Partha Basu

Cervical intraepithelial neoplasia progression and regression among women living with HIV in Zambia

Abstract Objectives Cervical screening and precancer treatment are less effective in women living with HIV (WLWH) than in women without HIV. We assessed high‐risk human papillomavirus (HR‐HPV) infection and cervical disease progression among screened WLWH in Zambia. Methods Participants underwent visual inspection with acetic acid (VIA), HR‐HPV testing and cervical biopsies at baseline and at follow‐up 30–36 months later. Women with positive VIA results or high‐grade histology were offered treatment. We assessed HR‐HPV and cervical disease prevalence at both timepoints and used multivariable logistic regression to identify factors associated with cervical disease progression and regression. Results Among 241 included women, HR‐HPV prevalence declined from 44% (95% confidence interval [CI]: 39%–49%) at baseline to 24% (95% CI: 19%–31%) at follow‐up. High‐grade disease decreased from 25% (95% CI: 20%–31%) to 9% (95% CI: 5%–13%). In analyses adjusted for age, CD4 cell count, HIV RNA viral load, HR‐HPV infection and histological results at baseline, precancer treatment was associated with increased odds of disease regression (adjusted odds ratio [aOR]: 2.74, 95% CI: 1.08–7.06) and reduced odds of progression (aOR: 0.45, 95% CI: 0.11–1.64). One‐third of women with high‐grade disease at follow‐up (7/21) had previously undergone precancer treatment. Conclusions Cervical screening and precancer treatment are key to reducing cervical disease progression among WLWH and ultimately achieving cervical cancer elimination, but efforts to improve treatment effectiveness among WLWH must be balanced with the risk of overtreatment.

Comparative efficacy, feasibility and acceptability of HPV DNA testing on first-void urine versus self-collected vaginal samples: a real-world study in a resource-limited setting

Introduction Self-sampling for cervical cancer screening is a promising strategy to improve coverage and reduce strain on health systems. First-void urine (FVU) has emerged as a non-invasive alternative to self-collected vaginal samples for detecting high-risk human papillomavirus (HPV). However, most supporting evidence is from colposcopy clinic settings and not from screening settings. This community-based study in Eastern India aimed to (1) assess agreement between HPV testing on FVU and vaginal samples, (2) compare their accuracy in detecting cervical intraepithelial neoplasia grade 2 (CIN2+) lesions and (3) evaluate feasibility and acceptability in a resource-limited setting. Methods At multiple rural clinics, 2500 women aged 30–60 years provided both FVU and self-collected vaginal samples. All samples were tested centrally using the Cobas4800 assay; discordant results were retested with the Allplex HR-HPV assay. HPV-positive women were referred for colposcopy and biopsy. Acceptability and preference were assessed through structured surveys with 1500 women and focus group discussions with health workers. These health workers counselled women at the clinics to provide both self-collected samples. Results All participants provided satisfactory samples, except for two FVU samples, which did not yield satisfactory test results on repeated analysis. Agreement between FVU and vaginal samples for HPV detection was 99.0% (κ=0.90), with high concordance for HPV 16/18 (κ=0.90). CIN2+ detection rates were 6.0 and 7.2 per 1000 women screened with FVU and vaginal samples, respectively (p=0.6), with no statistically significant difference in sensitivity. Among surveyed women, 98.1% preferred urine sampling. Health workers favoured both self-sampling methods over speculum-based clinician collection. Conclusion HPV testing using FVU demonstrates high agreement with vaginal self-sampling, comparable accuracy in detecting CIN2+ lesions and greater acceptability among women. This method is feasible and well-suited for cervical cancer screening in resource-limited settings.

Leveraging single-dose human papillomavirus vaccination dose-efficiency to attain cervical cancer elimination in resource-constrained settings

Abstract Background In low- and middle-income countries, resource constraints remain a critical factor limiting access to cervical cancer preventive measures. The option of single-dose immunization could help improve access to human papillomavirus vaccination and attain cervical cancer elimination. Methods With simulation models adapted to country-specific data and scenarios for single-dose protection derived from International Agency for Research on Cancer India vaccine trial data, we estimated the expected impact of single-dose vaccination in India, Rwanda, and Brazil, three countries with varying profiles of cervical cancer risk and vaccination timelines. In combination with single-dose vaccination, we explored different resource reallocation strategies based on dose efficiency, elimination attainment, and cervical cancer cases prevented, with the existing 2-dose program as a comparator. Results Assuming lifelong single-dose protection, switching from 2-dose to 1-dose vaccination and reallocating resources to female catch-up could prevent 467-1336, 94-194, and 15-207 additional cervical cancer cases (per 100 000 women born) in cohorts aged 11-30 years in India, Rwanda, and Brazil, respectively. Resource reallocation to improve the current routine coverage could help eliminate cervical cancer in India and across all Brazilian states but not in Rwanda. For each country, we found a dose-efficient reallocation strategy (or a combination of strategies) together with 1-dose vaccination that could prevent more cervical cancers vs 2-dose vaccination, even in the worst-case scenario of single-dose protection. Conclusion Adopting single-dose vaccination with resource reallocation is a resource-efficient approach to enhance progress toward cervical cancer elimination. The overall impact of vaccination can be maximized by fine-tuning resource reallocation to a country’s needs.

Creating a data processing warehouse to support performance monitoring of cancer screening programmes in Europe using a common set of indicators

Abstract The CanScreen-ECIS project implemented by International Agency for Research on Cancer aimed to define indicators to monitor, breast, cervical, colorectal, and lung cancer screening and create a validated mechanism for the European screening programmes to be able to systematically collect and submit performance data for public dissemination through European Cancer Information System (ECIS). Indicators were developed through a stepwise process of literature review, Delphi survey followed by face-to-face interaction. A survey questionnaire to report policies, protocols, and organization of screening programmes and a data collection tool to estimate indicators across the screening continuum were designed. These were integrated into a data warehouse to permit programme managers to access the tools, undergo training, submit data, and estimate the indicators. The same warehouse would allow peer-reviewing of submitted information and data and will ultimately be connected to ECIS for data visualization. Functionalities of the tools and the warehouse were pilot tested through data collection from several European countries. Total 23 indicators were selected based on priority and feasibility. Programme managers from 23 European countries completed the surveys and submitted data from national/regional screening programmes. Data to estimate the indicators were obtained from 17, 13, and 15 breast, cervical, and colorectal cancer screening programmes, respectively. Major challenges identified by the participants included collecting data from opportunistic screening and data disaggregated by socio-economic status and other indicators of inequalities. The data warehouse will facilitate systematic data collection to report the status and performance of cancer screening programmes in the EU.

Use of Thermal Ablation in Low-Resource Settings: Experience From Three Multicenter Noninferiority Randomized Clinical Trials

PURPOSE Thermal ablation (TA) is now a widely used treatment for cervical precancer in low- and middle-income countries. Over the past decade, TA devices have been redesigned to be more portable, user-friendly, and affordable. This analysis combines data from three large randomized clinical trials comparing the efficacy, safety, and acceptability of TA with those of the previous standard, gas-based cryotherapy. METHODS This analysis used Human Papillomavirus (HPV) test results at 1-year post-treatment as the primary outcome. Secondary outcomes included side effects and patient satisfaction. RESULTS Of the 2,948 participants treated with either TA or gas-based cryotherapy, 80.9% and 81.8% completed HPV testing at 1 year, respectively. Overall, 60.7% tested negative for HPV at follow-up, with slightly higher rates in the TA group (62.5%) compared with cryotherapy (58.7%), although the difference was not statistically significant ( P value = .14). Side effects were minimal for both treatments. Severe pain was slightly more common with TA (7.6% v 3.9% for cryotherapy), but vasovagal responses were less frequent (2.3% v 7.6%). Satisfaction with treatment was high (approximately 98%) across both groups. CONCLUSION Our findings support the efficacy of TA in treating cervical precancer, offering an effective and practical alternative in low-resource settings. However, future research is urgently needed to address critical questions, including the standardization of treatment protocols and tailored approaches for women living with HIV.

Technical, legal and ethical framework of cancer audit in cervical screening – Summary of best practices for organised programmes delineated through an expert group consultation

AbstractEfficient and well‐organised cervical screening programmes have significantly reduced both the incidence and mortality rates of cervical cancer in the population. For optimal performance, such programmes need to incorporate essential quality assurance measures. The International Agency for Research on Cancer (IARC/WHO) organised an expert consultation to delineate best practices in auditing cancers in a cervical screening programme, the legal and ethical frameworks governing such audits, and communicating audit outcomes. As a best practice, every programme should have a well‐documented policy and process framework for cancer audits. The TWGs agreed that the primary goal of programmatic cancer audits is to assess the programme's effectiveness in lowering cervical cancer incidence and minimising screening‐related risks. Using audit results, informed decisions can be made to enhance service delivery, including professional training, adopting improved screening tests, strengthening fail‐safe mechanisms, reducing delays, and minimising inequalities. Legal complexities in cervical screening stem from its inherent limitations and risks, and differentiating cases of negligence from inevitable and non‐negligent errors where an abnormality is not detected but actually exists is crucial. TWGs suggested that determining whether a screening error was serious enough to be categorised as negligent and/or to entitle the patient to compensation should reflect the inherent limitations of cervical screening. Data obtained while performing screening tests and subsequent diagnostic tests or treatments are sensitive and need to be safeguarded. The best practice document drafted through expert consultation will help cervical screening programmes standardise practices related to cancer audits and address associated legal and ethical issues.

Analysis of time trends of prevalence of high-risk HPV infections, high grade cervical precancer and cervical cancer disease in women from Eastern India over 20 years − Pooled analysis from three studies

Cervical cancer remains a leading cause of cancer related morbidity and mortality among women worldwide, particularly in low-and middle- income countries (LMICs). The incidence of cervical cancer has declined in India over the last two decades despite the lack of any organised population-based screening programme or HPV vaccination. This study analyses the trends in high-risk human papilloma virus (hrHPV) prevalence and CIN 2 + detection and examines the influence of sociodemographic factors in West Bengal, India from over a span of two decades. Data from three cervical cancer screening studies conducted in rural West Bengal were analysed between 2001 and 2021. A total of 80,988 women aged 30-60 years were screened using Hybrid Capture II© (HC II) test. Detection rates of CIN 2 + were stratified by age, education and marriage. Logistic regression models were used to identify factors influencing high risk HPV positivity and CIN 2 + prevalence. The overall high risk HPV positivity rate remained relatively stable (5 %) across the study periods with no significant difference between self-collected and provider collected samples. However, CIN 2 + detection rates declined significantly from 5.7/1000 in 2001-2003 to 2/1000 in 2018-2021 (adjusted odds ratio [OR]:0.27; 95 % confidence interval [CI]:0.12-0.46). Higher education (OR: 0.64; 95 % CI: 0.45-0.88) and delayed age at marriage (OR: 0.62; 95 %CI: 0.31-1 for age>21) were associated with lower CIN 2 + risk. The findings of the study indicate that the observed decline in CIN 2 + prevalence in West Bengal can be attributed to improved education, delayed age at marriage, reduced fertility rate and women's empowerment, which can explain the gradual reduction in cervical cancer incidence in India. However, the cervical cancer incidence in India remains above WHO elimination targets. Expedited implementation of HPV vaccination and strengthening screening programmes are necessary to sustain and accelerate progress towards elimination of cervical cancer.

Artificial intelligence strengthenes cervical cancer screening – present and future

Cervical cancer is a severe threat to women’s health. The majority of cervical cancer cases occur in developing countries. The WHO has proposed screening 70% of women with high-performance tests between 35 and 45 years of age by 2030 to accelerate the elimination of cervical cancer. Due to an inadequate health infrastructure and organized screening strategy, most low- and middle-income countries are still far from achieving this goal. As part of the efforts to increase performance of cervical cancer screening, it is necessary to investigate the most accurate, efficient, and effective methods and strategies. Artificial intelligence (AI) is rapidly expanding its application in cancer screening and diagnosis and deep learning algorithms have offered human-like interpretation capabilities on various medical images. AI will soon have a more significant role in improving the implementation of cervical cancer screening, management, and follow-up. This review aims to report the state of AI with respect to cervical cancer screening. We discuss the primary AI applications and development of AI technology for image recognition applied to detection of abnormal cytology and cervical neoplastic diseases, as well as the challenges that we anticipate in the future.

A portable thermal ablation device for cervical cancer prevention in a screen-and-treat setting: a randomized, noninferiority trial

AbstractImplementing standard-of-care cryotherapy or electrosurgical excision to treat cervical precancers is challenging in resource-limited settings. An affordable technological alternative that is as effective as standard-of-care techniques would greatly improve access to treatment. This randomized controlled trial aims to demonstrate the noninferiority efficacy of a portable, battery-driven thermal ablation (TA) device compared to cryotherapy and electrosurgical excision (large loop excision of transformation zone (LLETZ)) to treat cervical precancer in a screen-and-treat program in Zambia. A total of 3,124 women positive on visual inspection with acetic acid and eligible for ablative therapy were randomized to one of the treatment arms. Human papillomavirus (HPV) testing was performed at baseline and at the follow-up. The primary outcome was treatment success, defined as either type-specific HPV clearance at the follow-up in participants positive for HPV at baseline, or a negative visual inspection with acetic acid test for those who had a negative HPV test at baseline. After a median follow-up of 12 months, treatment success rates were 74.0%, 71.1% and 71.4% for the TA, cryotherapy and LLETZ arms, respectively, thus demonstrating noninferiority (P = 0.83). TA was a safe and well-accepted procedure. Only 3.6% of those randomized to TA reported moderate-to-severe pain, compared to 6.5% and 1.9% for the cryotherapy and LLETZ arms, respectively. Thus, our randomized controlled trial demonstrates the safety and efficacy of TA, which is not inferior to cryotherapy or surgical excision.ClinicalTrials.gov registration: NCT02956239.

Efficacy of point‐of‐care thermal ablation among high‐risk human papillomavirus positive women in China

AbstractThermal ablation is a point‐of‐care ablative treatment technique for cervical intraepithelial neoplasia (CIN). However, limited information is available about its efficacy in low‐ and middle‐income countries. We evaluated the efficacy of thermal ablation in treatment of CIN detected through high‐risk human papillomavirus (HPV) screening in China. Women positive on high‐risk HPV and having colposcopically suspected lesions eligible for ablation underwent colposcopy, biopsy and thermal ablation in one visit. Women ineligible were recalled for large loop excision of transformation zone (LLETZ) when histopathology results were high‐grade CIN. Posttreatment follow‐up at 6 months or more was with HPV test and cytology followed by colposcopy and biopsy for HPV and/or cytology‐positive women. Cure was defined as either negative cytology and HPV test or absence of histopathology proved CIN in any positive women. Of total 218 HPV‐positive women treated with thermal ablation (n = 170) or LLETZ (n = 48), 196 reported for follow‐up evaluation. For women with histologically confirmed CIN at baseline (thermal ablation‐104; LLETZ‐38), cure rates were 84.6% for thermal ablation and 86.8% for LLETZ. Cure rates after thermal ablation were 90.3% for CIN grade one (CIN1) and 76.2% for CIN grade two or worse (CIN2+). HPV clearance rate was 80.4% in women undergoing thermal ablation, which was lower for HPV16/18 compared to other oncogenic types (67.6% vs 85.7%). HPV test had a negative predictive value (NPV) of 98.7% to detect CIN2+ at follow‐up and the positive predictive value (PPV) was 40.4%. Thermal ablation is effective to treat CIN as well as to clear the high‐risk HPV infection. HPV test has high PPV and NPV in following up patients posttreatment.

The European response to the WHO call to eliminate cervical cancer as a public health problem

AbstractThe age‐standardised incidence of cervical cancer in Europe varies widely by country (between 3 and 25/100000 women‐years) in 2018. Human papillomavirus (HPV) vaccine coverage is low in countries with the highest incidence and screening performance is heterogeneous among European countries. A broad group of delegates of scientific professional societies and cancer organisations endorse the principles of the WHO call to eliminate cervical cancer as a public health problem, also in Europe. All European nations should, by 2030, reach at least 90% HPV vaccine coverage among girls by the age of 15 years and also boys, if cost‐effective; they should introduce organised population‐based HPV‐based screening and achieve 70% of screening coverage in the target age group, providing also HPV testing on self‐samples for nonscreened or underscreened women; and to manage 90% of screen‐positive women. To guide member states, a group of scientific professional societies and cancer organisations engage to assist in the rollout of a series of concerted evidence‐based actions. European health authorities are requested to mandate a group of experts to develop the third edition of European Guidelines for Quality Assurance of Cervical Cancer prevention based on integrated HPV vaccination and screening and to monitor the progress towards the elimination goal. The occurrence of the COVID‐19 pandemic, having interrupted prevention activities temporarily, should not deviate stakeholders from this ambition. In the immediate postepidemic phase, health professionals should focus on high‐risk women and adhere to cost‐effective policies including self‐sampling.

Comparative performance evaluation of different HPV tests and triaging strategies using self‐samples and feasibility assessment of thermal ablation in ‘colposcopy and treat’ approach: A population‐based study in rural China

Human papillomavirus (HPV) test, self‐sampling and thermal ablation for cervical intraepithelial neoplasia (CIN) have been developed separately to increase screening coverage and treatment compliance of cervical cancer screening programmes. A large‐scale study in rural China screened 9,526 women with their combinations to explore the optimal cervical cancer‐screening cascade in the real‐world. Participants received careHPV and polymerase chain reaction (PCR) HPV tests on self‐collected samples. Women positive on either HPV test underwent colposcopy, biopsy and thermal ablation in a single visit. Samples positive on either HPV test were retested for genotyping. Absolute and relative performance of HPV tests, triage strategies, ‘colposcopy and thermal ablation’ approach were statistically evaluated. PCR HPV test detected 33.3% more CIN grade two or worse (CIN2+) at a cost of 28.1% more colposcopies compared to careHPV. Sensitivities of PCR HPV and careHPV tests to detect CIN2+ were 96.7 and 72.5%. Specificities for the same disease outcome were 82.1 and 86.0%. Triaging HPV‐positive women with HPV16/18 genotyping considerably improved the positive predictive value for CIN2+ (4.8–5.0 to 18.2–19.2%). Ninety‐six women positive on HPV and having abnormal colposcopy were eligible for thermal ablation and all accepted same‐day treatment, contributing to 64.6% being treated appropriately (CIN1+ on histopathology), which reached up to 84.8% among women positive on HPV 16/18 triage. No serious side‐effects/complications were reported. The combination of PCR HPV test followed by HPV 16/18 triaging on self‐collected samples and colposcopy of triage positive women followed by immediate thermal ablation might be the appropriate screening cascade for rural China.

Cancer Screening in the Coronavirus Pandemic Era: Adjusting to a New Situation

PURPOSE The coronavirus-induced pandemic has put great pressure on health systems worldwide. Nonemergency health services, such as cancer screening, have been scaled down or withheld as a result of travel restrictions and resources being redirected to manage the pandemic. The present article discusses the challenges to cancer screening implementation in the pandemic environment, suggesting ways to optimize services for breast, cervical, and colorectal cancer screening. METHODS The manuscript was drafted by a team of public health specialists with expertise in implementation and monitoring of cancer screening. A scoping review of literature revealed the lack of comprehensive guidance on continuation of cancer screening in the midst of waxing and waning of infection. The recommendations in the present article were based on the advisories issued by different health agencies and professional bodies and the authors' understanding of the best practices to maintain quality-assured cancer screening. RESULTS A well-coordinated approach is required to ensure that essential health services such as cancer management are maintained and elective services are not threatened, especially because of resource constraints. In the context of cancer screening, a few changes in invitation strategies, screening and management protocols and program governance need to be considered to fit into the new normal situation. Restoring public trust in providing efficient and safe services should be one of the key mandates for screening program reorganization. This may be a good opportunity to introduce innovations (eg, telehealth) and consider de-implementing non–evidence-based practices. It is necessary to consider increased spending on primary health care and incorporating screening services in basic health package. CONCLUSION The article provides guidance on reorganization of screening policies, governance, implementation, and program monitoring.

Triage performance and predictive value of the human gene methylation panel among women positive on self‐collected HPV test: Results from a prospective cohort study

AbstractTriaging of women positive for high‐risk human papillomavirus (hrHPV) on self‐collected samples requires a molecular reflex test to avoid recall for cytology or visual tests. We assessed triage performance and predictive value of human gene methylation panel (ZNF671/ASTN1/ITGA4/RXFP3/SOX17/DLX1) alone and with combination of HPV16/18 genotyping in a longitudinal screening study. Out of 9526 women at baseline, 1758 women positive for hrHPV on self‐collected samples followed up yearly were included in the current analysis. Satisfactory risk stratification to detect cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was demonstrated by the methylation panel with an odds ratio (OR) of 11.3 among methylation‐positive women compared to methylation‐negative counterparts. Triaging with methylation panel reduced colposcopy referral rate by 67.2% with sensitivity and specificity of 83.0% and 69.9% to detect CIN2+. The corresponding values for the combining methylation and HPV 16/18 were 96.6% and 58.3%. The cumulative 3‐year incident CIN2+ risk was 6.8% (95% CI: 4.9%‐8.6%) for hrHPV positive women, which was reduced to 4.5% (95% CI: 2.7%‐6.3%) and 2.9% (95% CI: 1.2%‐4.5%) for women negative on methylation triaging alone and negative on the combined strategy. The corresponding risk for women positive for both methylation and HPV 16/18 reached 33.7% (95% CI: 19.0%‐45.8%). Our study demonstrated the satisfactory triage performance and predictive value of the methylation panel, especially in combination with HPV 16/18 genotyping. The substantially lower risk of CIN2+ among the triage negative women over the next 3 years suggests that the interval for repeat HPV test can be safely extended to at least 2 years.

A Study of the Impact and Restitutive Efforts of Cervical Cancer Screening during the COVID-19 Pandemic in a Regionsl Cancer Centre in Eastern India

To evaluate the feasibility and efficacy of switching to a self-sampling based screening as compared to ongoing provider-collection based screening using HPV DNA test and assess the compliance of HPV positive women for further treatment during the COVID 19 pandemic. The study participants were women aged 30-60 years from rural and semi-urban communities around Kolkata, who underwent screening followed by HPV testing by Hybrid Capture II test. In the pre pandemic era, the women who attended the health centres where trained health workers that collected cervical samples. Following lockdown, the health workers distributed the self-sampling device to the women during home visits and counselled them to collect their samples by themselves. Thereafter the self collected screened positive women were brought to the hospital for further treatment instead of community clinics. From April 2018 to March 2020, 12,718 women underwent screening using either HPV DNA test or visual inspection with acetic acid. HPV samples were either provider collected (62.7%) or self-collected (37.2%). The HPV positivity and CIN2+ detection rate were 5.4% and 2%. From April 2020 to February 2022, 10,792 women underwent screening using self-sampling only. The HPV positivity rate and CIN2+ detection rate were found to be 5.1% and 1.9 % . Cervical cancer screening by HPV self-sampling advocates participation of more women especially in rural areas, while accelerating progress towards elimination of cervical cancer.

Efficacy and safety of therapeutic HPV vaccines to treat CIN 2/CIN 3 lesions: a systematic review and meta-analysis of phase II/III clinical trials

Objectives We aim to assess the efficacy and safety of therapeutic human papillomavirus (HPV) vaccines to treat cervical intraepithelial neoplasia of grade 2 or 3 (CIN 2/3). Design Systematic review and meta-analysis, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations. Data sources PubMed, Embase, Web of Science, Global Index Medicus and CENTRAL Cochrane were searched up to 31 January 2022. Eligibility criteria Phase II/III randomised controlled trials (RCTs) and single-arm studies reporting the efficacy of therapeutic vaccines to achieve regression of CIN 2/3 lesions were included. Studies evaluating only safety and side effects of the vaccine were excluded. Data extraction and synthesis Two independent reviewers extracted data and evaluated study quality. A random-effect model was used to pool the proportions of regression and/or HPV clearance. Results 12 trials met the inclusion criteria. Out of 734 women (all studies considered) receiving therapeutic HPV vaccine for CIN 2/3, 414 regressed to normal/CIN 1 with an overall proportion of regression of 0.54 (95% CI 0.39 to 0.69) for vaccinated group; 166 women (from five RCTs) receiving placebo only achieving a pooled normal/CIN 1 regression of 0.27 (95% CI 0.20 to 0.34). When including only the five two-arm studies, the regression proportion for the 410 vaccine group participants was higher than that of the 166 control group participants (relative risk (RR) 1.52; 95% CI 1.14 to 2.04). The pooled proportion of high-risk human papillomavirus (hrHPV) clearance was 0.42 (95% CI 0.32 to 0.52) in the vaccine group (six studies with a total of 357 participants) and 0.17 (95% CI 0.11 to 0.26) in the control group (three RCTs with a total of 104 participants). Based on these three RCTs, the hrHPV clearance was significantly higher in the vaccinated group (250 participants) compared with the control group (RR 2.03; 95% CI 1.30 to 3.16). Similar results were found regarding HPV 16/18 clearance. No significant unsolicited adverse events have been consistently reported. Conclusions The efficacy of the therapeutic vaccines in the treatment of CIN 2/3 was modest. Implementation issues such as feasibility, acceptability, adoption and cost-effectiveness need to be further studied. PROSPERO registration number CRD42022307418.

Agreement between Self- and Physician‑Sampling for Detection of High‑Risk Human Papillomavirus Infections in Women Attending Cervical Screening at National Cancer Institute, Thailand

We determined testing of self-sampling vagina swabs for Human Papilloma Virus (HPV) can be used to screen for cervical disease in outpatient clinics. In this study, women attending cervical cancer screening clinic and gynecology clinic of the National Cancer Institute were invited to take a vaginal self-sampling and physician-collected cervical sampling. Of 268 participants, 20 (7.5%) were HPV-positive on the physician-collected samples. Among these screen-positive women, only two (0.7%) had HPV 18 and/or 45 and none had HPV 16 infections. For the self-collected samples, 4 participants had invalid HPV test results. Of the remaining 264 women with valid test results on self-collected samples, 29 (11.0 %) were HPV-positive, of whom, two (0.8%) were infected with HPV 16 and one (0.4%) with HPV 18 and/or 45 infections. The agreement between self-sampling and physician-sampling HPV test results (when two HPV results categories were considered) was 92. 8% with a moderate Kappa value of 0.57. Overall, self-sampling seems to be a reliable alternative to health-provider collection. However, instructions on proper procedures for sample collection to the women are important step before general roll out.

Building resilient cervical cancer prevention through gender-neutral HPV vaccination

The COVID-19 pandemic has disrupted HPV vaccination programmes worldwide. Using an agent-based model, EpiMetHeos, recently calibrated to Indian data, we illustrate how shifting from a girls-only (GO) to a gender-neutral (GN) vaccination strategy could improve the resilience of cervical cancer prevention against disruption of HPV vaccination. In the base case of 5-year disruption with no coverage, shifting from GO to GN strategy under 60% coverage (before disruption) would increase the resilience, in terms of cervical cancer cases still prevented in the disrupted birth cohorts per 100,000 girls born, by 2.8-fold from 107 to 302 cases, and by 2.2-fold from 209 to 464 cases under 90% coverage. Furthermore, shifting to GN vaccination helped in reaching the World Health Organization (WHO) elimination threshold. Under GO vaccination with 60% coverage, the age-standardised incidence rate of cervical cancer in India in the long term with vaccination decreased from 11.0 to 4.7 cases per 100,000 woman-years (above threshold), as compared to 2.8 cases (below threshold) under GN with 60% coverage and 2.4 cases (below threshold) under GN with 90% coverage. In conclusion, GN HPV vaccination is an effective strategy to improve the resilience to disruption of cancer prevention programmes and to enhance the progress towards cervical cancer elimination.

Quantification of impact of COVID-19 pandemic on cancer screening programmes – a case study from Argentina, Bangladesh, Colombia, Morocco, Sri Lanka, and Thailand

It is quite well documented that the COVID-19 pandemic disrupted cancer screening services in all countries, irrespective of their resources and healthcare settings. While quantitative estimates on reduction in volume of screening tests or diagnostic evaluation are readily available from the high-income countries, very little data are available from the low- and middle-income countries (LMICs). From the CanScreen5 global cancer screening data repository we identified six LMICs through purposive sampling based on the availability of cancer screening data at least for the years 2019 and 2020. These countries represented those in high human development index (HDI) categories (Argentina, Colombia, Sri Lanka, and Thailand) and medium HDI categories (Bangladesh and Morocco). No data were available from low HDI countries to perform similar analysis. The reduction in the volume of tests in 2020 compared to the previous year ranged from 14.1% in Bangladesh to 72.9% in Argentina (regional programme) for cervical screening, from 14.2% in Bangladesh to 49.4% in Morocco for breast cancer screening and 30.7% in Thailand for colorectal cancer screening. Number of colposcopies was reduced in 2020 compared to previous year by 88.9% in Argentina, 38.2% in Colombia, 27.4% in Bangladesh, and 52.2% in Morocco. The reduction in detection rates of CIN 2 or worse lesions ranged from 20.7% in Morocco to 45.4% in Argentina. Reduction of breast cancer detection by 19.1% was reported from Morocco. No association of the impact of pandemic could be seen with HDI categories. Quantifying the impact of service disruptions in screening and diagnostic tests will allow the programmes to strategize how to ramp up services to clear the backlogs in screening and more crucially in further evaluation of screen positives. The data can be used to estimate the impact on stage distribution and avoidable mortality from these common cancers.

Temporal trends in cervical cancer incidence and mortality in economically emerging countries, 1992–2021: an age-period-cohort analysis

Introduction The economically emerging countries contributed to over half of the global cervical cancer (CC) burden and are good examples showing how rapid economic growth and health policy change affect the trends of CC burden. This study aimed to analyse the time trends of CC burden across Brazil, Russia, India, China and South Africa (BRICS) and associations with age, period and birth cohort from 1992 to 2021. Methods Data on CC incident cases, deaths, age-standardised incidence rates (ASIRs) and age-standardised mortality rates (ASMRs) were sourced from the Global Burden of Disease Study 2021 to demonstrate the temporal trends of CC burden for BRICS countries from 1992 to 2021. An age-period-cohort model was used to determine the net drift, local drift, longitudinal age curves, as well as period and cohort relative risks regarding CC incidence and mortality. Results Between 1992 and 2021, the ASIR of CC decreased from 16.5 to 15.6 per 100 000 women (−5.5%) and the ASMR declined from 10.1 to 6.7 per 100 000 women (−33.7%) in BRICS. Brazil reported continuous decreases in both CC incidence (net drift: −1.1%, 95% CI −1.1% to −1.0%) and mortality (net drift: −1.7%, 95% CI −1.80% to −1.6%). India also had reduced CC incidence and mortality but experienced worsening period effects from 2012 onwards. Russia and China experienced decreasing trends in mortality yet increasing trends in incidence, and there were apparent unfavourable trends among young and middle-aged women in Russia. South Africa maintained the highest CC incidence (40.0 per 100 000 women, 95% CI 35.0 to 45.6) and mortality (21.3 per 100 000 women, 95% CI 18.8 to 24.1) across the BRICS and had the steepest growth of CC incidence and mortality rates with increasing age. Conclusion Despite an overall decreasing trend of CC burden in BRICS, substantial heterogeneity exists across nations. Identifying country-specific priority groups and tailoring interventions is essential, and the patterns observed have implications for public health strategies applicable not just to BRICS nations but also to many other emerging economies facing substantial CC burden.

Protocol for a cervical screening implementation trial comparing two approaches for delivering HPV self-collection in low-resource settings in India: a type 3 hybrid cluster randomised controlled trial (SHE-CAN)

Background Although multiple studies have offered self-collection for human papillomavirus (HPV)-based cervical screening in community settings, there are no randomised controlled trials (RCTs) that have compared implementation outcomes of programme approaches for self-collection. This trial will compare two such approaches in low-resource settings in the states of Tamil Nadu and Mizoram, India. Methods A cluster RCT will be conducted over a year, offering self-collection to 3000 women aged 30–49 from 28 clusters (average size 101) in selected districts. Clusters in tribal, rural and urban low-income settings will be randomised to two arms. The intervention arm, co-designed with multiple stakeholders, will involve campaigns to offer self-collection in the community. The comparison arm will be offered self-collection at the nearest health facilities. HPV-based cervical screening will be performed at central laboratories using clinically validated screening assays that can identify the highest risk carcinogenic HPV types (Group 1a–c - HPV16/18/31/33/45/52/58, ±35). Ablative treatment will be based on positivity with this extended genotyping triage, while those with any of the lower carcinogenic HPV types (Group 1d - 39, 51, 56, 59, ±35, Groups 2a/b - 66, 68) will undergo further assessment with visual inspection with acetic acid. Outcomes will be evaluated quantitatively and qualitatively using RE-AIM and the Theoretical Framework of Acceptability. Analysis The primary outcome will be percentage of women well-managed (screened and appropriately treated) in both arms, with secondary outcomes including proportion screened, proportion treated, acceptability (willingness to screen, rescreen, and/or recommend to others) to women, community and healthcare providers, adoption (by providers), implementation fidelity, costs, sustainability assessment and systematically identified implementation barriers and facilitators. The reach, effectiveness and acceptability of community-based self-collection and the use of extended genotyping for triage in resource-constrained, hard-to-reach populations will be assessed, with lessons that can inform future statewide and national programmes. Ethics and dissemination Ethics approval has been obtained from the Institutional Review Board (IRB) and Ethics Committee of the Christian Medical College Vellore, Tamil Nadu, India (IRB Min. No 14314; INTERVEN), the Alfred Hospital Ethics Committee (HREC Ref 80134, Local Reference: project 601/21), Melbourne, Australia, the IARC Ethics Committee (IEC 21-32), Lyon, France, the Salem Polyclinic Institutional Ethics Committee (SPCIEC/2022/June/01/02), Tamil Nadu, India and the Institutional Ethics Committee, Civil Hospital, Aizawl, Mizoram, India (No.B.12018/1/13-CHA(A)/IEC/115). The study is also approved by the State Scientific Advisory Committee, Directorate of Public Health and Preventive Medicine, Chennai, Tamil Nadu (R. No. 011575/HEB/A2/2023). The Alfred Hospital Approval, as an authorised Australian ethics committee for national mutual recognition, is recognised and registered with the University of Melbourne Human Research Ethics Committee (2024-25255-57650-1). Written informed consent will be obtained from participants. The results of the trial will be disseminated through a peer-reviewed medical journal, and also through workshops, reports and conferences. Trial registration number The trial has been registered with the Clinical Trials Registry - India: CTRI/2022/04/042327.

Readiness to transition to HPV self-collection from VIA screening: a mixed methods health systems assessment from Tamil Nadu, India

As a frontrunner in introducing cervical screening in India, the state of Tamil Nadu urgently needs to consider how to improve screening rates and switch to Human Papillomavirus (HPV) detection tests. We used a mixed methods design to assess the readiness of the state health system for delivering the current cervical screening program, as well as for future HPV self-collection. Following a desk review, we surveyed 14 government health facilities in three districts of Tamil Nadu and calculated overall and domain-specific (service utilization, service availability, general service, cervical screening) readiness scores as percentages. We conducted four interviews and five focus group discussions with 37 participants [managers, primary care nurses, community health workers (CHWs)] to clarify findings and obtain suggestions regarding the introduction of HPV self-collection in tribal, rural, and urban low-resource settings. Scores for general services and readiness to offer visual inspection with acetic acid (VIA) and follow-up were more than 70% in the surveyed facilities. Despite the availability of trained nurses, infrastructure and resources, utilisation was primarily limited to symptomatic women attending health facilities due to poor acceptability of screening that would require facility visits. Most participants felt that self-collection could reduce women's fear and embarrassment and could be delivered through CHWs in the community or by nurses at facilities. However, motivation for screening may remain low as most asymptomatic women do not perceive a need for screening, and/or fear implications of a positive test. Tertiary laboratories appear ready for HPV testing, given availability of high-throughput PCR equipment, computerised laboratory information management systems, and a planned hub and spoke model of improving access to laboratory tests. Despite relatively good infrastructure and staffing for VIA screening in public healthcare facilities, service utilisation was primarily by symptomatic women, contributing to low screening rates. HPV self-collection was highly acceptable to administrative and field staff. Widespread educational approaches to motivate asymptomatic women to screen using self-collection, with decentralised sample collection and treatment, could potentially improve cervical screening rates. Not applicable.

Barriers and attitudes toward cervical cancer screening among eligible women

This study examined barriers and attitudes toward cervical cancer screening among eligible women in São Paulo, Brazil, and their associations with sociodemographic factors, screening behaviors, and knowledge. A survey was conducted with 384 women aged 25-64 attending primary healthcare units, selected through multistage random sampling across 50 primary health units from 17 regional health departments of São Paulo. Participants rated barriers and attitudes using 5-point Likert items, which were later condensed in a 3-point scale for analysis. Non-parametric tests assessed associations with sociodemographic factors, screening practices, and knowledge levels. The sample was predominantly low-income (40% in the lowest income bracket; 82% without private health insurance), with 87% reporting a Pap smear within the past five years. Key personal and structural barriers included fear of bad news (41%), test results delays (30%), long wait times (30%), and shame (29%). Significant associations were found between lower income and reporting delays in test results (p = 0,020) and long wait times (p = 0,012), as well as between lower education and experiencing delays (p = 0,030) and shame (p = 0,007). Positive attitudes toward screening exceeded 95% overall and were stronger among women who understood the Pap smear's role in early detection (p = 0,026) and improving survival (p = 0,006). While screening participation was high, persistent socioeconomic disparities in access and personal barriers require targeted interventions. Strengthening primary healthcare systems with patient-centered approaches could improve screening adherence and reduce inequities.

A randomised controlled non-inferiority trial to compare the efficacy of ‘HPV screen, triage and treat’ with ‘HPV screen and treat’ approach for cervical cancer prevention among women living with HIV

We report results of a randomized controlled trial to compare 'HPV screen and treat' (Arm 1) and 'HPV screen, triage and treat' (Arm 2) in women living with HIV (WLHIV), using visual inspection with acetic acid (VIA) as the triaging test. Treatment was offered to all HPV-positive women in Arm 1 and to VIA-positive women in Arm 2 with either thermal ablation or large loop excision. All women underwent a repeat HPV test one year after randomization. The primary outcome was non-inferiority of HPV clearance of Arm 2 at one-year follow up when compared to Arm 1. Of 544 HPV-positive consenting WLHIV, 433 were randomised in a 1:1 ratio to trial arms. At baseline, CIN 2/3 lesions were detected in 16.7% and 13.3% women in Arm 1 and Arm 2 respectively. HPV clearance was observed in 56.6% (95%CI 48.9-64.1) women in Arm 1 and 41.4% (95%CI 34.3-48.7) women in Arm 2 at follow-up in the intention-to-treat population (P = 0.004). 'HPV screen, VIA triage and treat' strategy was non-inferior to the 'screen and treat' strategy as the lower bound of the 95% confidence interval from the regression model was greater than 0.49 in both intention-to-treat analysis (RR 0.73, 95%CI 0.59-0.91) and per-protocol analysis (RR 0.74, 95%CI 0.60-0.93) according to the pre-specified analysis plan. Clinical trial registration: CTRI/2020/02/023349.

Assessment of organization of cervical and breast cancer screening programmes in the Latin American and the Caribbean states: The CanScreen5 framework

AbstractBackgroundIn the Community of Latin American and Caribbean States (CELAC), breast cancer and cervical cancer are the first and third causes of cancer death among females. The objectives are to assess the characteristics of the cervical and breast cancer screening programmes in CELAC, their level of organization, and the association of screening organization and coverage of essential health services.MethodsRepresentatives of the Ministries of Health of 33 countries were invited to the CanScreen5 project. Twenty‐seven countries participated in a “Train The Trainers” programme on cancer screening, and 26 submitted data using standardized questionnaires. Data were discussed and validated.The level of organization of the screening programmes was examined adapting the list of essential elements of organized screening programmes identified in a recently published IARC study.ResultsTwenty‐one countries reported a screening programme for cervical cancer and 15 for breast cancer. For cervical cancer, 14 countries dedicated budget for screening (66.7%), and women had to pay in 3 countries for screening (14.3%), 9 for diagnosis (42.9%) and 8 for treatment (38.1%). Only 4 countries had a system to invite women individually (19.0%). For breast cancer, 8 countries dedicated budget for screening (53.3%), and women had to pay for screening in 3 countries (20.0%), diagnosis in 7 (46.7%) and treatment in 6 (40.0%). One country (6.7%) invited women individually.There was variability in the level of organization of both cancer screening programmes. The level of organization of cervical cancer screening and coverage of essential health services were correlated.ConclusionLarge gaps were identified in the organization of cervical and breast cancer screening services. CELAC governments need pragmatic public health policies and strengthened health systems. They should guarantee sustainable funding, and universal access to cancer diagnosis and treatment. Moreover, countries should enhance their health information system and ensure adequate monitoring and evaluation.

Faster Elimination of HPV Infection and Cervical Cancer Using Concomitant HPV Vaccination and HPV Screening: A Demonstration Project in Rwanda

Cervical cancer is the fourth most frequently diagnosed cancer and the fourth leading cause of cancer death in women, with an estimated 604,000 new cases and 342,000 deaths worldwide in 2020. Rwanda is among countries with a high burden cervical cancer, with an annual incidence of 28.2/100,000 women (1,229 new cases in 2020) and a mortality rate of 20.1/100,000 (829 deaths in 2018) according to WHO (IARC 2020). Cervical cancer is almost completely preventable because of the highly effective primary (HPV vaccine) and secondary (HPV screening) prevention measures. However, these measures have not been equitably implemented across and within LMICs countries. Given the current situation, where the screening coverage is still low due to financial and operational challenges, it will take many years to achieve the elimination targets as included in the global elimination strategy. We are proposing to implement an innovative strategy to accelerate the elimination of cervical cancer in Rwanda consisting of concomitant HPV vaccination and HPV screening for young women aged 23-29 years old. HPV screening and vaccination are complementary preventive options often implemented as separate public health programs. This project proposal aims to address this disconnect by combining both strategies with the ultimate purpose of accelerating the reduction of cervical cancer incidence and mortality in Rwanda and making the programs both cost-effective and sustainable. Primary objective The study aims to evaluate whether organized, concomitant HPV vaccination and HPV screening offered to girls and women aged 23-29 years will result in more rapid elimination of HPV infections in the target districts in Rwanda. The study design is a before-after study design of the intervention, where the projected incidences and prevalence at the 2-year follow-up visit are modeled using the data from the baseline visit, with evaluation using Observed/expected numbers. Secondary objectives The study will evaluate whether concomitant vaccination and cervical screening result in an improved efficiency and/or safety of the cervical cancer screening program. These objectives will be examined among women who participated in the combined screening and vaccination study. i) Protection of Gardasil 9 against HPV infection and against CIN2+ by Gardasil 9 HPV vaccine types in 23 to 29-year-old women from the study districts. This analysis will be performed every 2 years, and the first analysis will determine the effectiveness of one-dose vaccination (incident infections of HPV vaccine types at 2 years), whereas all subsequent analysis will determine the effect of 2-dose vaccinations. The study will be powered to detect a decline in invasive cervical cancer among the study participants, using the cervical cancer incidence in the surrounding districts of Rwanda as the reference. ii) Efficiency will also be measured by the yield of histopathologically confirmed high-grade cervical cancer precursors or cancer (cervical intraepithelial neoplasia grade 2, 3, or cervical cancer) in relation to the consumption of resources and convenience for the women, using the yield at the baseline visit (10% of women tested) as the comparator. The hypothesis is that 2 years after vaccination, there will be only a few incident infections (only some old, persistent infections) resulting in high PPV and high yield of CIN2+ at modest consumption of resources. End of the study One screening interval (2 years) after the last visit of the last subject, defined as the day the last study subject receives her second vaccination. The study will be implemented in 4 districts of Rwanda covering 100,000 women aged 23 to 29 years old. We will use Gardasil 9, the HPV the second generation HPV Vaccine manufactured by Merck.

Development, Field Testing and Evaluation of the Efficacy of a Hand-held, Portable and Affordable Thermo-coagulator to Prevent Cervical Cancer in Low- and Middle-income Countries

This project develops, tests and produces a lightweight, cordless, battery driven and rechargeable hand-held device for treating cervical precancer (Liger Thermal Coagulator). The study evaluates its effectiveness compared to the current standard treatment (cryocautery) when used as part of a screen and treat programme using Visual Inspection with Acetic acid (VIA) in Sub Saharan Africa.