-2022, the cervical cancer incidence rate in women aged 20-29 was 3 per 100,000; at level of disease elimination. In 2017, women aged 70+ were offered a one-time HPV screening, and by 2020-2022, the old-age peak in cervical cancer incidence had largely disappeared. From 2009 to 2022, proportion of non-normal cell samples without timely follow-up decreased from 20% to 10%, and conventional cytology was largely replaced by SurePath liquid-based cytology; these factors could explain the steady decrease in cervical cancer incidence rate. Implementation of primary HPV screening in women aged 30-59 in 2021 was reflected in a, probably temporary, increase in the 2022 cervical cancer incidence rate. In conclusion, combined interventions with childhood HPV vaccination; one-time HPV screening of elderly women; and better management of screening broke previous stagnation in cervical cancer incidence rate., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Human papillomavirus 16 (HPV16) infection is the leading cause of cervical cancer. The current mainstream method for detecting HPV16 is quantitative real-time PCR (qPCR). However, due to its time-consuming nature and reliance on expensive qPCR instruments, there is growing interest in more convenient, rapid and private approaches such as recombinase polymerase amplification (RPA). In this study, we innovated an effective method for HPV16 detection by integrating a RPA system with lateral flow strip (LFS) detection. Primers with optimal efficiency and specificity were designed, and false positive signals caused by dimers were eliminated by reducing the probe concentration. The RPA-LFS method demonstrates high sensitivity and specificity, capable of detecting 230 copies per reaction of HPV16 within 25 min without cross-reactivity to other subtypes. It exhibits good tolerance, remaining unaffected by 1.0% miconazole, 0.5% tioconazole and 1.0% hemoglobin. The results of clinical samples detected by this method were consistent with those of qPCR. The method provides a practical reference for HPV16 diagnosis and can be valuable in home and resource-limited settings, contributing to the reduction of cervical cancer incidence.

High-risk human papillomavirus infection (HR-HPV) is necessary but not the only factor needed to develop cervical cancer. It is essential to estimate cervical cancer development risk in the population of high-risk HPV-positive women and to avoid unnecessary examinations and treatment in low-risk individuals. The study aimed to identify associations between different personal factors, vaginal microflora, sexually transmitted, high-risk HPV infection, and various degrees of cervical precancerous lesions. A study was performed in 2016-2020. The study group consisted of 112 patients with abnormal cervical cytology results referred for colposcopic examination. 120 women who came for a routine gynecological check-up were included in the control group. Material from the cervix and upper vaginal fornix was taken for pH measurement, wet mount microscopy, testing the six most common high-risk HPV DNA types (16/18, 31, 33, 45, 58), HPV E6/E7 mRNA, and 7 genital infections-C. trachomatis, N. gonorrhea, T. vaginalis, M. hominis, M. genitalium, U. urealyticum, U. parvum. Results showed that women with all grades of cervical intraepithelial neoplasia (CIN) more often were smokers, had increased vaginal pH levels, and had positive HR-HPV DNA and HR HPV E6/E7 mRNA expression. Abnormal vaginal microflora, especially types associated with aerobic vaginitis, and M. hominis were significantly more often found in women with CIN2+. The presence of C.trachomatis, U. parvum, and U.urealyticum did not differ between the groups. The most important factors independently associated with CIN2+ were positive high-risk HPV E6/E7 mRNA expression (OR 59.4, 95% CI 14.84-237.51), and positive high-risk HPV DNA (OR 3.9, 95% CI 1.16-13.23). Higher education level was associated with reduced risk of CIN2+ (OR 0.2, 95% CI 0.07-0.71). In conclusion, this study reports HR-HPV DNA of the most common six types and E6/E7 mRNA positivity as the most significant factors associated with CIN2+ lesions and higher education related to lower risk of high-grade cervical lesions., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Plisko et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Atypical squamous cells of undetermined significance (ASC-US) often present diagnostic challenges with cytology-based results, leading to potential underdiagnosis or overdiagnosis. An effective triage method is essential for managing these cases to reduce unnecessary referrals and treatment., Methods: A total of 322 women diagnosed with ASC-US were tested for HPV-DNA and the PAX1 and JAM3 methylation (PAX1 m /JAM3 m ) test in the study., Results: Methylation levels of PAX1 and JAM3 were significantly elevated in cervical lesions classified as CIN2 or more severe lesions (CIN2+). The methylation assay demonstrated a sensitivity of 83.8% and a specificity of 95.8%, outperforming HPV-DNA testing in differentiating high-grade cervical lesions among women with ASC-US. Moreover, PAX1 m /JAM3 m testing significantly reduced the colposcopy referral rate for further diagnostic procedures in high-risk HPV-positive women by 79.5%., Conclusions: PAX1 m /JAM3 m testing shows promise as a reliable supplemental method to HPV-DNA testing for the triage of women with cytologic ASC-US. In addition, the molecular triage based on the CISCER assay or single PAX1 or JAM3 methylation, had better effects in the women with non-HPV16/18 group. This approach could potentially minimize overtreatment and unnecessary referrals in clinical practice, enhancing patient management and resource utilization., Competing Interests: Declarations Ethical approval The name of the Approval Committee or the Internal Review Board (IRB). This research has been approved by the Ethics Committee of Zhejiang Provincial People’s Hospital. Human Ethics and Consent to participate declarations All participants have provided written informed consents according to the Declaration of Helsinki, and which have been approved by the Ethics Committee of Zhejiang Provincial People’s Hospital (No.2021SJ020). Consent for publication Not applicable. Clinical trial number Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

We aimed to evaluate the diagnostic value of TruScreen, a real-time diagnostic technology, for cervical lesions in patients with different transformation zone (TZ) types. A total of 1908 women aged 34.0 ± 7.3 years who have received cytology, human papillomavirus (HPV) testing, TruScreen, and colposcopy were recruited. The clinical performances of these tests were evaluated for their detection of high-grade squamous intraepithelial lesion (HSIL), adenocarcinoma in situ (AIS), or more severe lesions in patients with different TZ types. For the detection of HSIL, AIS, or more severe lesions, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of TruScreen were 65.08%, 64.76%,11.55%, and 96.33%, respectively, which were similar to cytology (all P values > 0.05). For the detection of HSIL + in patients with type 3 TZ, the sensitivity, specificity, PPV, and NPV of TruScreen were 72.29%, 67.59%, 13.86%, and 97.13%, respectively, which were significantly higher than the sensitivity (51.16%, P = 0.029), specificity (59.59%, P = 0.001), PPV (7.94%, P = 0.016), and NPV (94.71%, P = 0.049) in type 1 and type 2 TZs. TruScreen has detection accuracy comparable to cytology and performs even better in patients with type 3 TZ., (© 2024. The Author(s).)

Background: The World Health Organization has set ambitious goals to eliminate cervical cancer, necessitating evidence on increasing coverage and access to screening and treatment in high-burden areas. We implemented a pilot program to assess the feasibility of obtaining self-collected specimens for high-risk human papillomavirus (hr-HPV) testing in Nzulezo stilt village, a hard-to-reach community in Ghana, and inviting only hr-HPV-positive women to a central location for colposcopy and possible treatment. Subsequently, this study aimed to investigate the prevalence of hr-HPV infection and cervical lesions among the women and to explore factors potentially associated with hr-HPV infection among them., Methods: This pilot community-based cross-sectional study utilized data from screening sessions held from 2 to 20 November 2021 with specimens collected by participants using Evalyn brushes. HPV DNA testing was performed using the Sansure MA-6000 platform, while visual inspection utilized the Enhanced Visual Assessment (EVA) mobile colposcope. Univariate and multivariable nominal logistic regression was employed to explore factors associated with hr-HPV positivity., Results: Among 100 women screened (mean age, 43.6 ± 14.5 years), the overall hr-HPV prevalence rate was 39.0% (95% CI, 29.4-49.3). The prevalence rates of hr-HPV genotypes were stratified as follows: HPV16-8.0% (95% CI, 3.5-15.2), HPV18-5.0% (95% CI, 1.6-11.2), and other genotype(s) - 31.0% (95% CI, 22.1-41.0). Single-genotype infections with HPV16 and HPV18 were found in 4.0% (95% CI, 1.1-9.9) and 3.0% (95% CI, 0.6-8.5) of women, respectively. Mixed infections were observed in 1.0% (95% CI, 0.0-5.4) for HPV16 + 18, 3.0% (95% CI, 0.6-8.5) for HPV16 + other type(s), and 1.0% (95% CI, 0.0-5.4) for HPV18 + other type(s). The prevalence of cervical lesions among hr-HPV-positive women screened via colposcopy was 11.4% (95% CI, 3.2-26.7). In the multivariable model, reliance on other sources for medical bill payment was associated with hr-HPV infection (aOR, 0.20; 95% CI, 0.04-0.93), whereas age was not (aOR, 1.02; 95% CI, 0.99-1.05)., Conclusions: A high hr-HPV infection prevalence was recorded among the women. Utilizing technologies such as self-sampling, HPV DNA testing, and mobile colposcopy enables screening and treatment in remote and hard-to-reach communities where access to cervical cancer screening and treatment would otherwise be limited. Further research is warranted to assess the value and scalability of this approach in similar remote areas and its potential implementation in future programs., (© 2024. The Author(s).)

Cervical cancer, whose well-recognized etiological agent is the Human Papillomavirus (HPV), is responsible for approximately 300,000 deaths worldwide, 80% of cases occurring in developing countries. In Brazil, 17,010 cases were expected, with 2,550 cases in São Paulo State, in 2023. The Papanicolaou test is the diagnostic method for the detection of precancerous lesions of the cervix, and HPV vaccination is now available for prevention., Materials and Methods: This is a descriptive and exploratory, retrospective investigation, carried out through analysis of data obtained from Brazilian Information Technology (DATASUS) of the Brazilian Federal Government: Cancer Information System (SISCAN), Brazilian National Immunization Program (PNI) and Mortality Information System (SIM). Electronic Library and data made available by the Government of the State of São Paulo., Results: The number of women in São Paulo State who underwent cytological examinations and histological tests for cervical cancer decreased between the Years 2013 and 2022., Conclusion: The continuous increase in cervical cancer over the study period was probably due to the lack of adherence to the primary and secondary prevention opportunities offered by the Public Health Authorities., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)

Prophylactic human papillomavirus (HPV) vaccines against cervical cancer were successfully developed; however, challenges such as high cost and low compliance still remain to be overcome. In addition, because many HPV types can cause cervical cancer, antigens of multiple HPV types are needed to achieve broad protection. In this study, a bivalent single-injection HPV vaccine was designed in which virus-like particles (VLPs) of HPV 16 L1 and HPV 18 L1 were used as antigens. A recently developed drug carrier that uses tannic acid/polyethylene glycol films as the erodible layer was employed to accomplish multiple pulsatile releases of the antigens. Monovalent single-injection vaccines for HPV 16 and HPV 18 were first designed. A bivalent single-injection vaccine was then obtained by simply mixing the two monovalent vaccines. The bivalent vaccine provided protection against both HPV types. More importantly, it elicited both humoral and cellular immune responses as potent as those elicited by the corresponding multiple dose vaccine because of their similar release profile of antigens. Cross-reactivity was observed between HPV 16 and 18 in terms of cellular immune responses, while no cross-reactivity was found in terms of humoral immune responses. Note that other multivalent single-injection vaccines could be designed in the same way. These vaccines are expected to help prevent cervical cancer because of their broad protection, enhanced compliance and lowered vaccination cost.

Background: Cervical cancer is the 2nd most common female cancer among Sri Lankan females and is almost associated with sexually transmitted cervicovaginal human papillomavirus (HPV) infection. The study objectives were to determine the prevalence of vaginal and cervical HPV infection among 35year old ever-married women and assess the validity of primary healthcare provider-collected vaginal HPV/DNA specimens as a cervical cancer screening tool to improve the coverage of the programme., Method: A descriptive cross-sectional study was carried out from the 1st of September 2018 to the 31st of January 2019. Ever-married women 35 years of age in Kalutara district were the study population. Two women from each Public Health Midwife area (n = 413) were selected randomly from the relevant area eligible families register/s. HPV/DNA cervical specimen and vaginal specimen collection (n = 621) were carried out. Specimens were screened by the Cobas 4800 HPV/DNA automated Polymerase Chain Reaction (PCR) machine. Participants' profiles were recorded by the research assistants using an interviewer-administered questionnaire., Results: The overall prevalence of vaginal and cervical HPV infection was 7.08% (95% CI; 5.2-9.4%) and 6.12% (95% CI; 4.26-8.3%) respectively. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), diagnostic accuracy, and the kappa coefficient of the vaginal HPV/DNA screening method vs. cervical HPV/DNA screening method were 100%, 98.9%, 86.4%, 100%, 99% and 0.92 respectively., Conclusions: Vaginal HPV/DNA specimen screening method can be used as a cervical cancer screening tool due to its high validity. Pilots of the feasibility should be set up before the regional or national rollout of vaginal sampling strategies., (© 2024. The Author(s).)

In October 2023, Nigeria integrated the single-dose human papillomavirus (HPV) vaccine into its routine immunization program, aiming to protect 7.7 million girls aged 9 to 14 years. This milestone in the fight against HPV-related cancers, especially cervical cancer, faces significant challenges due to high vaccine rejection rates driven by misinformation and cultural barriers. Despite the vaccine's proven safety and efficacy, uptake remains low. This communication highlights the urgent need for a comprehensive public health education campaign to address these barriers. Proposed strategies include leveraging digital health technologies, integrating HPV education into school curricula, training community health workers, engaging religious and cultural leaders, and launching media campaigns featuring personal narratives. Implementing these evidence-based interventions is crucial for dispelling myths, misconceptions, and skepticism surrounding HPV vaccines. This will enhance acceptance and uptake, ultimately reducing cervical cancer mortality in Nigeria., (©2024 American Association for Cancer Research.)

Background: Primary screening for high-risk human papillomavirus (hrHPV) with cytological triage for women with non-16/18 hrHPV-positive status has become popular in China. However, cytology relies on the subjective judgment of pathologists, leading to inconsistent clinical performance., Methods: A total of 657 hrHPV-positive women aged 25-64 years were enrolled in this cross-sectional study. All participants underwent colposcopic biopsy after cytology triage, with cytology residual specimens undergoing DNA methylation testing. CIN2+ and CIN3+ sensitivity and specificity were compared between the different triage strategies (n=487): PAX1 methylation (PAX1 m ) , Glycophorin C methylation (GYPC m ), cytology, and combinations between them or with HPV16/18., Results: The area under the receiver operating characteristic curves (AUCs) for PAX1 m and GYPC m in detecting CIN2 or worse (CIN2+) were 0.867 (95% confidence interval [CI]: 0.796-0.937) and 0.873 (95% CI: 0.808-0.938), respectively. The sensitivities of PAX1 m and GYPC m were consistent with those of cytology for both CIN2+ and CIN3+ detection. The relative specificities of PAX1 m and GYPC m for CIN2+ detection compared to cytology were 2.83 (95% CI: 2.33-2.45) and 3.09 (95% CI: 2.40-3.98), respectively. The relative specificities of combining HPV 16/18 with PAX1 m and GYPC m for CIN2+ detection compared to cytology were 3.38 (95% CI: 2.96-3.86) and 3.67 (95% CI: 3.15-4.27), respectively. Compared to low levels of DNA methylation, high levels of PAX1 m and GYPC m resulted in odd ratios (ORs) of 57.66 (95% CI: 13.57-409.12, p < 0.001) and 23.87 (95% CI: 6.49-115.42, p < 0.001) for CIN3+, adjusted for HPV 16/18 and cytology results., Conclusions: PAX1 m and GYPC m demonstrated superior ability to identify cervical precancerous lesions and cervical cancer, with AUC values exceeding 0.85. For detecting CIN2+/CIN3+ in women with hrHPV-positive status, DNA methylation (combined with HPV 16/18) showed higher specificity than cytology (combined with HPV 16/18) and is a potential molecular biomarker for detecting cervical (pre)cancer., (© 2024. The Author(s).)

Background: Most women who are high-risk human papilloma virus (hrHPV) positive in a cervical cancer screening test will spontaneously heal from their infection. Visual inspection with acetic acid (VIA) is recommended by the World Health Organization as a triage test for cervical screening, however its accuracy as a triage test has been questioned. In this study, we aimed to examine the sensitivity and specificity of VIA with and without Lugol's iodine as a triage test to detect cervical intraepithelial neoplasia (CIN2+) among women who tested positive for hrHPV after self-sampling., Method: This two-armed randomized controlled trial (RCT) took place in Adama, Ethiopia. The women who tested positive for vaginal hrHPV (Anyplex ΙΙ, Seegene) after self-sampling were randomized to VIA with or without iodine and appointed to a midwife-led clinic. The result of the triage test was categorized as positive, negative, suspicion of cancer or inconclusive, and treated accordingly. Cervical biopsies were collected from women who were hrHPV positive to serve as a gold standard., Results: 22.4% (197/878) of women tested hrHPV positive. Sensitivity and specificity for VIA to detect CIN2+was 25.0% (95% CI 0.6 to 80.0) and 82.7% (95% CI 69.7 to 91.8), respectively. For VIA with iodine, the sensitivity was 50.0% (95% CI 0.7 to 93.2) and the specificity 86.3% (95% CI 71.4 to 93.0). The difference between the two methods was not statistically significant, p=0.5. The odds of detecting CIN2+ was 5.4 times higher if positive for VIA with iodine compared with a negative result. For VIA without iodine, the odds of detecting CIN2+ was 1.6 compared with a negative result. The odds of detecting CIN2+ was 6.4 times higher if the women were HIV positive than for those who were HIV negative., Conclusion: VIA with iodine improved detection of CIN2+ in women who were hrHPV DNA positive but was not significantly better than VIA alone., Trial Registration Number: NCT05125380., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2024. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Vaginal dysbiosis is implicated in persistent human papillomavirus (HPV) infection and cervical cancer. Yet, there is a paucity of data on the vaginal microbiome in Native American communities. Here, we aimed to elucidate the relationships between microbiome, HPV, sociodemographic, and behavioral risk factors to better understand an increased cervical cancer risk in Native American women. In this pilot study, we recruited 31 participants (16 Native American and 15 non-Native women) in Northern Arizona and examined vaginal microbiota composition, HPV status, and immune mediators. We also assessed individuals' sociodemographic information and physical, mental, sexual, and reproductive health. Overall, microbiota profiles were dominated by common Lactobacillus species (associated with vaginal health) or a mixture of bacterial vaginosis-associated bacteria. Only 44% of Native women exhibited Lactobacillus dominance, compared with 58% of non-Native women. Women with vaginal dysbiosis also had elevated vaginal pH and were more frequently infected with high-risk HPV. Furthermore, we observed associations of multiple people in a household, lower level of education, and high parity with vaginal dysbiosis and abundance of specific bacterial species. Finally, women with dysbiotic microbiota presented with elevated vaginal levels of proinflammatory cytokines. Altogether, these findings indicate an interplay between HPV, vaginal microbiota, and host defense, which may play a role in the cervical cancer disparity among Native American women. Future longitudinal studies are needed to determine the mechanistic role of vaginal microbiota in HPV persistence in the context of social determinants of health toward the long-term goal of reducing health disparities between non-Hispanic White and Native American populations. Prevention Relevance: Cervical cancer disproportionally affects Native American women. Sociodemographic and behavioral factors might contribute to this disparity via alteration of vaginal microbiota. Here, we show the association between these factors and vaginal dysbiosis and immune activation, which can be implicated in high-risk HPV infection among Native American and other racial/ethnic populations., (©2024 The Authors; Published by the American Association for Cancer Research.)

High-risk human papillomavirus (HR-HPV) testing, utilizing both DNA and RNA methods, offers enhanced sensitivity compared to cytology for detecting high-grade cervical intraepithelial neoplasia (CIN2+). Meanwhile, HR-HPV E6 and E7 mRNAs are more likely to differentiate the transient infection from the persistent than DNA. Aptima HPV can not only detect HPV mRNA but also HPV DNA though it is much more efficient at detecting HPV RNA than DNA. Currently, there are few studies on the distribution of HPV E6 and E7 mRNA and DNA in the same individual. It is interesting to compare the clinical performance of the Onclarity and Aptima HPV assays and to assess variations in viral load across different histological grades at both DNA and mRNA levels. The analysis included 1607 women (902 from a cervical cancer screening population and 705 inpatients and outpatients), with cervical cytological samples tested using the Aptima and Onclarity HPV assays. Both assays demonstrated high agreement for HPV types 18/45 and 16. Signal-to-cutoff (S/CO) values and Ct values for various HR-HPV types increased with histological severity from normal tissue to cancer. Notably, HPV18 Ct values exceeded those for HPV16 and 45 in women with ≥ CIN1 lesions but decreased sharply in cancer cases. Across the screening population, both assays showed similar sensitivity and predictive values for detecting CIN2+ lesions. The area under the curve (AUC) for CIN2+ and CIN3+ detection in the study population was robust (CIN2+: 0.880, 0.863; CIN3+: 0.881, 0.863). The DNA level for various HR-HPV types increased with histological severity from normal tissue to cancer, which might impact the performance of Aptima HPV assay. Both assays showed similar sensitivity and predictive values for detecting CIN2+ lesions., (© 2024 Wiley Periodicals LLC.)

The cervicovaginal microbiome (CVM) may contribute to human papillomavirus (HPV)-associated cervical carcinogenesis. We summarized the literature on the CVM in cervical carcinogenesis by searching Medline, Web of Science, and Embase for articles that sequenced the CVM using metagenomics. Additionally, we identified studies assessing the diagnostic role of the CVM in cervical carcinogenesis by searching PubMed. We performed an environmental scan of Google and Google Scholar to review common CVM characterization techniques. Twenty-eight records presented or summarized associations between the CVM and HPV acquisition, prevalence, persistence, clearance, and cervical lesions or cancer, while three studies identified bacterial taxa detecting high-risk HPV prevalence or cervical lesions. The area under the curve ranged from 0.802 to 0.952. 16S ribosomal RNA gene sequencing and whole metagenome sequencing have sufficient resolution to study the CVM bacteriome. Bacterial communities may have important implications in cervical cancer; however, there is a need for methodological standardization for CVM characterization., (© 2024 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.)

Human papillomavirus (HPV) vaccines received regulatory approval and were recommended for use in young girls nearly 2 decades ago. Uptake is mostly high in resource-rich settings. In resource-limited settings, where the burden of cervical cancer is disproportionately high, access to and uptake of HPV vaccines are nowhere near satisfactory, despite evidence that HPV vaccination is highly cost-effective and a significant value-for-money investment. The discovery that only a single dose of the HPV vaccines may be needed to confer adequate protection may make equitable access to HPV vaccines possible. Indeed, the recent World Health Organization recommendation allowing for 1 or 2 doses is already gaining traction. This monograph aims to update the state of the science related to single-dose HPV vaccine protection and includes both primary data and modeling efforts that address key gaps in the knowledge regarding 1) durability of protection of a single dose of the HPV vaccine, 2) single-dose HPV vaccine effectiveness in both high-income and low-income settings, 3) implementation of single-dose HPV vaccination, and 4) how to accelerate control of cervical cancer by integrating a 1-time screen for cervical disease. The content published in this monograph will continue to advance the science of HPV vaccination and will be vital as new countries make informed decisions about how best to use this remarkable vaccine., (Published by Oxford University Press 2024.)

Background: While recommending a human papillomavirus (HPV) single-dose vaccination schedule in 2022, the World Health Organization highlighted the need for long-term follow-up studies to monitor waning of protection. We report on vaccine efficacy against HPV infections in 1-, 2-, and 3-dose schedules and protection against cervical precancers at a median follow-up of 12 years postvaccination., Methods: This randomized multicenter study in India was originally designed to vaccinate unmarried girls aged 10-18 years with either 2 or 3 doses of quadrivalent HPV vaccine. A ministerial decree to halt vaccination in trials resulted in the creation of cohorts receiving different doses, including just a single dose. Cohorts were assessed for incident and persistent infections by genotyping cervical samples collected yearly for 4 consecutive years after participants were married. Cervical screening with an HPV test was initiated at age 25 years for married participants. Age- and site-matched unvaccinated married women were recruited to be compared with vaccinated cohorts. Vaccine efficacy was assessed using proportional incidence ratios., Results: The number of participants in the 1-, 2- (at 0 and 6 months), and 3-dose cohorts was 4949, 4980, and 4348, respectively. Of the recipients, 71%-82% in the different cohorts were eligible to provide samples for genotyping. Vaccine efficacy against persistent HPV 16 and 18 infection was 92.0% (95% confidence interval [CI] = 87.0% to 95.0%) in 3022 recipients of the single dose; and comparable with that observed in the 2-dose arm (94.8%, 95% CI = 90.0% to 97.3%) and the 3-dose arm (95.3%, 95% CI = 90.9% to 97.5%). No high-grade precancer associated with HPV 16 and 18 was detected among vaccinated participants compared with 8 precancers detected among the unvaccinated women., Conclusion: This observational cohort study has established that a single dose of HPV vaccine provides high protective efficacy against persistent HPV 16 and 18 infections and associated neoplasia 15 years postvaccination., (© The Author(s) 2024. Published by Oxford University Press.)

Background: We simulated the impact of hypothetical waning scenarios of a 1-dose human papillomavirus (HPV) vaccination paired with switching to 2-dose mitigation strategies guided by empirical vaccine trial reporting timelines., Methods: Using 2 independent mathematical models fitted to a high-burden setting, we projected the cumulative cervical cancer cases averted over 85 years for alternative HPV vaccination scenarios under 2 program adoption timelines: 1) de novo introduction of a 1-dose HPV vaccination and 2) a switch from an existing 2-dose HPV vaccination program to a 1-dose vaccination. We assumed 80% vaccination coverage with the bivalent vaccine and an average duration of a 1-dose HPV vaccine protection of either 30 or 25 years with 100% efficacy. We varied the eligible age group(s) at program introduction and the 2-dose mitigation (single-age cohort or multi-age cohort). If needed for mitigation, reintroduction of 2-dose vaccination was assumed to occur in 2036 (ie, 30 years after initiation of the Costa Rica Vaccine Trial)., Results: Under both vaccine adoption timelines, the models projected that countries could achieve the same level of health benefits by switching to 2 doses in 2036 using a multi-age cohort approach as with initiating a 2-dose or 1-dose vaccination program with no waning. With only a single-age cohort 2-dose mitigation approach, 98%-99% of cases would be prevented compared with the health benefits of 2 doses or a noninferior, durable 1 dose., Conclusions: Countries hesitant to adopt a 1-dose HPV vaccination program may have opportunities to leverage the benefits and efficiency of a 1-dose schedule while awaiting longer-term reporting from 1-dose durability studies, including Costa Rica Vaccine Trial., (© The Author(s) 2024. Published by Oxford University Press.)

Human papillomavirus (HPV) prophylactic vaccines were first licensed in 2006 with the primary goal of preventing HPV-related cancers, with cervical cancer accounting for the highest morbidity and mortality globally. Six HPV vaccines have been licensed; 4 of these have been prequalified by the World Health Organization, and additional products are in the pipeline. This article provides an overview of HPV vaccine coverage and current and anticipated vaccine supply vs expected demand. Given that the 2022 World Health Organization position paper on HPV vaccines includes a 1-dose regimen as an alternate schedule, we will discuss the evidence for using licensed vaccines in single-dose regimens and the approach to generating similar supportive data for other current and future vaccines. The broad adoption of a single-dose HPV vaccine regimen would expand access to vaccines by improving the supply-demand balance, increasing affordability, and simplifying logistics, which will ultimately impact HPV-related morbidity and mortality., (© The Author(s) 2024. Published by Oxford University Press.)

Background: A concern in high-income countries is that switching to 1-dose human papillomavirus (HPV) vaccination could cause a rebound in HPV infection and cervical cancer if 1-dose efficacy or duration were inferior to 2 doses. Using mathematical modeling and up-to-date trial-based data, we projected the population-level effectiveness of switching from 2-dose to 1-dose vaccination under different vaccine efficacy and duration assumptions in high-income countries., Methods: We used HPV-ADVISE (Agent-based Dynamic model for VaccInation and Screening Evaluation), a transmission-dynamic model of HPV infection and cervical cancer, varying key model assumptions to identify those with the greatest impact on projections of HPV-16 and cervical cancer incidence over time: 1) 1-dose vaccine efficacy and vaccine duration, 2) mechanisms of vaccine efficacy and duration over time, 3) midadult (>30 years of age) sexual behavior, 4) progression to cervical cancer among midadults, and 5) vaccination coverage and programs., Results: In high-income countries, 1-dose vaccination would cause no appreciable rebound in HPV-16 infection, except for a limited rebound under the most pessimistic assumptions of vaccine duration (average, 25 years), because 1) the switch would occur when HPV prevalence is low because of high 2-dose vaccination coverage and 2) individuals would be protected during their peak ages of sexual activity (<35 to 40 years of age). Our model projects a more limited rebound in cervical cancer because of a shift to older age at infection, resulting in fewer life-years left to potentially develop cancer. Projections were robust when varying key model assumptions., Conclusions: High protection during peak ages of sexual activity in high-income countries would likely mitigate any potential rebounds in HPV infection and cervical cancer under the most pessimistic assumptions of 1-dose efficacy and duration., (© The Author(s) 2024. Published by Oxford University Press.)

Objective: We explored the prevalence of human papillomavirus (HPV) infection among women in Jinshan District, Shanghai., Methods: We analyzed all HPV testing samples sent from our unit between December 2023 and April 2024. We reported the HPV prevalence overall, by age, and by subtype., Results: In total, 3788 women aged 16 to 90 years had HPV test results. The prevalence of infection with any HPV subtype was 17.9%. The HPV prevalence by age group was: ≤30 years, 15.4%; 31-40 years, 14.7%; 41-50 years, 17.0%; 51-60 years, 22.4%; >60 years, 31.0%. Among HPV-positive women, 80.6% had infection with one subtype, 16.4% had dual infection, and 3.1% had three or more subtypes detected. We found 640 cases (16.9%) of infection with high-risk HPV subtypes and 139 cases (5.04%) of infection with low-risk HPV subtypes. The most common high-risk subtypes were HPV 52, 53, 58, and 16; the most common low-risk subtypes were HPV 81, 70, and 42., Conclusion: We detected ≥1 HPV subtype among most women in our study. The prevalence of HPV was lowest in younger women and highest in women age >60 years. Tailored strategies for older women are needed to prevent HPV infection and cervical cancer., Competing Interests: Declaration of conflicting interestThe authors declare that there is no conflict of interest.

Background/aim: Cervical cancer is the third leading cause of cancer-related death in women worldwide. Nearly all cases of cervical cancer are due to infection with human papillomavirus (HPV). Nowata110 has shown breakthrough therapeutic efficacy in phase II clinical study against plantar warts, with no reported side effects. This study evaluated the effectiveness of Nowarta110 in killing cultured HPV-transformed cancer cells and its anti-cancer effects in mice, using both vaginally engrafted and subcutaneously implanted animal cancer models., Materials and Methods: Nowata110 is a novel compound composed of colloidal silver and fig extract. The cytotoxic properties of Nowarta110 were evaluated on HPV-16 and HPV-18-transformed human cancer cells (ARPE-19/HPV-16 and HeLa cells, respectively). The therapeutic potential of Nowarta110 in vivo was evaluated following the engraftment of ME-180 epidermoid carcinoma cells in the mouse vagina or their subcutaneous implantation. Nowarta110 treatment was initiated when the tumor reached an approximate volume of 65 mm 3 Results: Our data showed that HPV16-expressing human retinal pigmented epithelial cells are susceptible to Nowarta110-induced cell death, with a reduction in cell viability observed at 1% Nowarta110 and a complete absence of viable cells at 5% Nowarta110. In HPV18-expressing HeLa cells, Nowarta110 caused significant and rapid cell death at a dose of 5%, whereas lower doses of 1% did not produce the same effects. The results from animal studies indicated that Nowarta110 effectively induced tumor regression in both the intravaginal and subcutaneous tumor models., Conclusion: Nowarta110 effectively induced cell death in HPV-16 and HPV-18-transformed human cancer cells. It also effectively induced tumor regression in mouse models with intravaginally engrafted or subcutaneously implanted cancer cells. Considering the high prevalence of HPV-induced cervical dysplasia and cancer and the lack of treatment, clinical studies to promote the implementation of Nowarta110 are warranted., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Human papillomavirus-independent (HPVI) squamous cell carcinoma (SCC) and adenosquamous carcinoma (ASC) of the uterine cervix are extremely rare. The aim of this study was to comprehensively describe the clinicopathological features, patient outcomes, and immunophenotypes of HPVI SCC and ASC., Patients and Methods: We found four and two patients with HPVI SCC and ASC, respectively, and reviewed their electronic medical records and pathology slides. We also performed immunostaining for p16 and p53., Results: All except one patient underwent surgery. Two, one, and one patients with HPVI SCC were diagnosed as having IIIC1, IVA, and IVB diseases, respectively. Two patients with HPVI SCC experienced recurrences, and died of disease within nine months after treatment initiation. Both patients with HPVI ASC developed lung metastasis at four months post-operatively. HPVI SCCs and the squamous component of HPVI ASCs showed keratinizing, condylomatous, or poorly differentiated morphology. The glandular component of HPVI ASCs was gastric-type endocervical adenocarcinoma. None of the six tumors exhibited block positivity for p16. Two HPVI SCCs and one HPVI ASC displayed aberrant p53 expression., Conclusion: HPVI SCC is a rare and aggressive cervical malignancy that presents initially as advanced-stage disease with poor prognosis. Although the patients with initial stage I and II HPVI ASC were treated with curative intent, distant metastases appeared in the lungs during the early course of treatment. Further investigations are necessary to clarify the association between histological features and clinical behavior of HPVI ASC., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

More than 99 % of precancerous cervical lesions are associated with human papillomavirus (HPV) infection, with HPV types 16 and 18 (especially type 16) found in over 70 % of cervical cancer cases globally. The growth of HPV-positive cervical cancer depends on the sustained expression of the viral oncogenes E6 and E7, which are key factors in maintaining the malignant phenotype of HPV-positive tumor cells. E6 and E7 oncoproteins can cause the degradation of the tumor suppressor gene p53 and the inactivation of pRb, respectively, thereby inducing carcinogenesis. However, the inhibition of p53 and pRb cannot fully explain the oncogenic mechanism of cervical cancer. Although the development of the HPV vaccine has controlled the incidence of HPV infection, its application and widespread adoption remain limited. In addition, many developing countries cannot afford the cost of vaccines. More importantly, the vaccine only prevents HPV infection and does not provide an effective treatment for patients who are already infected or have cervical cancer. Therefore, HPV-related diseases, especially cervical cancer, remain a serious challenge. This article reviews the role of glucose metabolism changes and key molecular events in HPV-induced cervical cancer, summarizes potential targets for the treatment of cervical cancer, and provides strategies for future clinical treatment. It also offers a theoretical basis for research into cervical cancer and other HPV-related tumors. Furthermore, we discuss potential treatments for HPV-associated cervical cancer through targeted metabolic pathways and analyze the risks and challenges of current targeted glucose metabolism therapies for cervical cancer., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objectives: In 2021, the World Health Organisation (WHO) updated its guidelines for cervical screening from cytology testing to primary high-risk human papillomavirus (HR-HPV) testing. This change in testing has effectively led to a 'new disease' as women are now aware of having a virus that induces changes that can cause cancer, which they would have been unaware of previously. While current management involves a 'watch and wait' approach and no active treatment, the anxiety associated with having HR-HPV may prompt some women to seek 'treatments' outside the screening programme. ● to identify potential treatment options available for women with persistent HR-HPV and/or low-grade cervical intraepithelial neoplasia (CIN), i.e. ≤CIN 1. ● to determine the clinical effectiveness of these treatments, namely by: ◦ HR-HPV clearance rate, and/or: ◦ CIN regression., Methods: We searched MEDLINE, PubMed, EMBASE, Web of Science and the Cochrane Library. We included cohort studies and randomised controlled trials (RCTs) only. Records (n = 2135) were screened in Rayyan by two independent reviewers. Quality assessment was conducted using the ROBINS-I tool and the ROB-2 tool., Results: 12 studies (four cohort studies and eight RCTs) were included: six oral medications, two topical medications, one vaccination, and three non-surgical device treatments. Meta-analysis revealed that some therapeutic interventions, including vaginal gels, photodynamic therapy, and some oral medications, may lead to earlier resolution of persistent HR-HPV and regression of low-grade CIN when compared with natural clearance., Conclusion: This review can better inform discussions with HR-HPV+ women and answer their questions about alternatives to surveillance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Cervical cancer, originating from the epithelial tissue of the uterine cervix, constitutes the most commonly diagnosed malignancy among women worldwide. The predominant etiological factor underpinning cervical carcinogenesis is persistent infection with high-risk human papillomavirus (HPV) genotypes, notably HPV-16 and HPV-18. Oncoproteins encoded by high-risk HPV interfere with multiple essential cellular signaling cascades. Specifically, E5, E6, and E7 proteins disrupt the signaling pathways like p53, retinoblastoma tumor suppressor protein (pRB), The phosphoinositide 3 kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR), epidermal growth factor receptor (EGFR), mitogen-activated protein kinases (MAPK)/extracellular signal-regulated kinases (ERK), and Wnt/β-catenin, promoting HPV-mediated carcinogenesis. This dysregulation disrupts cell cycle control, apoptosis, and metastasis through modulation of microRNAs (miRNA) and key cellular processes. The novel therapeutic interventions for HPV prevention and detection are fundamental to patient management. RNA-based treatment modalities offer the potential for manipulating critical pathways involved in cervical carcinogenesis. RNA therapeutics offer novel approaches to drug development by targeting intracellular genetic elements inaccessible to conventional modalities. Additional advantages include rapid design, synthesis, and a reduced genotoxic profile compared to DNA-based therapies. Despite beneficial attributes, system stability and efficient delivery remain critical parameters. This study assessed the intricate relationship between HPV, cervical cancer, and various signaling pathways. The study explores miRNAs' diagnostic and therapeutic potential, mall interfering RNAs (siRNAs), and long non-coding RNAs (lncRNAs)in cervical cancer management. The review highlights the prospect of RNA-targeted therapies to modulate specific cancer signaling pathways. This approach offers a novel strategy for cervical cancer treatment through precise regulation of cancer signaling. Future research should concentrate on developing RNA-targeted interventions to improve cervical cancer treatment outcomes through increased therapeutic efficacy and specificity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier GmbH.)

The progression of high-grade squamous intraepithelial lesion (HSIL) to invasive cervical cancer (ICC) is a complex process involving persistent human papillomavirus (HPV) infection and changes in signal transduction regulation, energy and material metabolism, cell proliferation, autoimmune, and other biological process in vaginal microenvironment and immune microenviroment. Signaling pathways are a series of interacting molecules in cells that regulate various physiological functions of cells, such as growth, differentiation, metabolism, and death. In the progression of HSIL to ICC, abnormal activation or inhibition in signaling pathways plays an essensial role. This review presented some signaling pathways related to the malignant progression of HSIL to ICC, including p53, Rb, PI3K/AKT/mTOR, Wnt/β-catenin, Notch, NF-κB, MAPK, TGF-β, JAK-STAT, Hippo, and Hedgehog. The molecular mechanisms involved in the biological process of pathway regulation were also analyzed, in order to illustrate the molecular pathway of HSIL progression to ICC and provide references for the development of more effective prevention and treatment methods., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

High-risk human papillomavirus (HPV) screening is crucial for cervical cancer prevention. However, laboratory-based nucleic acid amplification tests (NAATs) require costly equipment, designated lab space, and skilled personnel. Additionally, cervical swabs collected by healthcare professionals can be inconvenient, uncomfortable, and reduce privacy, limiting broader application and patient compliance. A SlipChip-based Integrated Point-of-Care (SIPOC) system featuring an injection-molded SlipChip is presented with preloaded reagents for nucleic acid extraction and a portable four-channel real-time quantitative PCR instrument for detection. This system incorporates a self-sampling method that allows participants to collect their own vaginal swabs, with the β-Globin gene as a control. After testing 130 participants for HPV-16 and HPV-18, 97.7% of the self-collected samples are valid. Among valid samples, 25 tested positive for HPV-16 and 9 for HPV-18. Compared to Roche's standard HPV PCR test, the SIPOC system shows 100% positive predictive value (PPV) for both HPV-16 and HPV-18 and negative predictive values (NPVs) of 99.0% and 99.1%, respectively. This system is promising for HPV screening in resource-limited settings and adaptable for other point-of-care NAAT applications, including home testing., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Background: Although therapeutic human papillomavirus vaccines could offer a noninvasive treatment for patients with cervical intraepithelial neoplasia, none has been clinically implemented. Oral administration of the therapeutic human papillomavirus vaccine IGMKK16E7 results in the histological regression of human papillomavirus 16-positive cervical intraepithelial neoplasia 2/3 to normal (complete response). We investigated biomarkers that could predict complete response after oral administration of IGMKK16E7., Methods: Forty-two patients administered high-dose oral IGMKK16E7 in a phase I/II trial were included. Cervix-exfoliated cells were collected before vaccine administration. Gene expression of CD4, CD8, FOXP3, programmed cell death 1 protein, CTLA4, CD103, CD28, CD80, CD86, and programmed cell death 1 ligand 1 in the cells was measured by quantitative reverse transcriptase-polymerase chain reaction. Receiver operating characteristic curve analysis and Mann-Whitney tests were used to explore potential biomarkers. Pearson correlation coefficient analysis was used to correlate gene expression profiles with clinical outcome., Results: The only predictive biomarker of vaccine response for which receiver operating characteristic curve analysis showed significant diagnostic performance with histological complete response was CD86 (area under the curve = 0.71, 95% confidence interval = 0.53 to 0.88, P = .020). Patients with complete response had significantly lower CD86 expression (CD86-low) than patients with no complete response (P = .035). The complete response rates for CD86-low and CD86-high patients were 50% and 19%, respectively, and CD86-low patients had a significantly higher complete response rate (P = .047). Compared with all patients, the CD86-low group had a 1.5-fold increase in the complete response rate. Gene expression of CD86 and CTLA4 showed the strongest positive correlation with clinical outcomes in the incomplete response group (P < .001)., Conclusion: Low expression of CD86 in exfoliated cervical cells can be used as a pretreatment biomarker to predict histological complete response after IGMKK16E7 administration., (© The Author(s) 2024. Published by Oxford University Press.)

Human Papillomavirus (HPV) is a widespread infection associated with various cancers, including cervical, oropharyngeal, anal, and genital cancers. This infection contributes to 5 % of global cancer cases annually, affecting approximately 625,600 women and 69,400 men. Cervical cancer remains the most prevalent HPV-linked cancer among females, with the highest incidence seen in low and middle-income countries (LMICs). While most HPV infections are transient, factors such as HPV variants, age, gender, and socioeconomic status influence transmission risks. HPV is categorized into high-risk (HR-HPV) and low-risk types, with strains like HPV 16 and 18 displaying distinct demographic patterns. The intricate pathogenesis of HPV involves genetic and epigenetic interactions, with HPV oncogenes (E6 and E7) and integration into host DNA playing a pivotal role in driving malignancies. Early diagnostics, utilizing HPV DNA testing with surrogate markers such as p16, and advanced molecular techniques like PCR, liquid biopsy, and NGS, significantly impact the management of HPV-induced cancers. Effectively managing HPV-related cancers demands a multidisciplinary approach, including immunotherapy, integrating current therapies, ongoing trials, and evolving treatments. Prevention via HPV vaccination and the inclusion of cervical cancer screening in national immunization programs by conventional Pap smear examination and HPV DNA testing remains fundamental.Despite the preventability of HPV-related cancers, uncertainties persist in testing, vaccination, and treatment. This review article covers epidemiology, pathogenesis, diagnostics, management, prevention strategies, challenges, and future directions. Addressing issues like vaccine hesitancy, healthcare disparities, and advancing therapies requires collaboration among researchers, healthcare providers, policymakers, and the public. Advancements in understanding the disease's molecular basis and clinical progression are crucial for early detection, proper management, and improved outcomes., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Durre aden reports administrative support was provided by HIMSR. Durre aden reports a relationship with HIMSR that includes: employment. Durre aden has patent na pending to not applicable. none, (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Background: Organized cervical cancer (CxCa) screening is the most effective secondary prevention method to decrease the disease incidence and mortality. Screening for infection with 14 high-risk HPV genotypes (hrHPV) is recommended as primary screening test. Since only ca. 6 % of HPV-positive (HPV+) women will develop a high-grade lesion in 5 years, triage is critical for risk stratification and management of colposcopy resources. Dual staining (DS) p16/Ki67 cytology is an alternative to Papanicolau cytology (PAP) for triage of HPV+women, with potential improvements in sensitivity and specificity, and optimization of colposcopy referrals., Objectives: To compare PAP vs DS cytology in terms of (i) optimization of referrals for colposcopy and (ii) risk stratification to better define the follow-up interval., Study Design: Retrospective analysis of the CxCa screening database of Centro Hospitalar Universitário de Coimbra (CHUC), one of the centralized diagnostic laboratories for the CxCa screening program of the central region of Portugal, between July 2019 and May 2023. At CHUC, since July 2019, all samples from hrHPV+women have been triaged with liquid PAP and tested with DS cytology., Results: At baseline (1032 HPV+women), 1028 women were tested with DS: 739 women were DS negative (DS-) [70.7 % with normal PAP cytology (NILM) and 29.3 % with abnormal PAP cytology (ASC-US+)], and 289 were DS positive (DS+) (1.1 % NILM and 98.6 % ASC-US+). DS positivity as referral criterion for colposcopy instead of ASC-US+would have reduced the number of colposcopies by 39.4 % overall and by 48.3 % for other 12 hrHPV, while improving the number of colposcopies per HSIL (3.9 vs. 2.4 overall and 4.9 vs. 2.9 for other 12 hrHPV). In this cohort, if the follow-up interval for women positive for other 12 hrHPV+and DS- would have been extended from 1 to 3 years, 799 follow-up consultations, 799 HPV re-tests, and 277 colposcopies (-64.7 %) would have been avoided, with an overall risk of missed HSIL lesions of 2.2 %., Conclusions: Triage with DS allows the optimization of colposcopy referrals and a safe extension of the follow-up interval to 3 years for other 12 hrHPV+/DS- women, eliminating the need for annual re-testing for many women., Competing Interests: Declaration of competing interest The authors declare that the study has been conducted in accordance with the principles set forth in the Helsinki Declaration. BS, TR, FS, FA, and GF declare no conflicts of interest regarding the publication of this study. DO and CC are employees of Roche Diagnostics, Portugal. No funding to declare., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: This study aims to evaluate the therapeutic outcomes of Paiteling and CO2 laser therapy on high-risk human papillomavirus., Methods: We retrospectively analyzed the data of 558 patients with HR-HPV low-grade squamous intraepithelial neoplasia (CIN1) from 2021 to 2023. Patients were selected and put into two groups: Paiteling and CO2 laser. Out of the 558 patients who were included in our final study, 239 (42.8 %) were treated with Paiteling, and 319 (57.2 %) were treated with CO2 laser vaporization. The mean age was 49.55 ± 12.10 years old. We observed that 27 (4.83 %) were younger than 30 years and 531 (95.1 %) were older than 30 years. We reviewed the patient's results at intervals of 3 months, 6 months, 12 months, and 24 months after each therapy. The results of the recurrence rate, effective viral clearance rate, and the effectiveness of both therapies on low-grade cervical lesions were determined using multivariate and univariate cox-regression analysis. The Kaplan-Meier curve was used to determine the HR-HPV conversion rate of each therapy., Results: The median time for HR-HPV clearance was 6.00 months (95 % CI: 4.26-6.89) in the Paiteling group and 9.00 months (95 % CI: 15.92-22.67) in the CO2 laser group. There was a significant difference between the two groups (χ2 = 25.118, p-Value = 0.000). The HR-HPV clearance rate during 6-12 months for Paiteling and CO2 laser was 100 (55.6 %) and 80 (44.4 %), respectively. The clearance rate for both therapies from 6 to 18 months was statistically significant (6-12 months: p < 0.010, 12-18 months: p < 0.011). The Paiteling HR-HPV negative rate over 24 months 214 (89.5 %) is higher than CO2 laser 176 (55.2 %). Paiteling has a 5.4 % re-infection rate, which is marginally lower than the 5.6 % rate for CO2 lasers. The clearance rate for both therapies from 12 to 18 months [Paiteling: 20 (4.7 %) to 10 (3.6 %) and CO2 laser: 22 (8.4 %) to 15 (4.2 %)] was also significant (p < 0.011). The percentage of persistent Hr-HPV clearance rate for Paiteling patients was higher than carbon dioxide laser vaporization. No severe side effects were reported by the Paiteling patients compared to laser vaporization. This is due to the fact that Paiteling, as a traditional Chinese medicine, is a topical, non-invasive medicine, thus preserving the integrity of the cervix., Conclusions: Paiteling is an effective noninvasive therapy that can clear persistent HR-HPV associated with cervical low-grade squamous lesions in a relatively shorter period of time compared to CO2 laser ablation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: Human papillomavirus (HPV) is the most common sexually transmitted infection, responsible for multiple HPV-related diseases, including almost all cervical cancers. The highly effective HPV vaccination has been recommended under the German HPV national immunization program (NIP) since 2007 and is reimbursed by health insurances. Vaccination uptake rates, however, remain suboptimal and data on the real-world impact of HPV vaccination in Germany are lacking. This study aims to demonstrate the population-level impact of Germany's NIP on HPV-related anogenital diseases among young women., Methods: Retrospective claims data analysis using a classic impact study design comparing disease prevalence among 28- to 33-year-old women before and after introduction of the HPV-immunization program in Germany. Claims data representing approximately two thirds of German health insurances were used. HPV-related disease outcomes included cervical cancer and high grade precancers (cervical intraepithelial neoplasia (CIN) 2+), anogenital warts, as well as vulvar, vaginal, and anal precancer/cancer., Results: Significant declines were seen for CIN2+, anogenital warts, and vaginal precancer/cancer. Prevalence of CIN2+ declined 51.1% from 0.92% (95% CI = 0.78%, 1.08%) to 0.45% (95% CI = 0.38%, 0.53%). There was a 38.6% decline in anogenital warts prevalence from 0.44% (95% CI = 0.36%, 0.54%) to 0.27% (95% CI = 0.22%, 0.32%) and 75.0% decline in vaginal precancer/cancer prevalence from 0.04% (95% CI = 0.02%, 0.07%) to 0.01% (95% CI = 0.00%, 0.02%)., Conclusion: The German HPV-immunization program has led to significant declines in female anogenital disease among young women in Germany, highlighting the importance of the vaccination. Moreover, the data suggest that increasing vaccination coverage in Germany could further strengthen the public-health impact of its HPV-immunization program., (© 2024. Merck & Co., Inc., Rahway, NJ, USA and its affiliates & Monika Hampl 2024.)

This study was conducted to determine women's health beliefs about HPV and HPV vaccination and factors associated with health beliefs. This cross-sectional study was conducted with 300 women aged 21-64 in Turkey. Data were collected using the human papillomavirus (HPV) knowledge scale (HPV-KS) and the health belief model scale for human papillomavirus and its vaccination (HBMS-HPVV). The mean age of the women who participated in the study was 35.16 ± 9.52 years. Of them, 72.3% heard of the HPV test, 30.3% had an HPV test, 62% heard of HPV vaccination, and 9.7% had HPV vaccination. Educational level, hearing about the HPV vaccine, and HPV knowledge level were significant predictors of perceived benefit (p < .001). HPV knowledge level significantly predicted perceived susceptibility (p < .001). HPV knowledge level and hearing about HPV tests and vaccines were significant predictors of perceived severity (p < .001). A high level of education, a high level of HPV knowledge, and hearing about HPV tests and the HPV vaccine positively affect women's health beliefs. Health belief model-based education programs should be used to improve women's HPV knowledge and health beliefs about HPV and the HPV vaccine. In addition to women's health beliefs, cervical cancers can only be prevented by including the HPV vaccine in national immunization programs and increasing the coverage of HPV screening tests., (© 2024 Wiley Periodicals LLC.)

Purpose of Review: To highlight recent data on HPV infection and cervical precancerous lesions in adolescents with HIV, and priorities for primary and secondary HPV prevention., Recent Findings: Incident and persistent high-risk HPV infections and cervical abnormalities are higher among young women with perinatally acquired HIV compared to their HIV-negative peers; data on HPV among males with perinatally acquired HIV are scarce. HPV vaccination is highly effective in preventing HPV-related disease, but antibody titers may decline in people with HIV. It remains unclear if emerging recommendations to reduce vaccine schedules from three doses to two or one dose are appropriate for children and adolescents with perinatally acquired HIV. Due to higher risks of HPV-related cancers, screening guidelines for cervical cancer differ in their frequency and age at initiation for women with HIV, but there are no recommendations for women with perinatally acquired HIV; nor for anal cancer screening for men with perinatally acquired HIV., Summary: Data on the effectiveness of reduced HPV vaccine schedules in children and adolescents with HIV are needed. Implementation research to guide strategies for vaccination, screening, and treatment should include children, adolescents, and young adults with perinatally acquired HIV to ensure they are not left behind., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To compare the health impact and economic benefits among individuals who did not receive the human papillomavirus (HPV) vaccine to those who received a single dose, or 2 doses. The comparison was stratified by 4 types of vaccine in conjunction with primary HPV screening in a low/middle-income country setting., Methods: A Markov model was employed to simulate HPV infection and cervical cancer in a cohort of 100,000 12-year-old girls free of HPV. The study scrutinized 9 strategies: 1 dose and 2 doses of 2vHPV (Cervarix ® ), 2vHPV (Cecolin ® ), 4vHPV (Gardasil ® ), 9vHPV vaccine (Gardasil9 ® ), and no vaccination. The primary outcome measure was the quality-adjusted life year (QALY) of each strategy. Incremental cost-effectiveness ratios were estimated over a lifetime horizon, accompanied by sensitivity analyses conducted., Results: All vaccination programs yielded 41,298-71,057 QALYs gained accompanied by cost savings of 14,914,186-19,821,655 USD compared to no vaccination. Administering 2 doses of 9vHPV vaccine emerged as the most cost-effective strategy, boasting 406 USD/QALY, within a lower willingness to pay threshold. Sensitivity analysis demonstrated an 80% probability of the cost-effectiveness of the 2 doses of 9vHPV vaccine regimen. Furthermore, uncertainty around the costs of vaccination and vaccine efficacy exerted the most substantial influence on the cost-effectiveness findings., Conclusion: Oping for 2 doses of 9vHPV vaccine in conjunction with a primary HPV screening represents the most cost-effective option for implementing a school-based HPV vaccination program targeting 12-year-old girls in Thailand. Such findings provide valuable insights for policymakers in the realm of cervical cancer prevention., Competing Interests: No potential conflict of interest relevant to this article was reported., (© 2024. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

Objective: We aimed to investigate differences between HPV-16 mono- and HPV-16/18 co-infections in terms of cervical dysplasia and invasive cancer., Methods: This multicentre, retrospective study spanned from December 2017 to December 2020, involving women who visited gynaecological oncology clinics for colposcopy with either HPV-16 or HPV-16/18 positivity. A total of 736 patients, 670 in Group 1 (HPV-16 positivity) and 66 in Group 2 (HPV-16/18 positivity), were compared for the presence of CIN2+ lesions detected by colposcopic biopsy or endocervical curettage (ECC). Exclusions included hysterectomized patients, those with prior gynaecological cancers, and patients with HPV positivity other than types 16 and 18., Results: Among the included patients, 42.4% had a diagnosis of CIN2+ lesions. The cytology results demonstrated abnormal findings in 45.3% in Group 1 and 42.2% in Group 2, with no significant difference between the groups. ECC revealed CIN2+ lesion in 49 (8.7%) patients in group 1, while only 1 (1.7%) patient had CIN2+ lesion in group 2. There was no difference between 2 groups in terms of ECC result (p = 0.052). In group 1, 289 (43.1%) patients had CIN2+ lesion, while 23 (34.8%) patients had CIN2+ lesions in group 2. There was no difference between group 1 and 2 in terms of diagnosis of CIN2+ lesions (p = 0.19)., Conclusion: This multicentre retrospective study found no significant differences between HPV-16 mono- and HPV-16/18 co-infections regarding cervical pathologies. Larger studies are needed to validate and further explore these findings., (© 2024 John Wiley & Sons Ltd.)

Objective: High-risk human papillomavirus (HR-HPV) infection is a leading cause of cervical cancer, of which human papillomavirus (HPV)-16 and HPV-18 account for about 70% of cases. Since HPV infection is common, it is important to focus on the HPV genotypes that pose the highest risk for effective cervical cancer screening. In this study, we evaluated the clinical usefulness of HPV-16/HPV-18 genotyping for cervical cancer screening., Methods: A total of 86,022 women aged 25 years or older was analyzed in this study. Sensitivity, specificity, positive predictive value, and negative predictive value of HPV genotyping and cytology were analyzed. In addition, we subdivided participants into two groups according to cytology results, negative for intraepithelial lesion of malignancy (NILM) and atypical squamous cells of undetermined significance (ASC-US), and analyzed absolute risk (AR) and relative risk (RR) of cervical intraepithelial neoplasia (CIN) 3 or worse according to HPV genotype., Results: The AR of CIN 3 or worse was 77.0 times higher in HR-HPV-positive compared to HR-HPV-negative. Compared to 12 other HR-HPV-positive, the AR of CIN 3 or worse was 4.2 times higher in HPV-16 and/or HPV-18 positive. This finding was more evident in women with NILM than in women with ASC-US. The RR of CIN 3 or worse was 7.0 in women with NILM and 4.5 in women with ASC-US., Conclusion: Regardless of the cytology results, the risk of CIN 3 or worse was higher in HPV-16/HPV-18 than in other HR-HPV. HPV-16/HPV-18 genotyping is recommended to screen women with a high risk of cervical cancer., Competing Interests: No potential conflict of interest relevant to this article was reported., (© 2024. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

Objective: This study aims to examine the relationship between human papillomavirus (HPV) testing attitudes and beliefs, knowledge, and vaccination attitudes., Design: This study was a cross-sectional design., Sample: This study was conducted between March 15, 2024, and June 2, 2024, through social media platforms such as Facebook, Instagram, Twitter, and Telegram, by sharing on forum pages, and involved 674 women who volunteered to participate., Measurements: The research data were collected using the "health belief model scale regarding HPV infection and vaccination (HBMS-HPVV)" and the "HPV Testing Attitudes and Beliefs Scale (HTABS)," which were developed by the researchers through a literature review., Results: The average age of the women participating in the study was 46.59 ± 11.15 years; 81.5% were married, 57.6% had no knowledge about cervical cancer, and 62.2% had no knowledge about the HPV vaccine, a protective vaccine against cervical cancer. The average scores for the subdimensions of severity, barriers, benefits, and susceptibility of the HBMS-HPVV were 3.19 ± 0.60, 2.96 ± 1.22, 2.29 ± 1.40, and 3.92 ± 0.49, respectively. The average scores for the subdimensions of personal barriers, social norms, confidence, and worries of the HTABS were 31.14 ± 19.27, 7.57 ± 4.47, 30.03 ± 7.18, and 11.91 ± 2.52, respectively. A statistically significant positive relationship was found between all HBMS-HPVV subdimensions and the HTABS subdimensions (p < 0.001)., Conclusion: The study found that as the perceived severity increases, the perceived benefits, susceptibility, and confidence increase, while the perceived barriers, personal barriers, social norms, and worries decrease. Based on these results, it is recommended that women's health nurses provide education and seminars to raise awareness about cervical cancer, early screening and diagnosis programs, and the HPV vaccine., (© 2024 The Author(s). Public Health Nursing published by Wiley Periodicals LLC.)

Cervical cancer screening programs, including triage tests, need redesigning as human papillomavirus (HPV)-vaccinated women are entering the programs. Methylation markers offer a potential solution to reduce false-positive rates by identifying clinically relevant cervical lesions with progressive potential. In a nested case-control study, 9242 women who received the three-dose HPV16/18-vaccine at ages 12-15 or 18 in a community-randomized trial were included. Subsequently, they were re-randomized for either frequent or infrequent cervical cancer screening trials. Over a 15-year post-vaccination follow-up until 2022, 17 high-grade squamous intraepithelial lesion (HSIL) and 15 low-grade (LSIL) cases were identified at the 25-year screening round, alongside 371 age and community-matched HPV16/18-vaccinated controls. Methylation analyses were performed on cervical samples collected at age 25, preceding histologically confirmed LSIL or HSIL diagnoses. DNA methylation of viral (HPV16/18/31/33) and host-cell genes (EPB41L3, FAM19A4, and miR124-2) was measured, along with HPV-genotyping. No HPV16/18 HSIL cases were observed. The predominant HPV-genotypes were HPV52 (29.4%), HPV59/HPV51/HPV58 (each 23.5%), and HPV33 (17.7%). Methylation levels were generally low, with no significant differences in mean methylation levels of viral or host-cell genes between the LSIL/HSIL and controls. However, a significant difference in methylation levels was found between HSIL cases and controls when considering a combination of viral genes and EPB41L3 (p value = .0001). HPV-vaccinated women with HSIL had HPV infections with uncommon HPV types that very rarely cause cancer and displayed low methylation levels. Further investigation is warranted to understand the likely regressive nature of HSIL among HPV-vaccinated women and its implications for management., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Objective: To determine the prevalence of genital infections (GIs), including sexual transmitted STIs: Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, Trichomonas vaginalis, and opportunistic pathogens that generally do not cause STIs, non-classic STI: Ureaplasma urealyticum, Ureaplasma parvum and Mycoplasma hominis, in women with high-risk oncogenic human papillomavirus (hr-HPV) infection and their association with cervical lesions., Methods: A cross-sectional study was carried out including 231 hr-HPV positive women. Of these, 46 has histologically confirmed cervical intraepithelial neoplasia 3 (CIN3) or more (including CIN3 and cervical cancer lesions-CIN3+). GIs were detected by multiplex real time PCR. Odds ratios (OR) were estimated to explore possible associations between GIs and the presence or absence of CIN3+ lesions. Additionally, we examined associations between sociodemographic, sexual, and clinical characteristics and the presence of GIs., Results: In total, there were 174/231 cases of GIs corresponding to an overall prevalence of 75.3% (95%CI: 69.4-80.4), being non-classic STIs the most common (72.3%) compared to STIs (12.6%). The most prevalent non-classic STI and STI were U. parvum (49.8%) and C. trachomatis (7.4%), respectively. The odds of presenting GIs were 3 times higher in women under 46 years compared to older counterparts (OR: 3.32, 95%CI: 1.74-6.16), and in women with a normal Pap smear with inflammation compared to those without inflammation (OR: 3.31, 95%CI: 1.15-9.77). GIs were equally present in women with and without CIN3+ lesions., Conclusion: We observed an association of GIs with inflammation in the Pap smear, but no association with CIN3+, as some of them are very common and likely part of the normal vaginal flora, suggesting that such infections do not appear to be cofactors in cervical carcinogenesis, although larger prospective studies are needed., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Arévalos et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To assess the knowledge and acceptability of the human papillomavirus (HPV) vaccine and the associated factors among adolescent girls in public primary schools in Dessie Town, South Wollo, Northeast Ethiopia in 2020., Design, Participants and Methods: This was an institutional cross-sectional study conducted from 1 November to 30 November 2020 among 844 adolescent girls. A systematic random sampling method was used to select participants, who completed a pretested, self-administered questionnaire. Data were entered into EpiData V.4.6 and exported to SPSS V.25 for analysis. A binary logistic regression model identified the contributing factors to HPV vaccine knowledge and acceptance. Adjusted OR (AOR) and 95% CI computed at p<0.05 were used to assess significance levels., Main Outcome Measures: The primary outcomes of interest were knowledge and acceptability of the HPV vaccine., Results: The HPV vaccine is known and acceptable to 47% and approximately 43% of the respondents, respectively. Age (AOR=3.51, 95% CI 1.62 to 7.6), father's educational level (AOR=2.62, 95% CI 1.57 to 4.38) and parent-child communication about sex and reproductive health (AOR=1.94, 95% CI 1.36 to 2.76) were associated with knowledge of the HPV vaccine. Acceptance of the HPV vaccine was significantly influenced by fathers' educational level (AOR=1.88, 95% CI:1.02 to 3.29), knowledge of Pap smear tests (AOR=2.54, 95% CI 1.79 to 3.62) and knowledge of the HPV vaccine (AOR=5.30, 95% CI 3.77 to 7.73)., Conclusion: In this study, there was generally good and high acceptance of the HPV vaccine, respectively, compared with a study conducted in Southwest Ethiopia. The study, however, had limitations in terms of recall bias, assessment of coverage/effectiveness over time and generalisability due to the institutional sample used., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: International guidelines recommend cervical screening cessation at age 50 following two consecutive negative screens. However, many women aged 50 and older in low-income and middle-income countries (LMICs) have not had prior opportunity to screen. We examine the prevalence of cervical dysplasia and cervical cancer stage in Botswana women aged 50+ compared with 30-49, stratified by HIV status., Design: Secondary analysis of data from two prospective cohort studies., Setting: The screening cohort was recruited at health facilities in South East District. The cancer cohort was recruited from the primary public tertiary referral hospital and a private hospital in Gaborone, Botswana., Participants: The screening cohort included 2570 women aged 30 and older recruited from February 2021 to August 2022. Screening eligibility included anyone with a cervix and without a prior history of cervical cancer. The cancer cohort included 1520 patients diagnosed with cervical cancer who sought care at the facilities where recruitment took place from January 2015 to December 2022., Primary and Secondary Outcome Measures: The prevalence of cervical intraepithelial neoplasia (CIN)2+ and cancer stage at diagnosis was compared across age groups, stratified by HIV status. Prevalence ratios were calculated for the association between age and CIN2+/CIN3+via log-binomial regression., Results: The prevalence of CIN2+ was similar between 30-49 years old and 50+, both among women with HIV (WWH, 15.9% and 19.3%, respectively) and without HIV (13.3% and 10.4%, respectively). Similar findings were found when CIN3+ was used as the outcome. There were no statistically significant differences in prevalence ratios (PRs) across age groups for CIN2+ (adjusted PR (aPR) WWH 1.1 (95% CI 0.80 to 1.6); aPR HIV- 0.78 (95% CI 0.45 to 1.4) nor CIN3+ (aPR WWH 1.1 (95% CI 0.70 to 1.6); aPR HIV- 0.81 (95% CI 0.40 to 1.7)). Nearly half of cervical cancer diagnoses were made in women 50+; three-quarters of cases in women without HIV were diagnosed at 50+ years., Conclusions: Our findings demonstrate the prevalence of high-grade cervical dysplasia and cervical cancer remains high beyond age 50 in both women with and without HIV in an LMIC context with high HIV prevalence. Screening women 50+ will allow treatment for cervical dysplasia and may provide early diagnosis of curable cervical cancer. These findings support the rapid introduction of high-performance cervical screening to increase access for women 50+., Trial Registration Number: NCT04242823., Competing Interests: Competing interests: RL reports support for present manuscript—NIH NCI 1K08CA271949-01. AM reports support for present manuscript—UM1TR004408 award through Harvard Catalyst. LB-M reports support for attending meetings and/or travel from MSD. PV reports payment or honoraria from Novartis, Roche, MSD; support for attending meetings and/or travel from MSD, Roche. SG reports grants from National Cancer Institute; grants or contracts from Varian Medical Systems; consulting fees from GenesisCare USA, payment or honoraria from Varian Medical Systems; stock or stock options in Harbinger Health. All other authors report no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Cervical cancer (CC) was considered to be the most common gynaecological cancer, with an estimated 342,000 deaths worldwide each year, as the majority of patients were diagnosed at an advanced stage of the disease. The purpose of this study was to evaluate the predictive value of multi-locus methylation assay for the early detection of CC. The cervical exfoliated cell samples from 492 HPV-positive females with cervical lesions were collected and subjected to methylation detection of gene FAM19A4, EPB41L3 and PAX1 after bisulfite conversion. The levels of gene methylation in patients with different severity of cervical lesions were evaluated and compared. The receiver-operating characteristic (ROC) curve was established and efficacy indexes such as sensitivity, specificity and area under the curve (AUC) were calculated to assess the diagnostic value of DNA methylation detection at multiple gene loci for CC. The methylation levels of FAM19A4, EPB41L3 and PAX1 were significantly increased with the grade of cervical squamous intraepithelial lesions. The sensitivities of FAM19A4, EPB41L3 and PAX1 alone for high-grade squamous intraepithelial lesion (HSIL) and CC diagnosis were 84.6%, 86.3% and 88.0%, respectively; when three markers were combined by a logistic regression model, the sensitivity was 88.0%, with a high specificity of 97.7% and AUC of 0.957 (95% CI 0.937-0.977). Methylation status of FAM19A4, EPB41L3 and PAX1 were highly specific and effective for monitoring the progression of cervical lesions and the tri-gene methylation assay could be used as a triage tool for CC early screening., (© 2024. The Author(s).)

Objective: To evaluate the role of being human immunodeficiency virus (HIV) positive for predicting the risk of recurrence in women with a cervical high grade squamous intraepithelial lesion (HSIL) diagnosis., Methods: Retrospective observational case-control study, comprising HIV positive (case) and HIV negative (control) women in a 1:4 ratio. Women assisted by the Erasto Gaertner Hospital, between 2009-2018, with cervical HSIL diagnosis, submitted to treatment by Loop electrosurgical excision procedure (LEEP), and with a minimum follow-up of 18 months, were included. The immunological status, number and time to recurrence were analyzed, with p<0.05 considered significant. In a second analysis, only patients with free margins were evaluated., Results: The sample consisted of 320 women (64 cases and 256 controls). Presence of HIV, CD4 levels <200 and detectable viral load (CV) were associated with high risk of recurrence, with odds ratio (OR) of 5.4 (p<0.001/95CI:2.8-10); 3.6 (p<0.001 /IC95:0.6-21.1) and 1.8 (p=0.039 /IC95:0.3-9.3), respectively. In the sample with free margins (n=271), this risk was also higher among seropositive patients, with OR 4.18 (p=0.001/95CI:1.8-9.2)., Conclusion: HIV is an independent risk factor for cervical HSIL recurrence and reduced disease-free survival time. Glandular involvement, compromised margins, undetectable CV and CD4<200 also increase the risk of relapse., Competing Interests: Conflicts to interest: none to declare., (© 2024. Federação Brasileira de Ginecologia e Obstetrícia. All rights reserved.)

Background: Human Papillomavirus (HPV) DNA screening was a crucial element in the fight against cervical cancer and had been adopted in many countries, including China. However, the onset of the COVID-19 pandemic in March 2020 disrupted this program significantly., Methods: The aim of this study is to investigate the prevalence and distribution of HPV genotypes among the population undergoing cervical cancer screening during the pandemic period. From January 2017 to December 2022, Peking Union Medical College Hospital gathered 45,496 cervical swabs from individuals undergoing cervical cancer screening. These samples were analyzed to detect fifteen high-risk HPV (HR-HPV) DNA types and a combination of two low-risk HPV (LR-HPV) types., Results: The study revealed an overall infection rate of 11.24% (5,114/45,496), with 11.06% (5,032/45,496) of individuals infected with HR-HPV. The number of HPV screening patients and the infection rates of HPV, HR-HPV, LR-HPV, multiple genotype HPV (M-HPV), and single genotype HPV (S-HPV) during the pandemic were lower than those observed before the pandemic. Moreover, the age group with the highest percentage of infected individuals was under 45-49 years, with HPV52, HPV58, HPV16, and HPV51 being the most prevalent genotypes. Notably, HPV66 emerged as the fifth most commonly detected genotype during the pandemic. Additionally, among the eleven age groups examined, women under 25 exhibited the highest detection rate, with HPV52 and HPV16 infection rates exceeding those observed in the pre-pandemic period., Conclusions: The findings of this study offer significant insights for shaping HPV prevention strategies and enhancing cervical cancer screening initiatives in China following the epidemic., (© 2024. The Author(s).)

Objectives: The World Health Organization supports both the screen-and-treat (ST) approach and the screen, triage and treat (STT) approach to cervical cancer screening using high-risk human papillomavirus (hrHPV) testing. For Uganda, the sequence of hrHPV-ST and hrHPV-STT could be similar, with visual inspection with acetic acid (VIA) after positive hrHPV tests in both. To consider potential tradeoffs (overtreatment in ST versus missed cancer cases in STT), we compared hrHPV-STT with VIA triage (STT-VIA), and STT with HPV 16/18 genotyping risk stratification, to hrHPV-ST for Uganda, in terms of overtreatment, cervical cancer incidence, and life years, for the general female population of Uganda., Methods: A microsimulation model of cervical cancer was adapted. Incremental benefit-harm ratios of STT were calculated as ratios of prevented overtreatment to reduced life years, and to increased cancer cases. Additional scenarios with 20% difference in intra- and inter-screening follow-up between ST and STT were modeled., Results: Both STT strategies resulted in life year losses on average compared to ST. STT-VIA prevented more overtreatment but led to increased cervical cancer incidence and life year losses. STT-G-VIA resulted in better harm-benefit ratios and additional costs. With better follow-up, STT prevented overtreatment and improved outcomes., Discussion: For Uganda, the STT approach appears preferrable, if the screening sequences of hrHPV-based ST and STT are similar in practice. While VIA triage alone would reduce overtreatment the most, it could also result in more cancer cases. Risk stratification via genotyping could improve STT. Potential follow-up differences and resource availability should be considered by decision-makers when planning Uganda's hrHPV-based screening strategy., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Sultanov et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Persistent infection with high-risk human papillomavirus (HR-HPV) is the main cause of cervical cancer. These chronic infections are characterized by high expression of the HPV E6 and E7 oncogenes and the absence of the L1 and L2 capsid proteins. The regulation of HPV gene expression plays a crucial role in both the viral life cycle and rare oncogenic events. Alternative splicing of HPV mRNA is a key mechanism in post-transcriptional regulation. Through alternative splicing, HPV mRNA is diversified into various splice isoforms with distinct coding potentials, encoding multiple proteins and influencing the expression of HPV genes. The spliced mRNAs derived from a donor splicing site within the E6 ORF and one of the different acceptor sites located in the early mRNA contain E6 truncated mRNAs, named E6*. E6* is one of the extensively studied splicing isoforms. However, the role of E6* proteins in cancer progression remains controversial. Here, we reviewed and compared the alternative splicing events occurring in the genomes of HR-HPV and LR-HPV. Recently, new HPV alternative splicing regulatory proteins have been continuously discovered, and we have updated the regulation of HPV alternative splicing. In addition, we summarized the functions of known splice isoforms from three aspects: anti-tumorigenic, tumorigenic, and other cancer-related functions, including not only E6*, but also E6^E7, E8^E2, and so on. Comprehending their contributions to cancer development enhances insights into the carcinogenic mechanisms of HPV and explores the potential utility of alternative splicing in the diagnosis and treatment of cervical cancer., 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 Wang, Chen, Qu, Gong, Wang, Chen, Zhou, Mo, Zhang, Lin, Bi, Wang, Gu, Li and Sui.)