Cervical Cancer Screening Program Research Articles

Compliance Rate With Triage Test and Treatment for Participants Screening Positive in Cervical Cancer Screening Programs: A Systematic Review and Meta-analysis.

To assess the rates of adherence to triage testing after positive screening results and referral to treatment for precancerous lesions in global cervical cancer screening programs. We searched three electronic databases (Medline, EMBASE, and Web of Science) for articles published in the English language from January 1, 2018, to December 31, 2023. We included studies reporting the compliance rate of triage testing and precancer treatment in cervical cancer screening programs. ClinicalTrials.gov was reviewed, and no more studies were identified. The combined search strategies identified 1,673 titles, of which 858 titles and abstracts were screened and 113 full-text articles were assessed for eligibility. A total of 33 studies met the inclusion criteria and were included in the meta-analysis. Thirty-three studies were included in the systematic review and meta-analysis. The average compliance rate for women screening positive was 77.1% for triage testing and 69.4% for referral to treatment. Compliance varied by country income level, screening guideline approach, and target population. The current compliance rate was lower than the 90% target set by the World Health Organization's global strategy to eliminate cervical cancer. Inadequate follow-up of participants screening positive revealed a gap between the screening program and clinical care.

Serum levels of stearic and dihomo-γ-linolenic acids can be used to diagnose cervical cancer and cervical intraepithelial neoplasia

Despite widespread cervical cancer (CC) screening programs, low participation has led to high morbidity and mortality rates, especially in developing countries. Because early-stage CC often has no symptoms, a non-invasive and convenient diagnostic method is needed to improve disease detection. In this study, we developed a new approach for differentiating both CC and cervical intraepithelial neoplasia (CIN)2/3, a precancerous lesion, from healthy individuals by exploring CC fatty acid metabolic reprogramming. Analysis of public datasets suggested that various fatty acid metabolizing enzymes were expressed at higher levels in CC tissues than in normal tissues. Correspondingly, 11 free fatty acids (FFAs) showed significantly different serum levels in CC patient samples compared with healthy donor samples. Nine of these 11 FFAs also displayed significant alterations in CIN2/3 patients. We then generated diagnostic models using combinations of these FFAs, with the optimal model including stearic and dihomo-γ-linolenic acids. Receiver operating characteristic curve analyses suggested that this diagnostic model could detect CC and CIN2/3 more accurately than using serum squamous cell carcinoma antigen level. In addition, the diagnostic model using FFAs was able to detect patients regardless of clinical stage or histological type. Overall, the serum FFA diagnostic model developed in this study could be a powerful new tool for the non-invasive early detection of CC and CIN2/3.

Providing a localised cervical cancer screening course for general practice nurses.

Cervical cancer screening programs in Australia have been developed to detect early precancerous changes in women with a cervix aged between 25 and 74. Yet, many barriers remain to the uptake of cervical screening. Barriers include a lack of culturally appropriate service provision, physical access, poor health literacy, emotional difficulties, socio-economic disadvantage and not having access to a female service provider. In remote and very remote areas of Australia, additional barriers experienced by Aboriginal or Torres Strait Islander peoples include a distrust of healthcare providers and a lack of services, resulting in a much higher rate of diagnosis and death from cervical cancer. General practice nurses (GPNs) are well placed to conduct cervical screening tests (CSTs) after they have undertaken additional education and practical training. GPNs' increase in scope of practice is beneficial to general practice as it helps to remove some barriers to cervical screening. In addition, GPNs conducting CSTs reduce GP workload and burnout and increase teamwork. GPNs working in metropolitan clinics have greater access to training facilities, whereas those working in rural and remote clinics are required to travel potentially long distances to complete practical assessments. This highlights the need for training to be made available in rural and remote areas. The aim of this forum paper is therefore to generate further discussion on the need for training programs to be made available in rural and remote areas to aid the upskilling of GPNs.

Assessing knowledge and awareness levels regarding cervical cancer and HPV vaccination in the Jammu regions.

Cervical cancer global burden is highly skewed towards poor countries primarily due to lack of awareness, poor screening, and low uptake of prophylactic vaccines. The purpose of our study is to educate and raise awareness among young girls and women about the importance of cervical screening and HPV vaccination. The present study, conducted from January 2023 to December 2023, focused on students, teachers, housewives, and healthcare professionals in the Jammu region to assess their awareness of cervical cancer and the HPV vaccine. HPV DNA testing was carried out using the Truenat Real-Time PCR method at Swastik Diagnostic Laboratory, Jammu. Knowledge of cervical cancer, awareness of the HPV virus, and the vaccination status of women were assessed in survey. In the HPV screening test, out of 2,400 women, 106 tested positive for HPV. Among these 106 women, 19% had a high viral load (Ct < 20), 11% had a low viral load (25 ≤ Ct < 30), indicating a low relative concentration of HPV viruses, 40% had a medium viral load (20 ≤ Ct < 25), and 30% had very low viral loads (Ct ≥ 30). These findings highlight the importance of routine cervical screenings, such as Pap smears and HPV tests, for the early detection of cervical cancer. There is an urgent need to implement cervical cancer screening and vaccination programs in the Jammu region.

Development and pilot implementation of a novel protocol to assess capacity and readiness of health systems to adopt HPV detection-based cervical cancer screening in Europe

BackgroundCervical 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.MethodsOur 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.ResultsConducted 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.ConclusionsOur 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.

HPV Extended Genotyping to Triage Abnormal Cervical Cancer Screens-Balancing the Harms and Benefits of an Additional Triage Test before Direct Colposcopy Referral.

The Netherlands' cervical cancer screening program transitioned to primary human papillomavirus (HPV) screening in 2017. After the introduction of HPV-based screening, the country saw increases in colposcopy referral rates and detections of low-grade lesions. In July 2022, genotyping was introduced, and those with borderline or mild dyskaryotic (BMD) cytologic abnormalities were only referred to colposcopy if positive for HPV type 16 or 18, and repeat screening otherwise. In this article, various strategies using extended genotyping (HPV16/18/31/33/45/52/58) as a triage test after an abnormal screen were explored using data from HPV-positive participants with normal or BMD cytology in the Population-Based Screening Study Amsterdam (POBASCAM) trial. The authors assessed positive and negative predictive values and colposcopy referral rates for each strategy using extended genotyping to triage women to either direct referral to colposcopy or repeat screening. Direct referral did not meet positive and negative predictive value thresholds for efficiency for any strategies. However, the authors note that direct referral may nonetheless be useful among those with BMD due to minimal increases in colposcopy referrals and concerns of loss to follow-up at repeat screening. These findings demonstrate the potential utility of extended genotyping as a triage test in primary HPV screening programs. The results should be considered alongside the fact that referral to repeat screening may result in loss of engagement of women who need treatment to prevent invasive cancer. See related article by Kroon et al., p. 1037.

HPV self-sampling in organized cervical cancer screening program: A randomized pilot study in Estonia in 2021.

Cervical cancer incidence in Estonia ranks among the highest in Europe, but screening attendance has remained low. This randomized study aimed to evaluate the impact of opt-in and opt-out human papillomavirus (HPV) self-sampling options on participation in organized screening. A random sample of 25,591 women were drawn from the cervical cancer screening target population who were due to receive a reminder in autumn 2021 and thereafter randomly allocated to two equally sized intervention arms (opt-out and opt-in) receiving a choice between HPV self-sampling or clinician sampling. In the opt-out arm, a self-sampler was sent to home address by regular mail; the opt-in arm received an e-mail containing a link to order a self-sampler online. The remaining 30,102 women in the control group received a standard reminder for conventional screening. Participation by intervention arm, age and region of residence was calculated; a questionnaire was used to assess self-sampling user experience. A significant difference in participation was seen between opt-out (41.7%) (19.8% chose self-sampling and 21.9% clinician sampling), opt-in (34.1%) (7.9% self-sampling, 26.2% clinician sampling) and control group (29.0%, clinician sampling only). All age groups and regions in the intervention arms showed higher participation compared to the control group, but the size of the effect varied. Among self-sampling users, 99% agreed that the device was easy to use and only 3.5% preferred future testing at the clinic. Providing women with a choice between self-sampling and clinician sampling significantly increased participation in cervical cancer screening. Opt-in and opt-out options had a different effect across age groups, suggesting the need to adapt strategies.

Challenges regarding the implementation of cervical cancer screening guidelines in Limpopo province, South Africa.

The World Health Organization's (WHO) call to eliminate cervical cancer is essential in improving structures and processes at primary healthcare facilities by galvanising change in providing cervical cancer screening services. The main objective of this study was to explore challenges affecting the implementation of cervical cancer screening guidelines in selected districts in Limpopo Province. The study was carried out at primary health care services (PHCs) in Vhembe and Mopani districts, Limpopo province. Qualitative non-experimental research design of an exploratory, descriptive and contextual nature of a qualitative paradigm to understand cervical cancer screening programme challenges from healthcare professionals' perspectives. The study population comprised two males and 16 female professional registered nurses working in Limpopo province's PHC services. The sample size was 18 professional nurses. A face-to-face interview guided by unstructured questionnaires was undertaken to elicit information regarding the implementation of cervical cancer screening services. Captured data were analysed using Tesch's open-coding method. The study revealed that the cervical cancer guidelines were not effectively implemented as there were contradictions and gaps when applying the guidelines about the management of HIV and AIDS, age restrictions and gestation. Furthermore, structural factors contributed to the inadequacy rate and failure to reach the set targets. Primary health care is an essential health care and human right; therefore, the government should ensure that guidelines and policies are supported financially and that professional nurses are capacitated for the efficient implementation of services.Contribution:Addressing the inequalities in the implementation of social policies for the prevention of cervical cancer prevention and improving the nurses' knowledge and practice behaviour regarding cervical cancer prevention are imperative.

Evaluation of Endocervical Curettage in Colposcopy in the Turkish Cervical Cancer Screening Program.

Background/Objectives: To investigate the risk factors for CIN2+ lesions (cervical intraepithelial neoplasia 3 or worse) in endocervical curettage (ECC) and to evaluate the relationship between the addition of ECC to punch biopsy in terms of the yield of CIN2+ lesions. Methods: Between February 2018 and 2019, data on colposcopy results from 11,944 patients were gathered from the Cancer Department of the Turkish Ministry of Health across the country. A total of 6370 women whom were referred to colposcopy were included in this study. Risk factors were identified using both univariate and multivariate logistic analyses. Results: The median age was 42 years old (range, 30-65). ASC-H (atypical squamous cells-suggestive of high-grade squamous intraepithelial lesion)/HSIL (high-grade intraepithelial lesion) cytology (OR 7.648 95% CI (3.933-14.871)) and HPV (human papillomavirus)-16/18 infection (OR 2.541 95% CI (1.788-3.611)) were identified as risk factors for having CIN2+ lesions. CIN2+ diagnostic yield by ECC is only 1.2% all patients. CIN2+ diagnostic yield by punch biopsy and ECC are 9.7% and 6% of patients, respectively. A higher CIN2+ yield by ECC was observed with increasing age. Among cytology groups, ASC-H/HSIL has highest CIN2+ yield by ECC. Finally, in patients with incomplete visualization of the squamocolumnar junction (SCJ), ECC yields approximately twice as many CIN2+ lesions. Conclusions: ECC should be considered in cases of advanced patient age and in situations where the SCJ is not routinely visualized. In addition, evaluation of the endocervical canal is necessary in HPV-positive cases infected with HPV-16/18 types and in cases infected with HPV of any type but with cytological abnormalities.

Evaluation of Host Gene Methylation as a Triage Test for HPV-Positive Women-A Cohort Study.

This study was designed to evaluate the performance of a host gene methylation marker panel (ASTN1, DLX1, ITGA4, RXFP3, SOX17, and ZNF671) in the triage of human papillomavirus (HPV)-positive women, its possible impact in a cervical cancer screening program, and the possible influence of the variation of the rate of HPV16/18 in its performance. Cohort study in which consecutive women referred for colposcopy in an organized cervical cancer screening program had repeated HPV testing, colposcopy, and biopsies. The women that remained HPV positive at the time of colposcopy were tested with the panel of DNA methylation markers. The performance of the test was evaluated and compared to standard practice. The study test had a sensitivity and specificity for cervical intraepithelial neoplasia (CIN) 2+ of 60.8% (49.1-71.6%) and 88.4% (83.2-92.5%), respectively. For CIN3+, it was of 78.0% (64.0-88.5%) and 86.0% (80.8-90.2%), respectively.The rate and level of methylation positively correlated with the severity of disease. The use of methylation reduces the referral for colposcopy to 25.5%, while detecting 78.0% of the CIN3+ cases. Referral of all HPV16/18-positive cases and triage of the other high-risk HPV-positive cases with methylation, detects 90.0% of the cases of CIN3+, while reducing the number of referrals to 43.2%.The variation in the rate of HPV16/18 does not relevantly affect the performance of the methylation panel. The studied methylation panel has a high sensitivity and specificity for CIN3+ and reduces the rate of referrals for colposcopy, without relevant variation according to the rate of HPV16/18.

Superficial and Invasive Spread of High-grade Squamous Intraepithelial Lesion and Squamous Cell Carcinoma: A Case Report.

We present a case of extensive spread of high-grade squamous intraepithelial lesion (HSIL)/cervical intraepithelial neoplasia grade 3 (CIN3) with foci of invasive squamous cell carcinoma (SCC) in a premenopausal woman. Superficial spread of CIN3 and cervical SCC to the endometrium and/or fallopian tubes is rare, especially in countries with cervical cancer screening programs. Our case occurred during the COVID-19 pandemic, which may have been a major contributing factor to delayed detection and, consequently extensive spread.

The Rare Condition of a Double Cervix: Results from the High-Risk Human Papillomavirus-Based Cervical Cancer Screening Program in the Lazio Region.

Precancerous and cancerous lesions of the uterine cervix are known to be associated with Human Papillomavirus (HPV) infection. The screening of high-risk (HR)-HPV infection in the female population has led to the discovery of several cases of a double cervix, a congenital malformation that is very rare. The purpose of this study was to evaluate HR-HPV infections in women with a double cervix within the National Cervical Cancer Screening program of the Lazio region (Italy). From June 2021 to March 2024, a total of 142,437 samples were analyzed by Seegene's Anyplex TM II HR-HPV method, which identifies 14 HR-HPV genotypes. For each woman identified with a double cervix, two separate samples were taken from both cervices and analyzed separately. Twenty-seven women with a double cervix were identified (0.019%): 23 women were tested as negative for both cervices, while the remaining four (namely A, B, C, and D) resulted positive. By genotyping, the following results were obtained: (A) Both samples showed genotype 31; (B) one cervix was negative while the other showed genotype 58; (C) one cervix was positive for HPV 18 and 31 while for 18, 31, and 33 in the other; and (D) one cervix showed genotype 66 while the other carried the 66 and 68 genotypes. Double cervix is a very rare condition where the presence of HR-HPV genotypes is not homogeneous. As already described, our study confirms that different genotypes can be detected in double cervix malformation, suggesting the need to perform HPV screening on brushing samples from both cervices.

An Implementation Evaluation of the Smartphone-Enhanced Visual Inspection with Acetic Acid (SEVIA) Program for Cervical Cancer Prevention in Urban and Rural Tanzania.

The World Health Organization (WHO) recommends visual inspection with acetic acid (VIA) for cervical cancer screening (CCS) in lower-resource settings; however, quality varies widely, and it is difficult to maintain a well-trained cadre of providers. The Smartphone-Enhanced Visual Inspection with Acetic acid (SEVIA) program was designed to offer secure sharing of cervical images and real-time supportive supervision to health care workers, in order to improve the quality and accuracy of visual assessment of the cervix for treatment. The purpose of this evaluation was to document early learnings from patients, providers, and higher-level program stakeholders, on barriers and enablers to program implementation. From 9 September to 8 December 2016, observational activities and open-ended interviews were conducted with image reviewers (n = 5), providers (n = 17), community mobilizers (n = 14), patients (n = 21), supervisors (n = 4) and implementation partners (n = 5) involved with SEVIA. Sixty-six interviews were conducted at 14 facilities, in all five of the program regions Results SEVIA was found to be a highly regarded tool for the enhancement of CCS services in Northern Tanzania. Acceptability, adoption, appropriateness, feasibility, and coverage of the intervention were highly recognized. It appeared to be an effective means of improving good clinical practice among providers and fit seamlessly into existing roles and processes. Barriers to implementation included network connectivity issues, and community misconceptions and the adoption of CCS more generally. SEVIA is a practical and feasible mobile health intervention and tool that is easily integrated into the National CCS program to enhance the quality of care.

The ESSAG-trial protocol: A randomized controlled trial evaluating the efficacy of offering a self-sampling kit by the GP to reach women underscreened in the routine cervical cancer screening program

BackgroundIn Flanders (Belgium), women not screened for cervical cancer (CC) within the last three years receive an invitation letter from the regional screening organization, the Centre for Cancer Detection (CCD), encouraging them to have a cervical specimen taken by their general practitioner (GP) or gynecologist. However, the coverage for CC screening remains suboptimal (63%). The offer of a self-sampling kit (SSK, for HPV testing) by a GP may trigger participation among women who do not attend regular screening. MethodsThe ESSAG-trial is a cluster-randomized controlled trial with three arms, each including 1125 women aged 31–64 years, who were not screened for CC in the last 6 years. In arm A, GPs offer a SSK when eligible women consult for any reason. In arm B, women receive a personal GP signed invitation letter including an SSK at their home address. In the control arm, women receive the standard invitation letter from the CCD. The primary outcome is the response rate at three months after inclusion. Secondary outcomes are: screen test positivity; compliance with foreseen follow-up among screen-positives; costs per invited and per screened women; as well as contrasts between trial arms and between socio-demographic categories. ConclusionThe ESSAG-trial will assess the effect of GP-based interventions using SSKs on CC screening participation among hard-to-reach populations. Findings will inform policymakers about feasible strategies on increasing CC screening that may be rolled-out throughout the whole region. Trial registrationClinicalTrials.gov: NCT05656976

High-risk HPV Prevalence Estimates among Older Patients: Implications for Cervical Cancer Screening Programs.

Due to the heterogeneity of existing studies and wide range of human papilloma virus (HPV) prevalence in India, further research into the incidence of HR-HPV and its spectrum of genotypes is essential to develop screening policies. This study aimed to determine the incidence and demographic distribution of HR-HPV among cisgender female patients attending a tertiary care facility in North India. This study was conducted in the Department of Obstetrics and Gynaecology, SGRR Institute of Medical and Health Sciences, Dehradun, India. HPV-DNA test results of 653 female patients were assessed for HR-HPV positivity, genotyping, and age-based differences via Chi-square analysis. Overall prevalence of HR-HPV was 4.90%, HPV-16 was 1.37%, HPV-18 was 0.76%, and HPV non-16,18 was 2.7%. In patients ≤ 50 years, prevalence of HPV-16 was 0.97%, HPV-18 was 0.38%, and HR-HPV non-16,18 was 2.71%. In patients > 50 years, prevalence of HPV-16 was 2.89%, HPV-18 was 2.17%, and HR-HPV non-16,18 was 2.89%. The difference in the prevalence of HPV-16,18 between patients ≤ and > 50 years was found to be highly statistically significant (P = 0.007485). The difference in the prevalence of total HR-HPV between patients ≤ and > 50 years was not found to be statistically significant (P = 0.059905). Our study's finding of higher HR-HPV positivity rates in patients > 50 years emphasizes the need for continued HR-HPV-DNA-based screening of this cohort. With widespread use in post-menopausal patients, HPV screening can serve as an important armamentarium in the fight against cervical cancer.

Cervical cancer screening integrated in routine clinical care of women with HIV.

To evaluate if integrated cervical cancer screening (CCS) for women with HIV (WWH) in routine HIV care resulted in increased adherence to screening, and to describe the prevalence of human papillomavirus (HPV)-specific genotypes and the incidence of cellular abnormalities. Cohort study. WWH who accepted the offer of combined CCS and HIV care (group 1), WWH who declined the offer (group 2), and WWH not offered CCS within HIV care (group 3) between 2013 and 2019 were included. Data was collected from The Danish HIV Cohort Study and The Danish Pathology Data Bank. Adherence to the CCS program was defined as fulfilled if WWH were screened annually. A total of 804 WWH were included. WWH who accepted CCS within HIV care (group 1; n = 218) had significantly higher adherence to screening in all study years 22-99% compared with the WWH who declined CCS (group 2; n = 232) 10-16% and WWH who were not invited for CCS (group 3; n = 354) 11-25%. There was no significant difference in the prevalence of HPV-specific genotypes and incidence of cellular abnormalities among the three groups. Integrating CCS for WWH in routine HIV care resulted in higher adherence to the CCS guidelines. Combined services thereby represent an opportunity to engage WWH in HIV care into preventive services.

Retrospective Cross-Sectional Epidemiological Study of Human Papillomavirus-Associated Precancers and Anogenital Warts in Patients Attending Specialized Clinics in Russian Federation

Background. In Russia, there are no country level registries on HPV-associated pre-cancers (cervical intraepithelial neoplasia, CIN; vulvar intraepithelial neoplasia, VIN; vaginal intraepithelial neoplasia, VaIN; anal intraepithelial neoplasia, AIN; penile intraepithelial neoplasia PIN) and anogenital warts (AWs) and no national-level cervical cancer screening program. Aims — the aim of this study was to assess the proportion of patients with CIN, VIN, VaIN, AIN, PIN and AWs diagnosis in the clinical settings in Russia. Methods. This study was a non-interventional retrospective multi-center chart-review study in 28 investigational sites representing 21 Federal subjects of 6 Federal Districts of Russia. Medical charts of adult men and women visited gynecology, sexual health, dermatovenerology or urology services between 1 Jan 2000 — 31 Dec 2019 were reviewed. Data were abstracted, using a standardized approach, on patient demographic characteristics, presence or absence of pre-cancers and AWs diagnoses, method of diagnosing pre-cancer and HPV infection, and grade of neoplasia. Results. A total of 11 520 patients (1732 male and 9788 female) were included in the analysis. The overall proportion of patients with HPV-associated precancers and AWs was 10.8%. By service type, cases of HPV-associated conditions were revealed most often in dermatological departments (14.5%) and gynecological hospitals (13.8%). CIN detection rate in Russian clinical settings increased over the 20-years from 3.2 to 11.1% and was higher in gynecological in-patient departments compared to out-patient departments (12.5 and 5.2% respectively). The number of non-cervical precancers (VIN, VaIN, AIN, PIN) cases were very low (the detection rate was less than 1%). The frequency of HPV type 16 and 18 detection increased from 0.6 to 4.8%, and from 0.2 to 1.9%, respectively, for the 20-years period. Conclusions. Our study suggested high level of HPV-related pre-cancer and AW disease burden as well as presence of high-risk HPV types. Preventive strategy through effective national HPV immunization program would be beneficial to reduce HPV-related disease burden in Russia.

Risk of cervical high-grade squamous intraepithelial neoplasia in cytologic negative and persistently high-risk human papillomavirus positive patients according to genotypes: a retrospective single center analysis

In January 2020, a different cervical cancer screening program started in Germany. Women above the age of 35 are recommended to have a combined HPV and cytology swab every three years. Showing persistent high-risk human papillomavirus (hrHPV), cytologic negative cervical samples at baseline and after 12 months, patients are referred to colposcopy. Entailing considerable additional workload due to the required colposcopies, we analyzed the risk of high-grade cervical intraepithelial neoplasia (CIN 3) in cytologic negative and persistent hrHPV women according to their hrHPV genotypes.Methods In this single center retrospective study, patients with persistent hrHPV, cytology negative cervical samples from our certified Colposcopy Unit in 2020 and 2021 were analyzed. Patient demographics, hrHPV types, biopsy rates and histological reports were collected.Results During the study, 69 patients were enrolled. Most frequent hrHPV genotypes were: hrHPV other 72.5%; HPV 16, 20.3% and HPV 18, 7.2%. Colposcopy showed no or minor changes in 92.7% and major changes in 7.2%. CIN 3 was found in 7 patients (10.1%). Prevalence of CIN 3 by hrHPV genotypes was 27.3% for HPV16, 20.0% for HPV18 and 7.1% for HPVO. A statistically significant dependency between hrHPV and cervical intraepithelial neoplasia was demonstrated (p = 0.048).Conclusion Within this single center study of persistent hrHPV, cytologic negative samples, patients with HPV 16 were more likely to have high-grade disease compared to other hrHPV subtypes. Larger prospective randomized trials are needed to substantiate our results and obtain adjusted cervical cancer screening time intervals according to the hrHPV genotypes.

Coverage and Socioeconomic Inequalities in Cervical Cancer Screening in Low- and Middle-Income Countries Between 2010 and 2019.

Cervical cancer screening is vital in addressing the global burden of cervical cancer. In this study, we describe the coverage and socioeconomic inequalities in the coverage of cervical cancer screening in low- and middle-income countries (LMICs). We analyzed data from the women's recode files of the Demographic and Health Surveys conducted in LMICs from 2010 to 2019 with variables on cervical cancer screening. We included women 21 years or older and determined the proportion of women who were screened for cervical cancer by age categories, wealth quintile, type of place of residence, level of education, and marital status. Socioeconomic inequality was measured using the concentration index (CIX) and the slope index of inequality (SII). A total of 269,506 women from 20 surveys in 16 countries were included in the survey. Generally, there was a low coverage of screening, with lower rates among women age 21-24 years, living in rural areas, in the poorest wealth quintile, with no formal education, and who have never been in union with or lived with a man. The CIX and SII values for screening for cervical cancer were positive (pro-rich) for all the countries except Tajikistan in 2012 where they were negative (pro-poor). The coverage of cervical cancer screening was low in LMICs with variations by the quintile of wealth (pro-rich) and type of place of residence (pro-urban). To achieve the desired impact of cervical cancer screening services in LMICs, the coverage of cervical cancer screening programs must include women irrespective of the type of place and wealth quintiles.

Low methylation marker levels among human papillomavirus-vaccinated women with cervical high-grade squamous intraepithelial lesions.

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