Improving the effectiveness of cervical cancer screening: Managing positive high-risk human papillomavirus results.

Introduction: Good compliance of the management of abnormal results is important for effective cervical screening. This study investigated the rate of surveillance and follow-up outcomes for human papillomavirus (HPV)-positive women in cervical screening. Method: Women on surveillance by repeat HPV testing were identified in a prospectively managed database. Data retrieved included women's age, country residence status, history of colposcopy, HPV-DNA status on the first and repeat tests, dates of follow-up during the 5 years since the initial screening, and histological diagnosis of cervical lesions. The main outcome measures were compliance rate for repeat HPV testing, regression and persistence rates of HPV subtypes, and detection rate of high-grade lesions (CIN2+). Results: This analysis included 680 residents in the community, mean age 44.8 (95% confidence interval 20.1-69.5) years. The compliance rate of repeat testing was 28.2% at 12 months and, cumulatively, 42.8% for the entire 5-year follow-up period. The rates were unaffected by age (P=0.5829) nor prior colposcopy (P=0.1607). There were 5 (1.7%) cases of CIN2+ detected. Of 391 women on longitudi-nal follow-up, 194 (60.8%) cleared their HPV infection. Some women with multiple HPV infection cleared 1 but not the other subtype(s). Thus, the regression rate was 90.3% for HPV-16, 87.0% for HPV-18 and 65.2% for HPV-12-others (P=0.001). The annualised HPV regression rates were similar for HPV subtypes and for each follow-up year. Conclusion: Surveillance of HPV positivity is clinically important for detecting high-grade lesions. Despite a high regression rate of HPV, surveillance hesitancy is a serious weakness in routine cervical screening.

Is there a need for screening of cervical HPV infections and carcinoma?

Antenatal cervical screening aims to detect cervical intraepithelial neoplasms as precancerous lesions and invasive cervical cancer. Whether this screening is performed routinely during pregnancy varies depending on each country's screening participation rates, guidelines, and the risks to the pregnant woman. In some countries with the high rate of routinely implemented cervical screening among the target women, women are recommended to defer cervical screening intentionally to post-delivery, though having screening in consultation with physicians may be possible if routine screening overlaps. However, when cervical screening rate in fertile women is low and the incidence of cervical cancer is high, cervical screening during pregnancy may play an important role in the early detection of cervical cancer. Cervical screening using high-risk human papillomavirus (HPV) testing is accepted worldwide as a highly sensitive and objective test method, and it should replace traditional primary cervical cytology in the future. However, the benefits and disadvantages of using HPV testing in pregnant women is unclear because a false positive rate may be increased due to pregnant women being generally under an immunosuppressed condition.

Experiences of Self-Sampling and Future Screening Preferences in Non-Attenders Who Returned an HPV Vaginal Self-Sample in the YouScreen Study: Findings From a Cross-Sectional Questionnaire.

BACKGROUND: We assessed experiences of human papillomavirus (HPV) vaginal self-sampling and future screening preferences in an ethnically and socio-economically diverse group of women overdue for cervical screening. SETTING AND PARTICIPANTS: A postal questionnaire was embedded in the YouScreen self-sampling trial in England: 32.5% (2712/8338) of kit completers returned the survey. Kit non-completers were encouraged to return a questionnaire, but no responses were received. Participants were ethnically diverse (40.3% came from ethnic minority backgrounds), and 59.1% came from the two most deprived quintiles. Differences in confidence in kit completion, trust in the test results and intention to attend a follow-up test if HPV-positive were evaluated using Pearson's χ2 analyses. Binary logistic regression models explored predictors of a future screening choice and preferences for urine versus vaginal self-sampling. RESULTS: Most kit-completers reported high confidence in self-sampling (82.6%) and high trust in the results (79.9%), but experiences varied by ethnicity and screening status. Most free-text comments were positive but some reported difficulties using the device, pain or discomfort. Most women would opt for self-sampling in the future (71.3% vs. 10.4% for a clinician-taken test) and it was more often preferred by ethnic minority groups, overdue screeners and never attenders. Urine self-tests were preferred to vaginal tests (41.9% vs. 15.4%), especially among women from Asian, Black or Other Ethnic backgrounds. CONCLUSIONS: Kit-completers were confident, found the test easy to complete, and trusted the self-sample results. However, experiences varied by ethnic group and some women highlighted difficulties with the kit. Most women would prefer self-sampling in the future, but it was not a universal preference, so offering a choice will be important. PATIENT OR PUBLIC CONTRIBUTION: We did not have direct patient and public involvement and engagement (PPIE) in the questionnaire design. However, patients and public representatives did input into the design of the YouScreen trial and reviewed the wider study materials (e.g. participant information sheet). TRIAL REGISTRATION: This questionnaire study was embedded in the YouScreen trial. The protocol for the YouScreen trial is available at https://www.isrctn.com/ISRCTN12759467. The National Institute for Health Research 43 Clinical Research Network (NIHR CRN) Central Portfolio Management System (CPMS) ID is 4441934.

How do young women approaching screening age interpret the NHS cervical screening leaflet? A mixed methods study of identifying interpretation difficulties, barriers, facilitators, and leaflet interpretation, engagement and future screening behaviour.

BACKGROUND: Cervical cancer is a common cancer among young women aged 25-29 in England, and the NHS cervical screening leaflet is the first point of contact for those being invited for their first screening. This study aimed to explore how young women (18-24) understand and engage with the leaflet, as well as the barriers and facilitators associated with its interpretation, engagement, and screening intentions. METHODS: The study used a mixed-methods approach, including a survey (n = 120) to identify interpretation difficulties and how they were affected by different characteristics, and a follow-up interview (n = 10) to assess the utility of the leaflet, identify issues with its practicality, and determine the factors that influence screening intentions. RESULTS: The survey results showed that interpretation difficulties were common, particularly regarding HPV assessment, screening results, additional tests/treatment, and screening risks. Lower interpretation accuracy was associated with lower numeracy scores and non-white ethnicity. Despite these difficulties, participants had high confidence and motivation to engage with the leaflet. The interviews revealed knowledge gaps, issues with the leaflet's practicality, and a preference for digital information. Factors that were identified as barriers and facilitators of leaflet interpretation, engagement, and screening intentions included knowledge, social influence, beliefs about consequences, environmental context and resources, social role and identity, emotions and intentions. CONCLUSION: The current leaflet does not provide enough information for young women to make an informed decision about screening attendance. Implementing a digital invitation featuring simplified gist representation, targeted behaviour change techniques (BCTs), videos, and interactive tools can enhance education and promote screening behaviour. Future research should consider using digital tools and strategies to address existing barriers related to interpretation and engagement.

Working together with people with intellectual disability to make a difference: a protocol for a mixed-method co-production study to address inequities in cervical screening participation.

Introduction: Cervical cancer is one of the most preventable cancers yet remains a disease of inequity for people with intellectual disability, in part due to low screening rates. The ScreenEQUAL project will use an integrated knowledge translation (iKT) model to co-produce and evaluate accessible cervical screening resources with and for this group. Methods: Stage 1 will qualitatively explore facilitators and barriers to screening participation for people with intellectual disability, families and support people, healthcare providers and disability sector stakeholders (n ≈ 20 in each group). An accessible multimodal screening resource, accompanying supporting materials for families and support people, and trauma-informed healthcare provider training materials will then be co-produced through a series of workshops. Stage 2 will recruit people with intellectual disability aged 25 to 74 who are due or overdue for screening into a single-arm trial (n = 48). Trained support people will provide them with the co-produced resource in accessible workshops (intervention) and support them in completing pre-post questions to assess informed decision-making. A subset will participate in qualitative post-intervention interviews including optional body-mapping (n ≈ 20). Screening uptake in the 9-months following the intervention will be measured through data linkage. Family members and support people (n = 48) and healthcare providers (n = 433) will be recruited into single-arm sub-studies. Over a 4-month period they will, respectively, receive the accompanying supporting materials, and the trauma-informed training materials. Both groups will complete pre-post online surveys. A subset of each group (n ≈ 20) will be invited to participate in post-intervention semi-structured interviews. Outcomes and analysis: Our primary outcome is a change in informed decision-making by people with intellectual disability across the domains of knowledge, attitudes, and screening intention. Secondary outcomes include: (i) uptake of screening in the 9-months following the intervention workshops, (ii) changes in health literacy, attitudes and self-efficacy of family members and support people, and (iii) changes in knowledge, attitudes, self-efficacy and preparedness of screening providers. Each participant group will evaluate acceptability, feasibility and usability of the resources. Discussion: If found to be effective and acceptable, the co-produced cervical screening resources and training materials will be made freely available through the ScreenEQUAL website to support national, and potentially international, scale-up.

Inclusive language in health policy - a timely case (study) of cervical screening in Australia.

Language is important in health policy development. Policy changes in Australia to increase cervical screening offers a timely case example to explore the function of inclusive language in health policy. Gender and sexuality diverse people with a cervix have been largely invisible within health promotion programs, which has led to reduced awareness of, and access to, cervical screening. Twenty-eight semi-structured interviews were conducted with 29 key informants between April and October 2022 about the role of inclusive language in cervical screening policy, promotion, and delivery in the context of a national program to promote cervical screening. Three themes were identified from what key informants believed to be the role of inclusive language: (1) the common goal of inclusive language as policy advocacy for broader inclusivity; (2) the inevitable partiality of inclusive language in policy as an opportunity to start conversation; and (3) policy as a bridge between essential but diffuse components of the health sector with multidirectional influences. Inclusive language was seen to operationalise equity in health policy within the broader aim of eliminating cervical cancer among under-screened populations.

Primary and secondary prevention of cervical cancer among Italian AFAB transgender people.

OBJECTIVE: Currently, available data on preventive measures for Human Papillomavirus (HPV) infection and cervical cancer in the transgender assigned female at birth (AFAB) community are extremely limited. Our aim was to analyze adherence to primary and secondary cervical cancer prevention screening programs among transgender AFAB people attending our gender clinic. METHODS: Transgender AFAB people attending our center were recruited. Anamnestic data were collected for each person through completion of a medical history form and medical records. Variables recorded included previous HPV vaccination, adherence to regional screening programs (Pap smear or HPV DNA test), subject age, duration of current or prior gender-affirming hormone therapy (GAHT) and whether gender affirmation surgery (GAS) with hysterectomy had been performed. Open questions regarding reasons for not undergoing screening tests were also included. RESULTS: In this cross-sectional study, 263 AFAB transgender people were included, with a mean age of 30.6 ± 10.5 years. GAS with hysterectomy had been performed on 37.6 % of these people. Of our participants, 71.7 % who were born after 1998 (the first cohort to receive HPV vaccination invitations in Italy) had been vaccinated for HPV. Seventy-four-point-nine percent of participants who were still eligible for cervical screening had never undergone Pap smear or HPV DNA testing, whereas those who had undergone at least one cervical screening had done so on average 4.2 ± 4.5 years ago. CONCLUSION: HPV vaccination prevalence in the AFAB transgender population born after 1998 is in line with the Italian AFAB general population. However, adherence to cervical cancer screening programs in the transgender AFAB population appears to be lower in comparison to the cisgender population. Further efforts are required from the medical community to enhance AFAB transgender people's adherence to HPV vaccination and to cervical screening.

Actions speak louder than words; pediatricians, gynecologists, nurses, and other mothers' perspectives on the human papillomavirus vaccine: an Istanbul multicenter study.

Introduction: Gynecologists and pediatricians have an essential duty to prevent cervical cancer. In this study, we compared the compliance of gynecologists (n = 22) and pediatricians (n = 49) with nurse/midwife (n = 66) and non-medical moms (n = 120) with regards to cervical cancer precautions. Methods: A questionnaire was used to gather data on their demographics, personal vaccination and screening practices, children's immunization status, and awareness of cervical cancer prevention. Results: The findings demonstrated that gynecologists and pediatricians were better than others at understanding the risk factors and prevention of cervical cancer. It was noted that compared to other groups, physician mothers and their offspring had higher vaccination rates (n = 13, 18.3%; n = 10, 29.4%, respectively). Medical professionals typically provided thorough and accurate answers to informational questions. More frequent Pap smear tests were performed by gynecologists. It was noted that mothers who worked as pediatricians and nurses/midwives neglected their own screening needs. Discussion: This questionnaire survey sought to ascertain Istanbul's health professionals' present opinions regarding HPV vaccination. Healthcare professionals should be the first to receive information on HPV vaccination and cervical cancer incidence reduction. The public could then readily use them as an example.

Trust in cervical screening and attributions of blame for interval cancers following a national controversy.

OBJECTIVES: This study investigated levels of trust and attributions of blame in connection with a cervical screening programme following a controversy related to the programme's audit, incorporating an experimental test of the effectiveness of new information materials. DESIGN: We compared responses in Ireland (N = 872) to equivalent responses in Scotland (N = 400). Participants in Ireland were randomly assigned to either a treatment group that received the information materials or a control group that did not. Participants then responded to questions about their trust in cervical screening and to whom they would attribute blame in a range of scenarios describing women diagnosed with cervical cancer between screening rounds. RESULTS: Results showed that the control group in Ireland had lower trust and attributed higher blame towards screening services than participants in Scotland. However, exposure to information materials in the treatment group improved trust and reduced blame. CONCLUSIONS: The findings suggest that public controversies influence perceptions of screening programmes and underscore the importance of transparent, choice-based communication in mitigating these effects. The findings have valuable implications for screening services worldwide as all screening programmes will have associated false negative and false positive results.

Practitioners support and intention to adopt universal access to self-collection in Australia's National Cervical Screening Program.

OBJECTIVE: Primary care practitioners are crucial to engaging people in Australia's national cervical screening program. From July 2022, practitioners have been able to offer all screen-eligible people the choice to collect their own self-collected sample; an option introduced to increase equity. This study explored how practitioners are intending to incorporate universal access to self-collection into their clinical care. METHODS: Semi-structed interviews with 27 general practitioners, nurses, and practice managers from 10 practices in Victoria, Australia conducted between May and August 2022. Interviews were deductively coded, informed by the Consolidated Framework for Implementation Research. The Diffusion of Innovations theory was used to categorise intention to provide self-collection. RESULTS: Participants were supportive of universal access to self-collection, citing benefits for screen-eligible people and that it overcame the limited adaptability of the previous policy. Most participants' practices (n = 7, 70%) had implemented or had plans to offer the option for self-collection to all. Participants deliberating whether to provide universal access to self-collection held concerns about the correct performance of the self-test and the perceived loss of opportunity to perform a pelvic examination. Limited time to change practice-level processes and competing demands within consultations were anticipated as implementation barriers. CONCLUSIONS: The extent to which self-collection can promote equity within the program will be limited without wide-spread adoption by practitioners. Communication and education that addresses concerns of practitioners, along with targeted implementation support, will be critical to ensuring that self-collection can increase participation and Australia's progression towards elimination of cervical cancer.

Knowledge about cervical cancer in young Portuguese women: a cross-sectional study.

Introduction: Health literacy is crucial to adherence to medical interventions in therapeutics, prevention, and diagnosis. The basis for literacy is knowledge. To accomplish the goals for the elimination of cervical cancer, one of the most prevalent and preventable cancers, we must understand the determinants of non-adherence and address them specifically to ensure patients' active participation. Aim: To determine women's knowledge regarding the manifestations of cervical cancer and its prevention. Materials and methods: We conducted a cross-sectional study in an urban population from northern Portugal. Women aged 18 to 30 years were randomly assigned to answer the Cervical Cancer Awareness Measure questionnaire, including questions of knowledge about the causes and symptoms of cervical cancer, prospecting for individual and social-related determinants. Results: The total number of participants was 270, with a mean age of 24.7 years. Knowledge about symptoms scored 5.4 ± 2.6, with a maximum of 12 points, and knowledge about the causes scored 5.7 ± 1.9, with a maximum of 11 points. The correlation between both was 0.334. High education, high socio-economic status, self-perception of one's capacity to recognize symptoms, and knowledge about the HPV vaccine were associated with better knowledge. Discussion: Portuguese women present low knowledge about cervical cancer, potentially affecting their health through exposure to risk situations and non-adherence to routine screening.

Less known but greatly feared: Cervical cancer in Ethiopia community awareness.

To improve a community's awareness and attitude towards cervical cancer, strong evidence is needed to inform contextually appropriate policies. This study aims to explore community awareness about cervical cancer from the perspective of women, men and health extension workers (HEWs). The research was conducted from May to July 2021 in Jimma, Ethiopia. A total of 23 in-depth interviews were conducted. The study included married and unmarried women (15-19 and 25-29 years old), men of similar ages (married and unmarried), and HEWs. Furthermore, eight separate focus group discussions (FGDs) were conducted with both men and women. Thematic analysis was used to draw findings from the interviews and FGDs. Community awareness about cervical cancer was very limited. However, people who knew of it believed that cancer is fatal. A few participants were aware of cervical cancer through its symptoms, but most people did not know it by name and had never heard about HPV as the cause of cervical cancer. There was little understanding of HPV risk, transmission factors, prevention, vaccination, screening, or treatment. Participants considered their participation in this study as their first chance to learn about the disease. HEWs had limited knowledge about HPV and cervical cancer. Study participants demonstrated favorable attitudes towards HPV vaccination, cervical screening, and treatment after they received basic information about cervical cancer from the data collectors. Participants and HEWs strongly suggested awareness creation programs for the wider community members, including active involvement of men and HEWs in cervical cancer interventions. There is a critical information gap regarding cervical cancer, its cause and risk factors, HPV transmission, cervical screening, and treatment programs. Limited community awareness leads to poor uptake of cervical screening in the few settings where it is available. Therefore, community awareness programs about HPV, cervical cancer, and available services should improve the community's awareness of cervical cancer and HPV.

Urine high-risk human papillomavirus testing as an alternative to routine cervical screening: A comparative diagnostic accuracy study of two urine collection devices using a randomised study design trial.

OBJECTIVE: To evaluate the sensitivity of human papillomavirus (HPV) tested urine to detect high-grade cervical precancer (cervical intraepithelial neoplasia grade 2+ [CIN2+]) using two urine collection devices. DESIGN: Randomised controlled trial. SETTING: St Mary's Hospital, Manchester, UK. POPULATION: Colposcopy attendees with abnormal cervical screening; a total of 480 participants were randomised. Matched urine and cervical samples were available for 235 and 230 participants using a first-void urine (FVU)-collection device and standard pot, respectively. METHODS: Urine was self-collected and mixed with preservative - randomised 1:1 to FVU-collection device (Novosanis Colli-pee® 10 mL with urine conservation medium [UCM]) or standard pot. Matched clinician-collected cervical samples were taken before colposcopy. HPV testing used Roche cobas® 8800. A questionnaire evaluated urine self-sampling acceptability. MAIN OUTCOME MEASURES: The primary outcome measured sensitivity of HPV-tested urine (FVU-collection device and standard pot) for CIN2+ detection. Secondary outcomes compared HPV-tested cervical and urine samples for CIN2+ and evaluated the acceptability of urine self-sampling. RESULTS: Urine HPV test sensitivity for CIN2+ was higher with the FVU-collection device (90.3%, 95% CI 83.7%-94.9%, 112/124) than the standard pot (73.4%, 95% CI 64.7%-80.9%, 91/124, p = 0.0005). The relative sensitivity of FVU-device-collected urine was 0.92 (95% CI 0.87-0.97, pMcN = 0.004) compared with cervical, considering that all women were referred after a positive cervical HPV test. Urine-based sampling was acceptable to colposcopy attendees. CONCLUSIONS: Testing of FVU-device-collected urine for HPV was superior to standard-pot-collected urine in colposcopy attendees and has promising sensitivity for CIN2+ detection. General population HPV testing of FVU-device-collected urine will establish its clinical performance and acceptability as an alternative to routine cervical screening.

Clinical Validation of the Vitro HPV Screening Assay for Its Use in Primary Cervical Cancer Screening.

Many scientific societies have issued guidelines to introduce population-based cervical cancer screening with HPV testing. The Vitro HPV Screening assay is a fully automatic multiplex real-time PCR test targeting the L1 GP5+/GP6+ region of HPV genome. The assay detects 14 high risk (HR) HPV genotypes, identifying individual HPV16 and HPV18 genotypes, and the HPV-positive samples for the other 12 HR HPV types are subsequently genotyped with the HPV Direct Flow Chip test. Following international guidelines, the aim of this study was to validate the clinical accuracy of the Vitro HPV Screening test on ThinPrep-collected samples for its use as primary cervical cancer screening, using as comparator the validated cobas® 4800 HPV test. The non-inferiority analysis showed that the clinical sensitivity and specificity of the Vitro HPV Screening assay for a diagnosis of cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) were not inferior to those of cobas® 4800 HPV (p = 0.0049 and p < 0.001 respectively). The assay has demonstrated a high intra- and inter-laboratory reproducibility, also among the individual genotypes. The Vitro HPV Screening assay is valid for cervical cancer screening and it provides genotyping information on HPV-positive samples without further sample processing in a fully automated workflow.

Projected Time for the Elimination of Cervical Cancer Under Various Intervention Scenarios: Age-Period-Cohort Macrosimulation Study.

BACKGROUND: The World Health Organization aims for the global elimination of cervical cancer, necessitating modeling studies to forecast long-term outcomes. OBJECTIVE: This paper introduces a macrosimulation framework using age-period-cohort modeling and population attributable fractions to predict the timeline for eliminating cervical cancer in Taiwan. METHODS: Data for cervical cancer cases from 1997 to 2016 were obtained from the Taiwan Cancer Registry. Future incidence rates under the current approach and various intervention strategies, such as scaled-up screening (cytology based or human papillomavirus [HPV] based) and HPV vaccination, were projected. RESULTS: Our projections indicate that Taiwan could eliminate cervical cancer by 2050 with either 70% compliance in cytology-based or HPV-based screening or 90% HPV vaccination coverage. The years projected for elimination are 2047 and 2035 for cytology-based and HPV-based screening, respectively; 2050 for vaccination alone; and 2038 and 2033 for combined screening and vaccination approaches. CONCLUSIONS: The age-period-cohort macrosimulation framework offers a valuable policy analysis tool for cervical cancer control. Our findings can inform strategies in other high-incidence countries, serving as a benchmark for global efforts to eliminate the disease.

HPV-associated cervicovaginal microbiome and host metabolome characteristics.

BACKGROUND: Cervicovaginal microbiome plays an important role in the persistence of HPV infection and subsequent disease development. However, cervicovaginal microbiota varied cross populations with different habits and regions. Identification of population-specific biomarkers from cervicovaginal microbiota and host metabolome axis may support early detection or surveillance of HPV-induced cervical disease at all sites. Therefore, in the present study, to identify HPV-specific biomarkers, cervicovaginal secretion and serum samples from HPV-infected patients (HPV group, n = 25) and normal controls (normal group, n = 17) in Xichang, China were collected for microbiome (16S rRNA gene sequencing) and metabolome (UHPLC-MS/MS) analysis, respectively. RESULTS: The results showed that key altered metabolites of 9,10-DiHOME, α-linolenic acid, ethylparaben, glycocholic acid, pipecolic acid, and 9,12,13-trihydroxy-10(E),15(Z)-octadecadienoic acid, correlating with Sneathia (Sneathia_amnii), Lactobacillus (Lactobacillus_iners), Atopobium, Mycoplasma, and Gardnerella, may be potential biomarkers of HPV infection. CONCLUSION: The results of current study would help to reveal the association of changes in cervicovaginal microbiota and serum metabolome with HPV infections.

Long-term prediction by DNA methylation of high-grade cervical intraepithelial neoplasia: Results of the ARTISTIC cohort.

Methylation markers have shown potential for triaging high-risk HPV-positive (hrHPV+) women to identify those at increased risk of invasive cervical cancer (ICC). Our aim was to assess the performance of the S5 DNA methylation classifier for predicting incident high-grade cervical intraepithelial neoplasia (CIN) and ICC among hrHPV+ women in the ARTISTIC screening trial cohort. The S5 classifier, comprising target regions of tumour suppressor gene EPB41L3 and L1 and L2 regions of HPV16, HPV18, HPV31, and HPV33, was assayed by pyrosequencing in archived hrHPV+ liquid-based samples from 343 women with high-grade disease (139 CIN2, 186 CIN3, and 18 ICC) compared to 800 hrHPV+ controls. S5 DNA methylation correlated directly with increasing severity of disease and inversely with lead time to diagnosis. S5 could discriminate between hrHPV+ women who developed CIN3 or ICC and hrHPV+ controls (p <.0001) using samples taken on average 5 years before diagnosis. This relationship was independent of cytology at baseline. The S5 test showed much higher sensitivity than HPV16/18 genotyping for identifying prevalent CIN3 (93% vs. 61%, p = .01) but lower specificity (50% vs. 66%, p <.0001). The S5 classifier identified most women at high risk of developing precancer and missed very few prevalent advanced lesions thus appearing to be an objective test for triage of hrHPV+ women. The combination of methylation of host and HPV genes enables S5 to combine the predictive power of methylation with HPV genotyping to identify hrHPV-positive women who are at highest risk of developing CIN3 and ICC in the future.

Cervical cancer in a transgender man: lessons learnt to improve care.

We describe a case of rapid progression of cervical dysplasia to stage IVB cervical cancer in a previously healthy transgender young adult man on testosterone therapy. The cancer diagnosis came 7 months after routine pap smear showed low-grade dysplasia with high-risk human papillomavirus in preparation for gender-affirming hysterectomy/bilateral-salpingo-oophorectomy. After diagnosis, our patient faced unique challenges as a transgender man receiving gynecologic oncology care. This case highlights the challenges of and barriers to cervical cancer screening and treatment that transgender men confront. This case also considers whether gender-affirming testosterone therapy is associated with cervical cancer risk. We offer suggestions on how to improve cervical cancer screening and treatment for the transgender population.

The impact of alternate HPV vaccination and cervical screening strategies in Japan: a cost-effectiveness analysis.

Background: The Japanese 2020 cervical screening guidelines recommend conventional cervical cytology screening every 2-years for women aged 20-69 years. The nonavalent human papillomavirus (HPV) vaccine has also recently been approved in Japan. We therefore evaluated the cost-effectiveness of cervical cancer screening strategies alongside universal nonavalent HPV vaccination of girls (12-16 years). Methods: A cost-effectiveness analysis was performed using an age-specific Markov microsimulation model for Japan to evaluate total costs, quality adjusted life-years (QALYs) gained, incremental cost-effectiveness ratios (ICER), colposcopies, biopsies, precancer and cervical cancer treatments for 29 combined vaccination and screening strategies (conventional cytology, liquid-based cytology (LBC), HPV testing, and HPV self-collection). A cohort of 100,000 girls (12-16 years old) over a lifetime offered the nonavalent HPV vaccine was used (current vaccination coverage = 0.08%, current screening coverage = 43.7%). A discount rate of 3% was applied to costs and QALYs. Univariate and probabilistic sensitivity analysis was performed to assess robustness of the findings. Costs were reported in US dollars (2023). Findings: Compared with conventional cytology, evaluated strategies would incur an additional cost of US$839,280-738,182,669 and gain 62,755-247,347 quality-adjusted-life-years. HPV testing distinguishing HPV16/18 with reflex LBC (3-yearly) would be most cost-effective (ICER = US$7511 per QALY gained). At a willingness-to-pay (WTP) of 1-times gross domestic product (GDP) per capita, the probability of it being cost-effective was 70%. At historically high vaccination coverage (70%) ICERs decreased overall but did not affect the ranking of the most cost-effective strategy. While a 5-yearly interval became more cost-effective than a 3-yearly interval. Including HPV self-collection for under-screened women made all strategies more cost-effective. Interpretation: At current cervical screening participation (43.7%) and low vaccination coverage (<1.0%), HPV testing distinguishing HPV16/18 with reflex LBC (3-yearly) would be the most cost-effective screening strategy compared to conventional cytology (2-yearly). Funding: Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (17H03589) and Grants of the National Cancer Center Japan (Gan Kenkyu Kaihatsuhi 31-A-20 and 2023-A-23).

Analysis of the Differences between Bethesda Groups according to Conventional Smear and Liquid-Based Cytology Methods in Cervicovaginal Cytology: A Single-Center Experience with 165,915 Cases.

INTRODUCTION: Liquid-based cytology (LBC) has replaced conventional smear (CS) in the world. In this study, through a series with a large number of cases, we aimed to make a comparison and general evaluation in all groups, primarily epithelial abnormalities, according to LBC and CS methods. This study was carried out in a private pathology laboratory located in a metropolitan city, where cytological materials sent from many clinics were examined. MATERIAL AND METHODS: There were 165,915 cases whose smears were examined between 2012 and 2020, most of them conventional (131,224 CS, 34,691 LBC). Cases were evaluated on the basis of the Bethesda 2014 classification and divided into sub-diagnostic categories after they were divided into two main groups as "with epithelial abnormalities" and "without." χ2 and Fischer's precision statistical tests were conducted using SPSS 23.0 package. In the CS process, cervical samples were obtained using an endocervical brush and a spatula. Cells were directly spread onto the slides and promptly fixed in 95% ethanol, followed by staining with the standard Papanicolaou stain. For LBC ThinPrep, cervical specimens were gathered using a cervix brush. The brush was washed in a vial and discarded. Finally, cells were isolated through vacuum filtration and transferred to the slide using air pressure. RESULTS: Squamous cell abnormalities (atypical squamous cells of undetermined significance [ASC-US], atypical squamous cells - cannot exclude high-grade squamous intraepithelial lesion [ASC-H], low-grade squamous intraepithelial lesion [LSIL], high-grade squamous intraepithelial lesion [HSIL], squamous cell carcinoma, atypical glandular cells of undetermined significance) were reported in 5,696 (3.43%) cases. ASC (ASC-US + ASC-H)/SIL ratio (1.36/2.04) was found to be 0.67 (recommended Bethesda ratio is <3). ASC-US (p < 0.001), ASC-H (p < 0.001), and HSIL(p < 0.001) detection rate of LBC was found to be significantly higher than CS. ASC-US (1.8/1.2), ASC-H (0.08/0.008), and HSIL (0.6/0.3) case ratios of LBC/CS were found to be significantly higher in LBC. LSIL (1.72/1.66) rate was similar. CONCLUSION: LBC is superior to CS in detecting epithelial lesions. In addition to being used as a screening method, it is clear that it makes a great contribution to reducing cervical carcinomas due to HPV typing. Definitive comments regarding comparison of methods on reactive changes and microorganism detection are challenging. Preanalytical factors might account for these situations.