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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.)

Aim: The importance of human papillomavirus (HPV) co-testing using physician-, self-, and urine-collected samples to predict cervical intraepithelial neoplasia (CIN) grade 1-2 prognoses has not been previously reported. Therefore, this study aimed to investigate outcomes of patients with CIN 1-2 who simultaneously underwent physician-, self-, and urine-collection sampling tests., Methods: This study was conducted in Japan between October 2019 and November 2022 and examined the proportion of cases with CIN 1-2 progressions, the percentage of cases with persistent CIN 1-2, and the outcome differences according to the results of physician-, self-, and urine-sampling tests., Results: There were 105 and 59 CIN 1 and 2 cases, respectively, with progression or persistence in 27 (29.3%) and 21 (50.0%) cases, respectively. The median follow-up was 20 and 12 months, respectively. Progression and persistence of CIN 1 were significantly associated with HPV-positive physician- and self-collected samples. No significant difference was observed between cases with CIN 2 who had HPV-positive and HPV-negative results using any sampling method., Conclusions: Physician- and self-testing for HPV are crucial for predicting disease progression risk in CIN 1 cases. Future research with an extended observation period and consideration of the progression risks is warranted., (© 2024 Japan Society of Obstetrics and Gynecology.)

Introduction: Cervical cancer disproportionately affects those who are underscreened. Human papillomavirus self-collection is a promising tool to expand screening., Objective: Study objectives were to examine 1) factors (provider characteristics and practice type) associated with and 2) attitudes (perceived benefits and concerns) toward using human papillomavirus self-collection for cervical cancer screening in clinical practice., Methods: This study had a mixed method design; prior to regulatory approval of self-collection, we conducted a national survey and interviews of health care providers who perform cervical cancer screening. Quantitative measures included provider and practice characteristics, willingness to recommend, and preferences related to self-collection. Qualitative interviews further elucidated provider perspectives., Results: A total of 1,251 providers completed surveys, and 56 completed interviews. Among survey respondents, 33.4% reported they were likely to offer self-collection, 28.6% were unsure, and 38.0% reported they were unlikely. Most would offer self-collection either in the clinic or at home per patient preference. Male participants, advanced practice providers, internal and family physicians, and those practicing in academic medical center, hospital, or community health settings were more likely than female participants, obstetrician-gynecologist physicians, and those in private practice to indicate they were likely to offer self-collection. Concerns expressed in both surveys and interviews included the adequacy of sample collection and the ability to follow up. Respondents felt that self-collection would be particularly beneficial for those who did not have access to clinician-collected screening, as well as for patients who may have difficulty with pelvic examinations for any reason., Conclusion: Providers considered human papillomavirus self-collection to be a way to expand access for patients with health care barriers and pelvic examination difficulties. They had concerns related to sample adequacy and follow-up after abnormal results., (Copyright © 2024 Jacobs Institute of Women's Health, George Washington University. Published by Elsevier Inc. All rights reserved.)

Purpose: Self-collected testing for human papillomavirus (HPV) is poised to transform cervical cancer screening. Self-tests demonstrate similar accuracy to clinician-collected tests, but for the half a million women served by the Veterans Health Administration (VA) and their clinicians, self-collected cervical cancer screening would be a new practice. We examined VA patient and staff perspectives to inform future implementation., Methods: Semi-structured telephone interviews were conducted between 2021 and 2022 with female veterans receiving VA care (n = 22) and VA women's health nurses, clinicians, and administrators (n = 27). Interviews were audio-recorded and transcribed. Interview questions addressed knowledge and interest, potential advantages or disadvantages, and any questions participants had about self-collected screening. Responses were analyzed using rapid qualitative methods., Main Findings: Five overarching themes were identified. Both patients and staff indicated high interest and enthusiasm for self-collected HPV testing, tempered by questions about test accuracy and logistical considerations. Familiarity with self-testing for other conditions such as colon-cancer screening or COVID made self-collection seem like a simple, convenient option. However, self-testing was not viewed as a good fit for all patients, and concerns about lost opportunities or missed incidental lesions were raised. Patients and staff described challenges with pelvic examinations for patients with past sexual trauma, particularly in the male-dominated VA environment. Pelvic exams can leave patients feeling vulnerable and exposed; self-collected testing was seen as a mechanism for patient empowerment., Principal Conclusions: Veteran patients and VA staff shared common perspectives about potential advantages and disadvantages of self-collected HPV testing. Self-collected HPV testing has the potential to improve trauma-informed preventive health care for veterans., (Published by Elsevier Inc.)

Despite the introduction of Pap testing for screening to prevent cervical cancer in the mid-20th century, cervical cancer remains a common cause of cancer-related mortality and morbidity globally. This is primarily due to differences in access to screening and care between low-income and high-income resource settings, resulting in cervical cancer being one of the cancers with the greatest health disparity. The discovery of human papillomavirus (HPV) as the near-obligate viral cause of cervical cancer can revolutionize how it can be prevented: HPV vaccination against infection for prophylaxis and HPV testing-based screening for the detection and treatment of cervical pre-cancers for interception. As a result of this progress, the World Health Organization has championed the elimination of cervical cancer as a global health problem. However, unless research, investments, and actions are taken to ensure equitable global access to these highly effective preventive interventions, there is a real threat to exacerbating the current health inequities in cervical cancer. In this review, the progress to date and the challenges and opportunities for fulfilling the potential of HPV-targeted prevention for global cervical cancer control are discussed.

Background: Cervical cancer remains a significant public health concern in Europe. Effective introduction and scaling up of human papillomavirus (HPV) detection-based cervical cancer screening (CCS) requires a systematic assessment of health systems capacity. However, there is no validated capacity assessment methodology for CCS programmes, especially in European contexts. Addressing this gap, our study introduces an innovative and adaptable protocol for evaluating the capacity of CCS programmes across varying European health system settings., Methods: Our research team developed a three-step capacity assessment framework, incorporating a health policy review checklist, a facility visit survey, and key informants' interview guide followed by a strengths, weaknesses, opportunities and threats (SWOT) analysis. Piloting this comprehensive approach, we explored the CCS capacity in three countries: Estonia, Portugal and Romania. These countries were selected due to their contrasting healthcare structures and resources, providing a diverse overview of the European context., Results: Conducted over a period of 9 months, the capacity assessment covered multiple resources, 27 screening centres, 16 colposcopy and treatment centres and 15 key informant interviews. Our analysis highlighted both shared and country-specific challenges. A key common issue was ensuring high compliance to follow-up and management of screen-positive women. We identified considerable heterogeneity in resources and organization across the three countries, underscoring the need for tailored, rather than one-size-fits-all, solutions., Conclusions: Our study's novelty lies in the successful development of this capacity assessment methodology implementable within a relatively short time frame, proving its feasibility for use in various contexts and countries. The resulting set of materials, adaptable to different cancer types, is a ready-to-use toolkit to improve cancer screening processes and outcomes. This research marks a significant stride towards comprehensive capacity assessment for CCS programmes in Europe. Future directions include deploying these tools in other countries and cancer types, thereby contributing to the global fight against cancer., (© 2024. The Author(s).)

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

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

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

Cervical cancer (CC) is the fourth most common cancer among female patients. The primary cause of all types of cervical cancer is human papillomavirus (HPV), which was projected to account for 5,70,000 reported cases in 2018. Two HPV strains (16 and 18) account for 70 % of cervical abnormalities and precancerous cervical cancers. CC is one of the main causes of the 17 % cancer-related death rate among Indian women between the ages of 30 and 69 is CC. The side effects of the currently approved treatments for cervical cancer could endanger the lives of women affected by the illness. Thus, probiotics may be extremely important in the management of CC. Numerous studies on probiotics and their potential for use in cancer diagnosis, prevention, and treatment have been conducted. This review describes the enhancement of the immune system, promotion of a balanced vaginal microbiome, and decreased risk of secondary infections, which have anti-inflammatory effects on the body. Probiotics have the potential to reduce inflammation, thereby adversely affecting cancer cell growth and metastasis. During the course of antibiotic therapy, they support a balanced vaginal microbiome. Oncogenic virus inactivation is possible with probiotic strains. In postmenopausal women, the use of vaginal probiotics helps lessen menopausal symptoms caused by Genitourinary Syndrome of Menopause (GSM). The antitumor effects of other medications can be enhanced by them as potential agents, because they can both promote the growth of beneficial bacteria and reduce the quantity of potentially harmful bacteria. The development of tumors and the proliferation of cancer cells may be indirectly affected by the restoration of the microbial balance. Probiotics may be able to prevent and treat cervical cancer, as they seem to have anticancer properties. To identify probiotics with anticancer qualities that can supplement and possibly even replace traditional cancer treatments, further investigation is required, including carefully planned clinical trials., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could influence the work reported in this study., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Human papillomavirus (HPV) is the cause of almost all cases of cervical cancer, a disease that kills some 340,000 women per year. The timeline from initial infection with HPV to the onset of invasive cervical cancer spans decades, and observational studies of this process are limited to settings in which treatment of precancerous lesions was withheld or inadequate. Such studies have been critical for understanding the natural history of HPV. Modeling can shed additional insight on the natural history of HPV, especially across geographical settings with varying prevalence of factors known to affect the host-side immune response to HPV, such as HIV and tobacco use. In this study, we create models for the 30 most populous countries in Sub-Saharan Africa, each with country-specific demographic, and behavioral inputs. We found that it was not possible to fit the data if we assumed that the natural history parameters were exactly identical for all countries, even after accounting for demographic and behavioral differences, but that we could achieve a good fit with the addition of a single immunocompetence parameter for each country. Our results indicate that variation in host immune responses may play a role in explaining the differences in the burden of cervical cancer between countries, which in turn implies a greater need for more geographically diverse data collection to understand the natural history of HPV., (© 2024. The Author(s).)

The Cervical Screening Cohort enrols women screened for human papillomavirus (HPV) and cervical abnormalities within the capital region of Sweden from the organised screening program and the non-organised testing of cervical samples. The cohort started in 2011 and has enrolled more than 670,000 women, contributing with more than 1.2 million biobanked samples. The cohort is systematically updated with individual-level data from the Swedish National Cervical Screening Registry (NKCx). Key variables include birthdate, sampling date, cytological, histopathological and HPV analysis results, and invitation history. Each sampling and subsequent clinical follow-up is sequentially registered, allowing for longitudinal analyses of screening results and associated results of the clinical workup. The cohort is ideal for longitudinal, long-term follow-up studies due to its validated documentation and registry-derived information. From the data, it is possible to penetrate important human health mechanisms. The data are available as open-data and GDPR-compliant. Samples are available after getting the required permissions. Results will help researchers understand factors that increase cancer risk and other diseases., (© 2024. The Author(s).)

Loss to follow-up (LTFU) within cervical screening programmes can result in missed clinically relevant lesions, potentially reducing programme effectiveness. To examine the health impact of losing women during the screening process, we determined the proportion of women LTFU per step of the Dutch hrHPV-based screening programme. We then determined the probability of being LTFU by age, screening history and sampling method (self- or clinician-sampled) using logistic regression analysis. Finally, we estimated the number of missed CIN2+/3+ lesions per LTFU moment by using the CIN-risk in women compliant with follow-up. Data from the Dutch nationwide pathology databank (Palga) was used. Women eligible for screening in 2017 and 2018 were included (N = 840,428). For clinician collected (CC) samples, the highest proportion LTFU was found following 'referral advice for colposcopy' (5.5% after indirect referral; 3.8% after direct referral). For self-sampling, the highest proportions LTFU were found following the advice for repeat cytology (13.6%) and after referral advice for colposcopy (8.2% after indirect referral; 4.3% after direct referral). Self-sampling users and women with no screening history had a higher LTFU-risk (OR: 3.87, CI: 3.55-4.23; OR: 1.39, CI: 1.20-1.61) compared to women that used CC sampling and women that have been screened before, respectively. Of all women LTFU in 2017/18, the total number of potentially missed CIN2+ was 844 (21% of women LTFU). Most lesions were missed after 'direct referral for colposcopy' (N = 462, 11.5% of women LTFU). So, this indicates a gap between the screening programme and clinical care which requires further attention, by improving monitoring of patients after referral., (© 2024 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

The study sought to systematically compare the expression of molecular markers in benign cutaneous lesions and squamous cell cervical carcinoma associated with HPV infection to better understand the pathophysiological mechanisms involved in HPV-related lesions and their progression to malignancy. We included 200 patients recruited from a gynecological clinic divided into two groups: 100 patients with positive HPV tests presenting with cutaneous lesions and 100 patients diagnosed with squamous cell cervical carcinoma and testing positive for HPV. The participants were selected to ensure diverse ethnic and demographic representation. The study utilized different statistical analyses, including Chi-square tests to assess associations between categorical variables and logistic regression to evaluate factors influencing lesion progression and compare marker expressions across different lesion types. The results indicated significant differences in the expression of specific molecular markers between cutaneous lesions and cervical carcinomas, highlighting distinct molecular pathways involved in HPV-related lesion development. Notably, markers such as p16, p53, and E-cadherin showed varying expression, suggesting their potential role in distinguishing between benign and malignant lesions. The findings emphasize the significance of molecular marker profiling in improving diagnostic and therapeutic strategies for HPV-related lesions. The differential expression of molecular markers can offer valuable insights into the pathogenesis of HPV-induced lesions and help develop targeted interventions to prevent malignant transformation. Further research is necessary to validate these markers in larger cohorts and diverse populations., Competing Interests: The authors declare no conflict of interest., (© 2024 by the authors.)

Purpose: The aim of this study is to reveal female university students' knowledge and perceptions about cervical cancer (CC) and human papillomavirus (HPV), and relationship with e-health literacy (e-HL). It also aims to determine the predictors affecting CC and HPV. Methods: A cross-sectional study was conducted with 589 female university students in Türkiye. Data were collected using a "Cervical Cancer and HPV Awareness Questionnaire" and an "E-health Literacy Scale (e-HLS)." Analysis involved Pearson correlation analysis, Independent Sample t -test, one-way analysis of variance, and Linear Regression analysis. Results: Results indicate that female students exhibited a low level of knowledge and perception about CC and HPV. Only 2.90% of students reported being vaccinated, while 39.90% had sexual experience. Higher knowledge levels were observed among married individuals, those familiar with HPV and the HPV vaccine, those who had undergone Pap smear tests, sexually active individuals, and consistent condom users. e-HL had a positive impact on knowledge and perceived threat about CC and HPV. The affecting predictors for knowledge about CC and HPV were found to be e-HLS (β = 0.911), having prior knowledge of HPV (β = 0.201), and being aware of the HPV vaccine (β = 0.172). In terms of perceived threat, the affecting predictors were e-HLS (β = 0.207), having heard of HPV (β = 0.101), and having knowledge of the HPV vaccine (β = 0.092). Conclusion: e-HL emerged as a crucial predictor positively influencing knowledge and perceptions about CC and HPV. This suggests the potential for organizing digital health campaigns to enhance awareness and understanding of CC and HPV.

Objective: To assess the costs and benefits of two algorithms for cervical cancer screening in Belgium (1) high-risk human papillomavirus (HR-HPV) primary screening and (2) HR-HPV and liquid-based cytology (LBC) co-testing., Methods: A decision tree was adapted from published work and parameterised using HORIZON study data and Belgian cost and population data. The theoretical model represents two different screening algorithms for a cohort of 577 846 women aged 25-64 attending routine cervical screening. Scenario analyses were used to explore the impact of including vaccinated women and alternative pricing approaches. Uncertainty analyses were conducted., Results: The cost per woman screened was €113.50 for HR-HPV primary screening and €101.70 for co-testing, representing a total cost of €65 588 573 and €58 775 083, respectively, for the cohort; a 10% difference. For one screening cycle, compared to HR-HPV primary, co-testing resulted in 13 173 more colposcopies, 67 731 more HR-HPV tests and 477 020 more LBC tests. Co-testing identified 2351 more CIN2+ cases per year (27% more than HR-HPV primary) and 1602 more CIN3+ cases (24% more than HR-HPV primary) than HR-HPV primary., Conclusion: In Belgium, a co-testing algorithm could increase cervical pre-cancer detection rates compared to HR-HPV primary. Co-testing would cost less than HR-HPV primary if the cost of the HPV test and LBC were cost-neutral compared to the current cost of LBC screening but would cost more if the cost per HPV test and LBC were the same in both co-testing and HR-HPV primary strategies., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

The aim of this study was to analyze the association between vaginal microbiota, carbonic anhydrase IX (CAIX) and histological findings of cervical intraepithelial neoplasia (CIN). The study included 132 females, among them 66 were diagnosed with high-grade intraepithelial lesion (CIN2, CIN3, and cancer), 14 with low-grade disease, and 52 assigned to the control group. An interview focused on the behavior risk factors, together with vaginal fluid pH measurement, wet mount microscopy, detection of Chlamydia trachomatis, and Trichomonas vaginalis were performed. After colposcopy, high-grade abnormalities were detected via direct biopsies and treated with conization procedure. Conuses were immuno-stained with CAIX antibody. The histological findings were CIN1 (n = 14), and CIN2+ (included CIN2 (n = 10), CIN3 (n = 49), and cancer (n = 7; squamous cell carcinomas)). Prevalence of bacterial vaginosis (BV) was similar between the groups. Moderate or severe aerobic vaginitis (msAV) was diagnosed more often among CIN2+ (53.0%) than CIN1 (21.4%). Moderate or strong immunostaining of CAIX (msCAIX) was not detected among CIN1 cases. Thus, msAV was prevalent in CAIX non-stained group (p = 0.049) among CIN2 patients. Co-location of msAV and msCAIX was found in CIN3. Regression model revealed that msAV associated with high-grade cervical intraepithelial neoplasia independently from smoking and the number of partners., (© 2024. The Author(s).)

Background: In order for low and middle income countries (LMIC) to transition to Human Papilloma Virus (HPV) test based cervical cancer screening, a greater understanding of how to implement these evidence based interventions (EBI) among vulnerable populations is needed. This paper documents outcomes of an implementation research on HPV screening among women from tribal, rural, urban slum settings in India., Methods: A mixed-method, pragmatic, quasi-experimental trial design was used. HPV screening on self-collected cervical samples was offered to women aged 30-60 years. Implementation strategies were 1) Assessment of contextual factors using both qualitative and quantitative methods like key informant interviews (KII), focus group discussions (FGDs), pre-post population sample surveys, capacity assessment of participating departments 2) enhancing provider capacity through training workshops, access to HPV testing facility, colposcopy, thermal ablation/cryotherapy at the primary health care centers 3) community engagement, counselling for self-sampling and triage process by frontline health care workers (HCWs). Outcomes were assessed using the RE-AIM (Reach, Effectiveness, adoption, implementation, maintenance) framework., Results: Screening rate in 8 months' of study was 31.0%, 26.7%, 32.9%, prevalence of oncogenic HPV was 12.1%, 3.1%, 5.5%, compliance to triage was 53.6%, 45.5%, 84.6% in tribal, urban slum, rural sites respectively. Pre-cancer among triage compliant HPV positive women was 13.6% in tribal, 4% in rural and 0% among urban slum women. Unique challenges faced in the tribal setting led to programme adaptations like increasing honoraria of community health workers for late-evening work and recalling HPV positive women for colposcopy by nurses, thermal ablation by gynaecologist at the outreach camp site., Conclusions: Self-collection of samples combined with HCW led community engagement activities, flexible triage processes and strengthening of health system showed an acceptable screening rate and better compliance to triage, highlighting the importance of identifying the barriers and developing strategies suitable for the setting., Trial Registration: CTRI/2021/09/036130., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Oommen 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.)

Purpose: This study aimed to explore the clinical characteristics and risk factors associated with cervical intraepithelial neoplasia (CIN) when coexisting with vaginal intraepithelial neoplasia (VAIN)., Methods: We analyzed the clinical data of 212 patients diagnosed with CIN, including 50 patients with concurrent VAIN. The groups were compared to identify distinct clinical features and independent risk factors for the co-occurrence of CIN and VAIN, using logistic regression analysis., Results: Patients with both CIN and VAIN had a median age of 57, significantly older than the 41-year median age of patients with CIN only (P < 0.05). A higher prevalence of HPV infection (98.0%) was observed in the CIN and VAIN group, with a notable rate of multiple HPV infections (67.3%) compared to the CIN-only group (P < 0.05). Educational levels were significantly lower in the combined CIN and VAIN group (P < 0.05). HPV16, 33, and 52 were identified as significant types for single and multiple infections. Multivariate analysis confirmed age as an independent risk factor for CIN with VAIN (P < 0.05). VAIN3 patients were more likely to exhibit HSIL and ASC-H, whereas VAIN1 cases tended to correspond with ASCUS and LSIL diagnoses., Conclusion: The co-occurrence of CIN and VAIN is significantly influenced by patient age and educational level. The findings advocate for more diligent vaginal examination during colposcopy in older patients, particularly those with multiple HPV infections and cytological abnormalities, to enhance the early detection of vaginal lesions and prevent missed diagnoses and treatments. Additionally, the high prevalence of HPV infection, especially with certain types, underscores the importance of HPV monitoring in this patient population., (© 2024. The Author(s).)

Source Citation: Winer RL, Lin J, Anderson ML, et al. Strategies to increase cervical cancer screening with mailed human papillomavirus self-sampling kits: a randomized clinical trial. JAMA. 2023;330:1971-1981. 38015219., Competing Interests: Disclosures: The commentator has reported no disclosures of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=J24-0019.

Objectives: The Enduring Consensus Cervical Cancer Screening and Management Guidelines Committee developed recommendations for dual stain (DS) testing with CINtec PLUS Cytology for use of DS to triage high-risk human papillomavirus (HPV)-positive results., Methods: Risks of cervical intraepithelial neoplasia grade 3 or worse were calculated according to DS results among individuals testing HPV-positive using data from the Kaiser Permanente Northern California cohort and the STudying Risk to Improve DisparitiES study in Mississippi. Management recommendations were based on clinical action thresholds developed for the 2019 American Society for Colposcopy and Cervical Pathology Risk-Based Management Consensus Guidelines. Resource usage metrics were calculated to support decision-making. Risk estimates in relation to clinical action thresholds were reviewed and used as the basis for draft recommendations. After an open comment period, recommendations were finalized and ratified through a vote by the Consensus Stakeholder Group., Results: For triage of positive HPV results from screening with primary HPV testing (with or without genotyping) or with cytology cotesting, colposcopy is recommended for individuals testing DS-positive. One-year follow-up with HPV-based testing is recommended for individuals testing DS-negative, except for HPV16- and HPV18-positive results, or high-grade cytology in cotesting, where immediate colposcopy referral is recommended. Risk estimates were similar between the Kaiser Permanente Northern California and STudying Risk to Improve DisparitiES populations. In general, resource usage metrics suggest that compared with cytology, DS requires fewer colposcopies and detects cervical intraepithelial neoplasia grade 3 or worse earlier., Conclusions: Dual stain testing with CINtec PLUS Cytology is acceptable for triage of HPV-positive test results. Risk estimates are portable across different populations., Competing Interests: N.B. has served as a consultant for Dysis. M.E. has served as a consultant for Papivax, Merck, BD, and PDS. R.G. has served as a consultant for Inovio. D.H. has served as a consultant for Roche. W.H. has served as a consultant for Roche, SeeGene, and AstraZeneca. R.N. has participated in an educational meeting supported by Roche. D.C. has received stipends from ABOG and Medscape and is currently receiving project funding from ACOG. The other authors have declared they have no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the ASCCP.)

Objective: To date, no data supports the execution of vaccination after hysterectomy for high-grade cervical intraepithelial neoplasia (CIN2+) and early-stage cervical cancer. We aim to evaluate the potential effect of vaccination after hysterectomy for high-grade cervical intraepithelial neoplasia and early-stage cervical cancer., Methods: This is a multi-center retrospective study evaluating data of women who develop lower genital tract dysplasia (including anal, vulvar and vaginal intra-epithelial neoplasia) after having hysterectomy for CIN2+ and FIGO stage IA1- IB1 cervical cancer., Results: Overall, charts for 77 patients who developed lower genital tract dysplasia were collected. The study population included 62 (80.5%) and 15 (19.5%) patients with CIN2+ and early-stage cervical cancer, respectively. The median (range) time between hysterectomy and diagnosis of develop lower genital tract dysplasia was 38 (range, 14-62) months. HPV types covered by the nonavalent HPV vaccination would potentially cover 94.8% of the development of lower genital tract dysplasia. Restricting the analysis to the 18 patients with available HPV data at the time of hysterectomy, the beneficial effect of nonvalent vaccination was 89%. However, considering that patients with persistent HPV types (with the same HPV types at the time of hysterectomy and who developed lower genital tract dysplasia) would not benefit from vaccination, we estimated the potential protective effect of vaccination to be 67% (12 out of 18 patients; four patients had a persistent infection for the same HPV type(s))., Conclusions: Our retrospective analysis supported the adoption of HPV vaccination in patients having treatment for HPV-related disease. Even in the absence of the uterine cervix, HPV vaccination would protect against develop lower genital tract dysplasia. Further prospective studies have to confirm our preliminary research., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: This study aimed to investigate the characteristics and screening history of vaginal intraepithelial neoplasia (VaIN) or vaginal cancer and compare the sensitivity of cytology and human papillomavirus (HPV) tests on the cervix against vaginal and cervical high-grade squamous intraepithelial lesion or cancer., Methods: This study included patients who underwent colposcopy-directed biopsy and were diagnosed with VaIN or vaginal cancer from February 2013 to November 2022. Clinical information was obtained from the medical records of the department. Statistical analysis was performed on SPSS 26.0 (IBM Corp, Armonk, NY) using t test, chi-square, and Fisher exact tests., Results: A total of 1,166 patients were included in this study. The median age of VaIN2+ patients was 50.5 years, whereas VaIN1 reported a median age of 42.1 years old, p < .001. This study reported that VaIN was significantly and positively correlated with cervical lesions (r = 0.244). The high-risk HPV (hr-HPV) detection rate was 88.2% (858/973) in VaIN and 95.2% in VaIN2+. Human papillomavirus 16 was the most prevalent HPV type in VaIN2+, which accounted for 54.9%, followed by HPV58 (19.5%), HPV52 (15.2%), HPV51 (12.2%), and HPV18 (11.0%). The sensitivity of hr-HPV and cytology tests on the cervix for detecting VaIN2+ was 94.7% and 83.4%, respectively. Both tests were not significantly different from detecting cervical intraepithelial neoplasia 2+., Conclusions: Human papillomavirus 16 is the dominant HPV type in vaginal precancer lesions. Cervical cancer screening has similar sensitivity for VaIN2+ as for cervical intraepithelial neoplasia 2+, with hr-HPV testing showing higher sensitivity than cytology., Competing Interests: The authors have declared they have no conflicts of interest., (Copyright © 2023, ASCCP.)

Purpose: Persistent high-risk HPV infection is associated with an elevated risk for prevalent CIN II + despite normal cytology (NILM). Our study aims to evaluate the clinical relevance of a persistent high-risk HPV infection without cytologic changes in women aged ≥ 65 and to determine the role of colposcopy for triage in these cases., Methods: 211 patients aged ≥ 65 with persistent HPV infection and normal cytology (NILM) who presented for colposcopy at five certified centers between January 2021 and April 2022 were included in the study. Colposcopic findings, HPV subtypes, when available, histology and p16/Ki67 staining were assessed as well as individual risk factors such as smoking and previous HPV-related surgery., Results: 87.7% (185/211) of the included women had a type 3 transformation zone. In 83.4% (176/211), a biopsy was taken [thereof 163 endocervical curettages (ECC)]. In 35/211 women (16.6%), sampling was not possible during colposcopy due to an inaccessible cervix, pain during examination or obliteration of the cervical canal. Out of these, 6 women received a diagnostic excision. CIN II + was detected in 10.6% of all histologies (excisional or biopsy) (20/182). 50% of the women with a CIN II + where HPV 16 positive. Taking only the women diagnosed with CIN III or AIS into account, (n = 12) 75% were HPV 16 positive. Interestingly, 80% of the women with CIN II + had an abnormal cytology when repeatedly taken during colposcopy, vice versa an endocervical lesion was diagnosed in 53% of women with abnormal repeat cytology (27/51)., Conclusion: The prevalence of CIN II + in women is ≥ 65 with persistent hr HPV infection but NILM cytology is similar to that in younger women. However, more than 85% of the women have a type 3 transformation zone. Colposcopy is, therefore, not helpful to diagnose the women who need treatment in this age group., (© 2023. The Author(s).)

Objective: There is evidence in Germany that half of the cervical cancer (CC) cases had undergone screening frequently in the decade preceding their diagnosis, signaling cytology quality issues. This study investigates routine smear assessment accuracy in Germany., Methods: Within a population-based case-control study in 9 German states, we recruited cases (women with a histologically confirmed diagnosis of CC) and population controls (women with no history of CC or hysterectomy). Two independent expert cytologists audited Pap smears taken within the 10 years preceding CC diagnosis (cases)/study entry (controls). We report the prevalence of positive results, as well as routine assessment's accuracy, as sensitivity, specificity, false-positive and false-negative rates along with 95% confidence intervals (95% CI). We also examined cases' smear history, to investigate possible false-positive recurrence., Results: We audited 1632 smears of 392 women (18.9% cases, 81.1% controls). In the routine assessment, the overall prevalence of positive results was 4.5% (29.0% among cases). According to the expert audit, the overall prevalence of positive results was 7.7% (40.8% among cases). When restricting analyses to the 3 years preceding diagnosis/study entry, this prevalence increased to 11.9% overall (61.4% among cases). The overall sensitivity of the routine assessment was 54.9% (66.8% for cases)., Conclusion: As cytology remains an important part of CC screening, quality issues must be urgently addressed in Germany. Shifting to objective methods such as primary high-risk HPV screening followed by triaging may help CC elimination in Germany., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Olaf Schoffer worked as a consultant for Novartis. Hans Ikenberg reports co-ownership of a laboratory for cytology and molecular diagnostics and financial support from Roche Diagnostics and Hologic Deutschland GmbH. All remaining authors have declared no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To determine whether knowledge of cytology affects the colposcopist's diagnostic accuracy in the identification of cervical intraepithelial neoplasia grade 2 and worse (≥ CIN2)., Method: In this cross-over study, healthcare professionals interpreted colposcopy images from 80 patient cases with known histological diagnoses. For each case, 2 images taken with a colposcope were provided (native and after acetic acid application). Inclusion criteria consisted of women with a transformation zone type 1 or 2, who had both a cytological and histological diagnosis. Cases were distributed across two online surveys, one including and one omitting the cytology. A wash-out period of six weeks between surveys was implemented. Colposcopists were asked to give their diagnosis for each case as < CIN2 or ≥ CIN2 on both assessments. Statistical analysis was conducted to compare the two interpretations., Results: Knowledge of cytology significantly improved the sensitivity when interpreting colposcopic images, from 51.1% [95%CI: 39.3 to 62.8] to 63.7% [95%CI: 52.1 to 73.9] and improved the specificity from 63.5% [95%CI: 52.3 to 73.5] to 76.6% [95%CI: 67.2 to 84.0]. Sensitivity was higher by 38.6% when a high-grade cytology (ASC-H, HSIL, AGC) was communicated compared to a low-grade cytology (inflammation, ASC-US, LSIL). Specificity was higher by 31% when a low-grade cytology was communicated compared to a high-grade., Conclusions: Our data suggests that knowledge of cytology increases sensitivity and specificity for diagnosis of ≥ CIN2 lesions at colposcopy. Association between cytology and histology may have contributed to the findings., (© 2024. The Author(s).)

Background: Understanding the natural history of human papillomavirus (HPV) infections is essential to cervical cancer prevention planning. We estimated HPV type-specific infection detection and clearance in young women., Methods: The HPV Infection and Transmission among Couples through Heterosexual activity (HITCH) study is a prospective cohort of 502 college-age women who recently initiated a heterosexual relationship. We tested vaginal samples collected at 6 clinical visits over 24 months for 36 HPV types. Using rates and Kaplan-Meier analysis, we estimated time-to-event statistics with 95% confidence intervals (CIs) for detection of incident infections and clearance of incident and present-at-baseline infections (separately). We conducted analyses at the woman- and HPV-levels, with HPV types grouped by phylogenetic relatedness., Results: By 24 months, we detected incident infections in 40.4% (CI, 33.4%-48.4%) of women. Incident subgenus 1 (43.4; CI, 33.6-56.4), 2 (47.1; CI, 39.9-55.5), and 3 (46.6; CI, 37.7-57.7) infections cleared at similar rates per 1000 infection-months. We observed similar homogeny in HPV-level clearance rates among present-at-baseline infections., Conclusions: Our analyses provide type-specific infection natural history estimates for cervical cancer prevention planning. HPV-level analyses did not clearly indicate that high oncogenic risk subgenus 2 infections persist longer than their low oncogenic risk subgenera 1 and 3 counterparts., Competing Interests: Potential conflicts of interest. M. Z. and E. L. F. hold a patent related to the discovery “DNA methylation markers for early detection of cervical cancer,” registered at the Office of Innovation and Partnerships, McGill University, Montréal, Québec, Canada, October 2018. A provisional utility patent application before the United States Patent and Trademark Office was also filed (November 2018) and a patent cooperation treaty application (PCT/IB2020/050885), filed in February 2020, has been published (No. WO 2020/115728; June 2020). E. L. F. reports grants and personal fees from Merck outside of the submitted work. F. C. reports grants from Réseau FRQS-SIDA during the conduct of the study, and grants to his institution for HPV-related work from Merck Sharp and Dome, Roche Diagnostics, and Becton Dickinson outside of the submitted work. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

This study assessed the accuracy of high-risk human papillomavirus testing of BD Onclarity HPV (Onclarity) assay on vaginal self-collected FLOQSwab versus cervical samples to ensure similar accuracy to detect cervical intraepithelial neoplasia. Testing was performed on two automated platforms, BD Viper LT and BD COR, to evaluate the effect of machine and using two vaginal self-samples to analyze the influence of collection, transport, and freezing-unfreezing on the results. A cervical sample and two self-samples were collected from 300 women. The first collected vaginal and the cervical sample were tested on BD Viper LT, and the second swab was frozen and subsequently tested on both automated systems. Test results on vaginal and cervical specimens were considered the index and comparator, respectively; colposcopy and histology were reference standards. Relative sensitivity for ≥CIN2 on vaginal samples analyzed versus the cervical sample was 1.01 (0.97-1.06), 1.01 (0.97-1.06), and 1.00 (0.95-1.05), for the first, second self-collected sample tested on BD VIPER LT, and second self-collected sample tested on BD COR, respectively. Relative specificity was 0.83 (0.73-0.94), 0.76 (0.67-0.87), and 0.82 (0.73-0.92) using the three different workflows. Cut-off optimization for human papillomavirus (HPV) positivity defined at Ct ≤38.3 for HPV16, ≤ 34.2 for HPV18, and ≤31.5 for all other types showed an increased relative specificity with similar sensitivity. No significant difference was observed between self-samples tested with the two platforms and between first- and second-collected swabs. Onclarity assay on FLOQSwab using both platforms showed similar sensitivity but lower specificity to detect ≥CIN2 compared to cervical samples. By cut-off optimization, non-inferior specificity could be reached., Importance: Human papillomavirus (HPV) testing on self-collected vaginal samples has been shown to improve women's participation to cervical cancer screening programs, particularly in regions with limited access to health care. Nevertheless, the introduction of self-sampling in cervical cancer screening programs requires prior clinical validation of the HPV assay in combination with a self-sample collection device, including also the laboratory workflow and automation required for high-throughput testing in screening. In this study, the performance of BD Onclarity HPV on FLOQSwab-collected vaginal self-samples has been compared to clinician-taken liquid-based cytology samples, to detect high-grade cervical intraepithelial neoplasia using two high-throughput platforms, BD Viper LT and BD COR. The study findings have shown a similar performance of BD Onclarity on testing self-collected samples, confirming the validation of the proposed pre-analytical and analytical protocols for their use in cervical cancer screening programs based on self-collected vaginal samples., Competing Interests: The Extended VALHUDES is a researcher-induced study designed by the University of Milano-Bicocca (Study Coordinating Centre, Monza, Italy), Sciensano (Statistical Study Report, Bruxelles, Belgium), IEO (Istituto Europeo di Oncologia, Milan, Italy), University of Sassari (Sassari, Italy), U.O. Coordinamento Consultori Familiari, ASSL Sassari - ATS Sardegna (Sassari, Italy) and Molecular Pathology Laboratory (MPL), Department of Pathology (Hvidovre Hospital, Denmark). Manufacturers of HPV assays and devices (BD Diagnostics, Sparks, MD, USA and Copan Italia Spa, Brescia, Italy) participated in the Extended VALHUDES framework contributing financial support and equipment for laboratory testing and statistical analysis under the condition of accepting independent publication of results. The study group received free vaginal self-sample collection devices from Copan Italia Spa (Brescia, Italy) and free BD Onclarity HPV assay from (BD Diagnostics, Sparks, MD, USA). J.B. has received honoraria for lectures or advisory board activity from Roche Molecular Systems, BD Diagnostics, and MSD. C.E.C. has received research support and/or honoraria from BD Diagnostics, Seegene, Arrows Diagnostics, Copan, GeneFirst and Hiantis. M.M., A.L., H.P., A.D.I., F.P., A.F.P., and R.P. declare no conflict of interest.

Introduction: Self-sampling for human papillomavirus testing is increasingly recognized as a strategy to expand cervical cancer screening access and utilization. Acceptability is a key determinant of uptake. This study assesses the acceptability of and experiences with mailed self-sampling kits for human papillomavirus testing among underscreened patients in a safety net health system., Methods: A nested telephone survey was administered between 2021 and 2023 to a sample (n=272) of the 2,268 participants enrolled in the Prospective Evaluation of Self-Testing to Increase Screening trial. Trial participants include patients of a safety net health system aged 30-65 years who were not up to date on screening. Participants were asked about barriers to provider-performed screening. Kit users and nonusers were asked about their experiences., Results: Prevalent barriers to provider-performed screening included perceived discomfort of pelvic examination (69.4%), being uncomfortable with male providers (65.4%), and embarrassment (57.0%). Among participants who reported using the mailed kit (n=164), most reported good experiences (84.8%). Most reported self-sampling as more/equally convenient (89.0%), less/equally embarrassing (99.4%), and less/equally stressful (95.7%) than provider-performed screening. Among kit nonusers (n=43), reasons for not using the kit included forgetting about it (76.7%), preferring provider-performed screening (76.7%), and fearing cancer (67.4%)., Conclusions: Prospective Evaluation of Self-Testing to Increase Screening trial participants generally had a positive experience with self-sampling for human papillomavirus testing. Increased comfort and reduced embarrassment/anxiety with self-sampling are relevant attributes because these were the most prevalent reported barriers to provider-performed screening. High acceptability suggests potentially high uptake when self-sampling for human papillomavirus testing receives regulatory approval and is available in safety net health systems., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background/aim: The global impact of the COVID-19 pandemic resulted in disruptions to healthcare systems throughout the world. The numbers of cytology examinations, human papillomavirus (HPV) tests, and women referred for colposcopy decreased in many countries. There have been no reports on cervical cancer screening in Germany. This study aimed to describe changes in the numbers of colposcopies, cytology examinations, HPV tests, and histological results during the pandemic compared to the pre-pandemic years in order to evaluate the impact of the COVID-19 pandemic on cervical cancer screening., Patients and Methods: The numbers of colposcopies, cytology examinations, HPV tests, and histologic results were analyzed retrospectively for the period January 2018 to December 2022. The 2 years period before the pandemic (2018 and 2019) were compared with the 3 years period of the pandemic (2020-2022)., Results: In total, 6,518 colposcopies were performed in 5,579 women. The numbers of colposcopies, cytology examinations, and high-risk HPV (hrHPV) tests increased during the pandemic years. The number of biopsies per year taken was stable (range=450-554). The relative numbers of cervical intraepithelial neoplasia (CIN) III/HSIL findings were stable, while the numbers of cervical cancers identified increased slightly from 15 (6.6%) in 2018 to 22 (7.4%) in 2022., Conclusion: Increases in numbers of women examined and colposcopies were observed in the years 2021 and 2022 during the pandemic, in comparison to the preceding years. These also led to increases in the figures for cytology, hrHPV, histology, and operations. The onset of the pandemic occurred in the same year as a newly organized screening program started in Germany. The increases might therefore be due to the newly organized screening system., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The Human Papillomavirus (HPV) infection is responsible for more than 80% of reported cervical cancer and other virus-associated tumours. Although this global threat can be controlled using effective vaccination strategies, a growing perturbation of HPV infection is an emerging coinfection likely to increase the severity of the infection in humans. Moreover, these coinfections prolong the HPV infections, thereby risking the chances for oncogenic progression. The present review consolidated the clinically significant microbial coinfections/co-presence associated with HPV and their underlying molecular mechanisms. We discussed the gaps and concerns associated with demography, present vaccination strategies, and other prophylactic limitations. We concluded our review by highlighting the potential clinical as well as emerging computational intervention measures to kerb down HPV-associated severities., (© 2024 John Wiley & Sons Ltd.)

Objective: Denmark went through various COVID-19 pandemic restrictions including periodic lockdowns from March 2020 to January 2022. All cancer screening programs were kept operational, yet access to clinicians for cervical screening was at times limited. We assessed the impact of the pandemic on cervical cancer screening activity in the Capital Region of Denmark., Methods: Cervical screening activity was defined as regular screening by invitation, opportunistic screening, and screening participation by HPV self-sampling. Activity was monitored during and post-pandemic and compared relatively to a 3-year pre-pandemic reference., Results and Conclusions: The activity of cervical cancer screening was initially affected by the pandemic lockdowns, but increased activity during summer 2020 partly compensated this effect. Regular screening activity decreased 8.4% in 2020 and returned to pre-pandemic levels in 2021. During 2022 restrictions were removed and the decrease in activity was recorded to be 2.3%. Opportunistic screening activity was reduced by 14.3% in 2020 and 12.6% in 2021. A continued post-pandemic opportunistic screening activity reduction of 18.5% was observed, possibly related to changed patterns of primary health care use introduced during the pandemic. Screening by HPV self-sampling increased from 17.1% in the pre-pandemic period to 21.2% during the pandemic. Significantly more acceptance was recorded amongst older women (p < 0.0001). This increase mirrors the decrease in total clinician collected sample activity during the pandemic, where an increased reduction by age was observed. Post-pandemic HPV self-sampling participation decreased to 12.8%, possible reflecting a temporarily changed composition and motivation in the group of women invited for self-sampling., Competing Interests: Declaration of competing interest B.T.P, H·P, S.B.·S, E.K.A: Nothing to declare. R.S: Consultant to Merck and Chairman of the Danish Quality Database for Cervical Cancer Screening. J.B. received research funding from BD Diagnostics, GeneFirst, SelfScreen, Qiagen, Seegene and Roche Diagnostics and received honoraria for lectures from BD Diagnostics, MSD and Hologic Ltd. Jesper Bonde is appointed member of the National Danish Cervical Screening Committee by the Danish Health Authority., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: To evaluate the efficacy of Cobas human papillomavirus (HPV) testing to predict cervical intraepithelial neoplasia of grade 2 or higher (CIN2+), Cobas HPV testing results were correlated with follow-up biopsy in patients from Cancer Prevention Center (CPC) and Gynecologic Oncology Clinic (GOC) of The University of Texas MD Anderson Cancer Center., Methods: Institutional data for patients who underwent Cobas HPV and Papanicolaou (Pap) cytology cotesting from 2019 to 2020 were retrospectively reviewed. Surgical follow-up results were compared with Cobas HPV testing results in two populations., Results: A total of 2226 patients, including 921 women (mean age, 55.2 years) seen at the CPC and 1305 women (mean age, 49.3 years) seen at the GOC, were included. Specimens from GOC patients had a significantly higher HPV positivity rate than did those from CPC patients (22.9% vs. 10.1%; p < .001). Cobas HPV testing was positive in all seven CPC patients with surgical follow-up results showing CIN2+. Among 36 GOC patients with CIN2+ lesions, five patients had HPV-/Pap+ testing results. Although only seven CPC patients had CIN2+, Cobas HPV testing showed 100% sensitivity for predicting CIN2+ in this group. Sensitivity for CIN2+ was 86.5% in the GOC group, whereas 13.9% of GOC patients with CIN2+ had negative HPV testing results., Conclusions: Cobas HPV testing was highly efficacious for predicting CIN2+ lesions in the low-risk CPC population, which supports HPV primary screening for cervical cancer in low-risk populations. For high-risk patients, especially those with a history of CIN2+/cervical cancer, HPV/Pap cotesting may still be necessary to maintain a high clinical sensitivity for CIN2+., (© 2023 American Cancer Society.)

Aims: Cervical cancer remains a burden within Aotearoa New Zealand, with 2022 screening rates sitting 12.7% below target. The National Cervical Screening Programme has changed to primary human papillomavirus (HPV) testing for all screen-eligible people, with the aim for home self-testing. Little is known about the readiness of primary care for the change to self-testing and its associated challenges. A pilot HPV cervical cancer screening programme is being conducted in 17 practice centres. The aim of this study is to explore smear-taker knowledge at these centres about the use of primary HPV testing for cervical cancer screening., Methods: This is an ethically approved questionnaire study, with data from a structured web-based questionnaire sent to all smear-takers at the pilot centres., Results: We achieved a total completion rate of 57.8%. The average score for "Knowledge of HPV" was 56.5% (range=20-100%). The challenges to patient home HPV self-testing were felt to be overall "not at all" to "mildly challenging". Up to 73.3% of participants identified ongoing needs for further education., Conclusions: The findings indicate knowledge deficits regarding HPV testing for cervical cancer screening and a desire for the provision of further education. Overall, respondents felt that no major barriers to implementing HPV self-testing would occur., Competing Interests: Funding was provided by the Ministry of Health National Screening Unit, which included salaries for the authors on this submission (apart from SI). PS has done other funded work for the National Screening Unit. JN has had salary funding from the Health Research Council of New Zealand. CI received grants from the New Zealand Ministry of Health during the conduct of the study. JM is General Practice/Primary lead for the National Screening Unit. BL received grants from the New Zealand Health Research Council and the New Zealand Ministry of Health; she is a member of the New Zealand National Screening Unit HPV Programme Advisory and Action Group. AT has worked for Christchurch Heart Institute, Omics and Pacific Heart Health Laboratories, University of Otago, Christchurch, Canterbury Clinical Network Pasifika Caucus, and Pacific Peoples Advisory Committee, University of Canterbury. AT also has a voluntary role with P.A.C.I.F.I.C.A. Inc. SI, LM, BH, STW, MG and RB have nothing further to declare., (© PMA.)

Chlamydia trachomatis (CT) is the most common sexually transmitted infections globally, and CT infection can enhance HPV persistence. Epidemiological analysis has shown that patients with CT/HPV coinfection have a higher risk of developing cervical cancer and exhibit more rapid progression to cervical cancer than patients with HPV infection alone. However, the mechanism has not been fully elucidated. Here, we report that CT infection supports HPV persistence by further suppressing the functions of Langerhans cells (LCs); in particular, CT further activates the PI3K pathway and inhibits the MAPK pathways in LCs, and these pathways are frequently involved in the regulation of immune responses. CT/HPV coinfection also impairs LC functions by reducing the antigen-presenting ability and density of LCs. Moreover, CT/HPV coinfection can alter T-cell subsets, resulting in fewer CD4 + and CD8 + T cells and more infiltrating Tregs. Moreover, CT/HPV coinfection decreases the CD4 + /CD8 + T cell ratio to below 1, coinfection also induces greater T lymphocytes' apoptosis than HPV infection, thus impairing cell-mediated immunity and accelerating the progress to cervical cancer., (© 2024. The Author(s).)

Background: Implementation of high-risk human papillomavirus (hrHPV) screening has greatly reduced the incidence and mortality of cervical cancer. However, a triage strategy that is effective, noninvasive, and independent from the subjective interpretation of pathologists is urgently required to decrease unnecessary colposcopy referrals in hrHPV-positive women., Methods: A total of 3251 hrHPV-positive women aged 30-82 years (median = 41 years) from International Peace Maternity and Child Health Hospital were included in the training set (n = 2116) and the validation set (n = 1135) to establish Cervical cancer Methylation (CerMe) detection. The performance of CerMe as a triage for hrHPV-positive women was evaluated., Results: CerMe detection efficiently distinguished cervical intraepithelial neoplasia grade 2 or worse (CIN2 +) from cervical intraepithelial neoplasia grade 1 or normal (CIN1 -) women with excellent sensitivity of 82.4% (95% CI = 72.6 ~ 89.8%) and specificity of 91.1% (95% CI = 89.2 ~ 92.7%). Importantly, CerMe showed improved specificity (92.1% vs. 74.9%) in other 12 hrHPV type-positive women as well as superior sensitivity (80.8% vs. 61.5%) and specificity (88.9% vs. 75.3%) in HPV16/18 type-positive women compared with cytology testing. CerMe performed well in the triage of hrHPV-positive women with ASC-US (sensitivity = 74.4%, specificity = 87.5%) or LSIL cytology (sensitivity = 84.4%, specificity = 83.9%)., Conclusions: PCDHGB7 hypermethylation-based CerMe detection can be used as a triage strategy for hrHPV-positive women to reduce unnecessary over-referrals., Trial Registration: ChiCTR2100048972. Registered on 19 July 2021., (© 2024. The Author(s).)

Objectives: To ensure that the emerging methods for human papillomavirus (HPV) testing on self-collected samples in cervical screening are evaluated robustly., Study Design and Setting: We assess paired study designs for relative sensitivity of self-collected vs. traditional clinician-collected samples in detection of high-grade cervical intraepithelial neoplasia., Results: Designs considered are (D1) both samples at screening, with clinical actions triggered by HPV positivity; (D2) offering a self-sample test to clinician-collected HPV-positive women; (D3) as D2 but using a repeat clinician-sample as comparator; (D4) offering a choice of self- vs. clinician-sampling, and the alternative test in HPV-positive women; (D5) paired samples at referral appointment. D1 is simple to analyze but requires the largest sample size and referral of self-sample positive, clinician-sample negative women. D2 requires a much smaller sample size, and no change to clinical practice, and could be used to rule-in a test because estimates are conservative (against self-sampling). D3 mitigates this bias but requires a second clinician sample. D4 is only manageable where self-sampling already occurs. The liberal D5 might be used to rule-out a self-sampling test., Conclusion: A universal recommendation for an optimal study design is challenging. Staged validation might be useful with D5 as a gatekeeper for D1-D4., Competing Interests: Declaration of competing interest AB is member of the UK National Screening Committee Research and Methodology subgroup. KC reports research funding or consumables to support research in the last 3 years from Cepheid, Euroimmun, GeneFirst, SelfScreen, Hiantis Seegene, Roche, Abbott and Hologic, paid to employer. Professional Clinical Advisor to the English Cervical Screening Programme; member of various expert groups providing advice to the English Cervical Screening Programme including on HPV self-sampling; member of the working group that has provided advice to the Scottish Cervical Screening Programme on the potential use of HPV self-sampling within the program. AS is member of various expert groups providing advice to the English Cervical Screening Programme including on HPV self-sampling; holds an honorary contract with The University of Manchester to support research into HPV testing in urine samples and Professional Clinical Advisor to the English Cervical Screening Programme. JB reports grants with income to institution from the Dutch National Institute for Public Health and the Environment. (Rijksinstituut voor Volksgezondheid en Milieu, RIVM). MR reports previous research funding received to instution from the former Public Health England (now: NHS England and Department of Health/Office for Health Improvement and Disparities) for epidemiological evaluation of various cervical screening studies; member of various expert groups providing advice to the English Cervical Screening Programme; attended meetings with HPV test manufacturers; fees for attendance at advisory board and other meetings by Hologic, shared with employer., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Cervical cancer is an abnormal growth of cervical tissue epithelial cells due to persistent human papilloma virus (HPV) infection. Cynomolgus monkeys (Macaca fascicularis) can be naturally and spontaneously infected with M. fascicularis Papillomavirus Type 3 (MfPV3), a virus that is phylogenetically closely related to human oncogenic HPV (HPV-16 and HPV-34), and therefore a potentially beneficial for modeling HPV disease. This study aims to evaluate the expression of the integrin alpha 6 (ITGα6) receptor in cynomolgus monkeys spontaneously infected with MfPV3, which this receptor also found in human infected with HPV., Methods: The study was done on archived Formalin-fixed Paraffin-Embedded (FFPE) samples of uterine and cervix tissue of cynomolgus monkeys. Immunohistochemistry was also performed to quantify the expression levels of ITGα6., Results: The results showed 80% of the samples positive Cervical Intraepithelial Neoplasia (CIN) and increased expression of ITGα6 significantly in Positive-MfPV3 group than negative-MfPV3 group., Conclusions: This indicated the potential of cynomolgus monkeys as a spontaneous oncogenesis model of PV infection type., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To introduce HPV self-sampling and out-reach colposcopy clinic as interventions to improve the follow-up of HPV positive women in a community based cervical cancer screening programme., Methods: This was a prospective observational study conducted during October 2017 to August 2019 and 2977 women underwent cervical cancer screening using CareHPV test. Follow up colposcopy for HPV positive women were conducted at the rural health center and alternatively as out-reach clinics in their own villages and default rates were compared. HPV positive women were followed up at one-year. They were given an option of either having a follow-up HPV test performed by a health care worker (HCW) or by self-sampling. Compliance to follow up in these two modalities were compared. A validated questionnaire was given to women who had given an HPV self-sample to assess their awareness about HPV and cervical cancer., Results: During our initial round of cervical cancer screening using HPV as a primary screening modality, our HPV screen positive rate was 7.05% (210 out of 2977 women screened).  Our colposcopy rates following an initial invitation at the rural health centre was only 28.5%. Following this, we initiated out-reach colposcopy clinics at their own villages for HPV positive women and this increased colposcopy rates from 28.5% to 45.2%. The participation rate at one-year follow-up was increased from 40.5% to 60% by the introduction of self-sampling as a follow up option and 16.2% of women who were initially positive remained HPV positive at 12-14 months follow up. All women who were offered the option of self-sampling preferred it over a HCW collected sample., Conclusion: Our study showed that self-sampling could also be used effectively in the follow up of HPV positive women in the community. Outreach colposcopy clinics in their own villages enabled better follow up of HPV positive women.

Objectives: Organisation of a screening programme influences programme resilience to a disruption as COVID-19. Due to COVID-19, the Dutch human papillomavirus-based cervical screening programme was temporarily suspended. Afterwards, multiple measures have been taken to catch-up participation. This study aimed to investigate programme resilience by examining the effect of COVID-19 and programme measures taken on participation in cervical screening., Study Design: Observational cohort study., Methods: Data from the national screening registry and Dutch nationwide pathology databank (Palga) were used on invitations and follow-up in 2018/2019 (pre-COVID) and 2020 (COVID). Sending invitations, reminders and self-sampling kits were suspended from March to July 2020. Main outcome measures include distribution of participant characteristics (age, region and screening history), participation rates by age and region, time between invitation and participation (i.e. response time) and self-sampling use per month., Results: Participation rate was significantly lower in 2020 (49.8%) compared to 2018/19 (56.8%, P < 0.001), in all ages and regions. Compared to 2018/19, participation rates decreased most in women invited from January to March 2020 (-6.7%, -9.1% and -10.4%, respectively). From August, participation rates started to recover (difference between -0.8% and -2.7%). Median response time was longer in February and March (2020: 143 and 173 days; 2018/19: 53 and 55 days) and comparable from July onwards (median difference 0-6 days). Self-sampling use was higher in 2020 (16.3%) compared to 2018/19 (7.6%)., Conclusions: The pandemic impacted participation rates in the Dutch cervical screening programme, especially of women invited before the programme pause. Implementation of self-sampling in national cervical screening programmes could increase participation rates and could serve as an alternative screening method in times of exceptional health care circumstances, such as a pandemic. Due to the well-organised programme and measures taken to catch-up participation, the impact of COVID-19 on the screening programme remained small., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Approximately 500,000 women are diagnosed with cervical cancer annually, with high-grade cervical intraepithelial neoplasia (CIN) estimated to be 20 times higher. The diathermy ablation is an inexpensive minimally invasive surgeries for CIN. However, little is known about the treatment outcomes. A prospective clinical trial was therefore conducted to evaluate ablation outcomes based on detailed colposcopy findings, cytology, and biopsy results over a two-year period. We enrolled CIN2 (n = 32) and CIN3 (n = 7) patients. Eligibility criteria included: aged between 29 and 49 (median: 36, mean: 36.3), visible transformation zone with high-grade lesions not entirely occupying the cervix, and histologically diagnosed with CIN2 or CIN3. Cytology and HPV genotyping were performed, and colposcopic findings were evaluated. Colposcopy-guided diathermy ablation was conducted by a certified gynecologic oncologist. The incidence of recurrent or residual disease was 5.1% (2/39, 95% confidence interval: - 0.02 to 0.12). The prevalence of HPV infection at 12 months decreased after surgery, as 67.6% (23/34, 0.52-0.83) of patients were HPV-negative. No severe adverse events were reported, while there were five pregnancies with full-term deliveries. The promising outcome was possibly due to selection of rigorous surgical indication and skilled surgical techniques. The study highlights the importance of experienced and skilled colposcopists.TrialRegistry This study was registered in the clinical trial registration system of the University hospital Medical Information Network Clinical Trials Registry (UMIN-CTR ID: UMIN000024483). Open for the trial to the public through the website: 01/11/2016. First registration of the patient: 30/01/2017., (© 2024. The Author(s).)

Background: Screening participation at recommended intervals is a crucial component of cervical cancer prevention effectiveness. However, little is known regarding the rate of re-screening in a Sub-Saharan context. This study aimed to estimate the re-screening rate of women in a semi-rural after an initial HPV-based screening and identify factors that influence adherence., Methods: This cohort study at the Annex Regional Hospital of Dschang enrolled women screened for cervical cancer over 5 years ago and due for re-screening. Women who initially tested HPV-positive (n = 132) and a random sample of HPV-negative women (n = 220) participated in a telephone survey between October 2021 and March 2022 to assess re-screening participation and reasons. Sociodemographic factors were collected, and associations with rescreening were evaluated., Results: A total of 352 participants aged under 50 years (mean age 37.4 years) were contacted, and 203 (58.0%) completed the survey. The proportion of women who complied with the screening recommendation was 34.0% (95% CI 27.5% - 40.5%), The weighted re-screening proportion was 28.4%. Age, marital status, education level, type of employment, and place of residence were not associated with the rate of re-screening. Main reported barriers to re-screening were lack of information (39.0%), forgetfulness (39.0%), and impression of being in good health (30.0%). Women who remembered the recommended screening interval were 2 to 3 times more likely to undergo re-screening (aOR (adjusted odds ratio) = 2.3 [1.2-4.4], p = 0.013). Human papilloma virus- positive status at the initial screening was also associated with the re-screening((aOR) (95% CI): 3.4 (1.8-6.5)., Conclusion: Following an initial Human Papilloma Virus-based screening campaign in the West Region of Cameroon, one third of women adhered to re-screening within the recommended timeframe. Existing screening strategies would benefit from developing better information approaches to reinforce the importance of repeated cervical cancer screening., (© 2024. The Author(s).)

The vaginal microbiota plays a crucial role in female reproductive health and is considered a biomarker for predicting disease outcomes and personalized testing. However, its relationship with human papillomavirus (HPV) infection and cervical cancer is not yet clear. Therefore, this article provides a review of the association between the vaginal microbiota, HPV infection, and cervical cancer. We discuss the composition of the vaginal microbiota, its dysbiosis, and its relationship with HPV infection, as well as potential mechanisms in the development of cervical cancer. In addition, we assess the feasibility of treatment strategies such as probiotics and vaginal microbiota transplantation to modulate the vaginal microbiota for the prevention and treatment of diseases related to HPV infection and cervical cancer. In the future, extensive replication studies are still needed to gain a deeper understanding of the complex relationship between the vaginal microbiota, HPV infection, and cervical cancer, and to clarify the role of the vaginal microbiota as a potential biomarker for predicting disease outcomes, thus providing a theoretical basis for personalized testing., 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 Zhang, Ma, Zhang, Ma, Wang, Yang, Jia, Wu and Wang.)

Purpose: Cervical cancer is a common gynecological malignancy, pathologically associated with persistent infection of high-risk types of human papillomavirus (HPV). Previous studies revealed that HPV-positive cervical cancer displays genomic instability; however, the underlying mechanism is not fully understood., Methods: To investigate if DNA damage responses are aggravated in precancerous lesions of HPV-positive cervical epithelium, cervical tissues were biopsied and cryosectioned, and subjected to immunofluorescent staining. Cloned HA-tagged E6 and E7 genes of HPV16 subtype were transfected into HEK293T or C33A cells, and indirect immunofluorescent staining was applied to reveal the competency of double strand break (DSB) repair. To test the synthetic lethality of E7-indued HRD and PARP inhibitor (PARPi), we expressed E7 in C33A cells in the presence or absence of olaparib, and evaluated cell viability by colony formation., Results: In precancerous lesions, endogenous DNA lesions were elevated along with the severity of CIN grade. Expressing high-risk viral factor (E7) in HPV-negative cervical cells did not impair checkpoint activation upon genotoxic insults, but affected the potential of DSB repair, leading to homologous recombination deficiency (HRD). Based on this HPV-induced genomic instability, the viability of E7-expressing cells was reduced upon exposure to PARPi in comparison with control cells., Conclusion: In aggregate, our findings demonstrate that HPV-E7 is a potential driver for genome instability and provides a new angle to understand its role in cancer development. The viral HRD could be employed to target HPV-positive cervical cancer via synthetic lethality., (© 2024. The Author(s).)

Background: Cervical cancer is a global disease and it is well established that cervical cancer is caused by human papillomavirus (HPV). In Sweden self-sampling for HPV is now used as a complement to sampling performed by a midwife. However, there is a lack of knowledge on how older women perceive the self-sampling compared to the sampling performed by a midwife. Therefore, the aim of the study was to describe how women, aged 64 years and older, perceived the process of self-sampling and sampling performed by a midwife for HPV-testing., Methods: Eighteen women were included in a qualitative interview study, and a phenomenographic approach was used for the analysis of the interviews., Results: Three descriptive categories emerged: Confidence in sampling, Facilitating participation and Being informed. Within the categories, eight conceptions emerged describing the variation relating to how the women perceived the process of self-sampling and sampling performed by a midwife., Conclusions: Women in this study describe confidence in self-sampling for HPV-testing and that the self-sampling was saving time and money, both for themselves and for society. Information in relation to an HPV-positive test result is of importance and it must be kept in mind that women affected by HPV may feel guilt and shame, which health care professionals should pay attention to. This knowledge can be used in education of health care staff., Trial Registration: https://researchweb.org/is/fourol/project/228071 . Reg. no 228,071., (© 2024. The Author(s).)