QuestionWhat is the prevalence of human papillomavirus (HPV) and other sexually transmitted infections (STIs) with simultaneous testing of mailed self-collection kits in a population of low-income women?FindingsIn this secondary analysis of a randomized clinical trial including 327 intervention participants, nearly 1 in 6 participants tested positive for other STIs, the same rate as those positive for HPV.MeaningThese findings suggest that streamlining testing for both HPV and other STIs may address multiple preventive care needs among underscreened women. This secondary analysis of a randomized clinical trial evaluates whether self-testing for chlamydia, gonorrhea, and trichomoniasis at the same time as human papillomavirus improves uptake of testing among underscreened women. ImportanceHuman papillomavirus (HPV) self-collection increases cervical cancer screening uptake among women underscreened for cervical cancer, particularly those from marginalized low-income and racial and ethnic backgrounds. Underscreened women are also at high risk for other sexually transmitted infections (STIs) that can be similarly screened via self-collection.ObjectiveTo evaluate an intervention streamlining testing for other STIs alongside HPV self-collected samples among low-income women.Design, Setting, and ParticipantsThis is a secondary analysis of the My Body, My Test-3 study, a randomized clinical trial testing a mailed self-collection intervention to improve cervical cancer screening. The My Body, My Test-3 study was conducted from April 2016 to December 2019 in 22 counties in North Carolina among low-income women overdue for cervical cancer screening. This analysis included participants randomized to the trial intervention group with valid STI and HPV results. Data analysis occurred from October 2024 to February 2025.InterventionThe intervention included a mailed self-collection kit and instructions to self-collect a cervicovaginal sample. Samples were tested for other STIs and HPV using the Aptima assay.Main Outcomes and MeasuresThe primary outcome was a positive test result for other STIs (including chlamydia, gonorrhea, and trichomoniasis). A risk factor analysis was conducted to identify factors associated with testing positive for other STIs. Secondary outcomes included rate of follow-up care and perceptions of self-collection among participants with positive STI results.ResultsAmong 327 participants (median [IQR] age, 42 [25-63] years; 38 [8.6%] Hispanic, 146 [44.7%] non-Hispanic Black, and 133 [40.7%] non-Hispanic White), 51 (15.6%) tested positive for other STIs and 51 (15.6%) tested positive for HPV; 7 (2.1%) tested positive for both. Risk factors for other STIs included non-Hispanic Black race and ethnicity compared with non-Hispanic White race and ethnicity (adjusted odds ratio [aOR], 4.1; 95% CI, 1.5-11.6), having 2 or more sexual partners in the last year compared with having none (aOR, 5.7; 95% CI, 1.0-31.4), single marital status compared with married or partnered status (aOR, 5.6; 95% CI, 1.1-27.9), and current smoking compared with none (aOR, 4.1; 95% CI, 1.7-10.4). Among participants who tested positive for other STIs, 34 (66.7%) received follow-up care. Most participants (130 [84.4%]) preferred testing for both HPV and other STIs in the future.Conclusions and RelevanceIn this secondary analysis of a randomized clinical trial of 327 participants, nearly 1 in 6 tested positive for other STIs via streamlined testing in a mailed HPV self-collection intervention. Self-collection may improve both cervical cancer and STI screening for women from marginalized backgrounds.Trial RegistrationClinicalTrials.gov Identifier: NCT02651883

Background: Persistent high-risk human papillomavirus (hrHPV) infection can lead to cervical precancer, with women living with HIV (WLWH) at increased risk due to impaired immune clearance. Thermal ablation (TA) is a low-cost treatment for precancerous lesions, but data on hrHPV persistence after TA among WLWH are limited. Objectives: To evaluate overall and channel-specific hrHPV persistence 12 months after TA among women in Lilongwe, Malawi. Design: Cross-sectional analysis of Malawian women who received TA during and after the PEER trial (prevention of cervical cancer through two HPV-based screen-and-treat implementation models in Malawi). Methods: We analyzed 495 hrHPV-positive women (113 WLWH, 382 without HIV) treated with TA. Self-collected cervicovaginal samples were obtained before treatment and at 12 months post-treatment and tested with the GeneXpert HPV assay, which detects hrHPV across five high-risk genotype channels (P1–P5). Channels P3–P5 were grouped as non-16/18/45 hrHPV types (HPV 31, 33, 35, 39, 51, 52, 56, 58, 59, 66, 68). Persistence was defined as the detection of the same channel at both time points. Differences in persistence rates were assessed using Fisher’s exact and Welch’s t -tests. Results: At 12 months post-TA, 35.6% of women were persistently hrHPV-positive. Persistence was higher among WLWH (46.0%) than women without HIV (32.0%, p = 0.01). By genotype, persistence was most common for non-16/18/45 types (37.7%), followed by HPV16 (28.9%) and HPV18/45 (18.0%). WLWH had higher persistence of non-16/18/45 types (51.8% versus 33.7% in HIV-negatives, p = 0.003), while persistence of HPV16 (35.0% versus 27.1%, p = 0.58) and HPV18/45 (26.3% versus 14.9%, p = 0.14) did not differ significantly. Conclusions: Over one-third of women had persistent hrHPV 12 months after TA, with higher rates among WLWH, primarily for non-16/18/45 genotypes. Findings highlight the need for enhanced follow-up and adjunct therapies to improve post-treatment clearance and advance cervical cancer prevention in low-resource settings.

BackgroundCervical cancer is a leading cause of death among women in Africa, yet Human papillomavirus (HPV) vaccination and self-collection screening remain underutilized. HPV vaccination significantly reduces cervical cancer risk; additionally, HPV self-collection can improve screening access to prevent progression to invasive cervical cancer. Few studies use theory-driven approaches to examine contextual factors influencing cervical cancer prevention. Guided by the PEN-3 Cultural Model, this qualitative study examined social and cultural influences, facilitators, and preferences related to HPV vaccination and HPV self-collection among Nigerian girls and women.MethodsSemi-structured, in-depth interviews with girls (9–26 years) and women (30–65 years) in Lagos, Nigeria, explored perceptions and preferences related to cervical cancer prevention. Using the PEN-3 cultural model, thematic analysis examined how Cultural Identity, Relationships and Expectations, and Cultural Empowerment domains influenced participants' preferences and behaviors. Multilevel factors such as knowledge gaps, misconceptions, high costs, and limited access were categorized, and positive and negative influences on HPV prevention behaviors were identified.ResultsA total of 56 purposively selected participants (girls aged 9–26 years and women aged 30–65 years) were included in the study. For HPV vaccination, girls reported that recommendations from the health ministry (n = 24, 86%), health providers (n = 24, 86%), and family and friends (n = 18, 64%) strongly influenced their decisions. For HPV self-collection, adult women prioritized messages from health providers (n = 27, 96%) and health ministry officials (n = 25, 89%). Findings demonstrated that multilevel (i.e., individual, relational, sociocultural, and structural) factors influence HPV vaccination and HPV self-collection. Across both groups, limited knowledge, concerns about cost and access, and misconceptions about cervical cancer, some cultural beliefs, including stigma, were identified as barriers to prevention behaviors. For younger participants, family dynamics significantly influenced decision-making. Among older women, concerns related to privacy, trust in healthcare providers, spousal support, and preferences for female providers were described as key drivers for HPV self-collection. Participants expressed a strong preference for affordable, accessible vaccines and self-collection kits available at health facilities and pharmacies.ConclusionCulturally grounded cervical cancer prevention strategies that align with women's preferences and leverage existing community resources are essential for empowering informed decision-making and increasing HPV vaccination and self-collection.

Importance:Anal cancer screening is recommended for high-risk populations, particularly sexual and gender minority (SGM) individuals. However, the cost-effectiveness of home-based self-sampling in increasing anal cancer screening uptake has not yet been evaluated in the US. Objective:To evaluate the cost-effectiveness of home-based anal self-sampling compared with clinic-based screening among SGM individuals. Design, Setting, and Participants:This economic evaluation used data from a 2-group randomized clinical trial conducted in Milwaukee, Wisconsin, from January 2020 to August 2022, enrolling SGM individuals aged 25 years or older. Participants were randomized to home-based self-sampling or clinic-based screening. Costs for home-based screening were obtained from the trial, and clinic-based costs were sourced from the Medicare reimbursement schedule. Travel and time costs were derived on the basis of participant self-reports. The analysis was performed between February and October 2025. Intervention:Participants in the home-based screening group received self-sampling supplies and instructions, and those in the clinic-based screening group were instructed to visit a clinic for anal cancer screening. Main Outcomes and Measures:The primary outcome was the incremental cost-effectiveness ratio (ICER), measured as the additional cost needed to increase screening participation by one person. The 95% CIs for the ICERs were estimated using a bootstrap method with 1000 iterations. Net benefit regression and cost-effectiveness acceptability curves were used to assess the likelihood of cost-effectiveness across different willingness-to-pay (WTP) thresholds. Results:The study included 240 SGM individuals (227 with gender identity as a man [95%]; median [IQR] age, 46 [33 to 57] years), of whom 65 (27%) had HIV. The cost per participant was $64.18 for home-based screening and $60.40 for clinic-based screening from a societal perspective, and $61.91 for home-based screening and $42.06 for clinic-based screening from a health care payer perspective. Home-based screening was associated with increased screening participation vs clinic-based screening (107 participants [89.2%] vs 89 participants [74.2%]). The ICER per additional screened participant was $25.19 (95% CI, -$27.66 to $104.60) for the societal perspective and $132.36 (95% CI, $74.54 to $402.20) for the health care payer perspective. Home-based screening had a 49.6% probability of being cost-effective at a WTP of $25, 99.99% at a WTP of $100 (societal perspective), and 90.9% at a WTP of $200 (health care payer perspective). The ICERs for home-based screening compared with clinic-based screening were highly sensitive to screening participation rates. Conclusions and Relevance:The findings of this economic analysis suggest that home-based anal cancer screening is a cost-effective approach to increasing screening participation among SGM individuals. Home-based screening may serve as a valuable and efficient tool for expanding screening rates.

BACKGROUND:Perceived financial barriers to cervical cancer screening in the United States are well documented. However, few data compare perceived cost barriers with actual screening costs. Our objective was to compare individuals' expected screening costs with actual screening costs. Additionally, we explore cost differences for Black and White participants to better understand how perceived financial barriers may contribute to screening disparities. METHODS:We utilized control arm (n = 227) data from the MBMT-3 trial of low-income underscreened women in North Carolina. At baseline, participants were asked their expected screening and screening-associated costs (i.e., lost wages, transportation, child/dependent care, etc.). After in-clinic screening, participants reported their actual costs. We calculated differences between individuals' expected versus actual costs, overall and for Black and White participants. We examined sociodemographic predictors of expected costs and expected-actual cost difference. RESULTS:Participants expected screening to cost a median $200 (IQR: 100-300), primarily for appointments and laboratory tests. Black participants expected higher screening costs (median $265) than White participants ($205). Participants who completed screening overestimated expenses, with median expected costs of $215 compared with $5 for actual costs. Participants overestimated costs for every category: appointment and laboratory tests, lost wages, transportation, and child/dependent care. Actual costs were similar for Black and White participants. CONCLUSION:Educational outreach about existing affordable screening services may reduce perceived financial barriers, particularly for historically marginalized populations. IMPACT:Among an underscreened population perceiving high financial barriers, participants overestimated screening costs, with Black participants expecting higher costs than White participants. High expected costs indicate low awareness of subsidized screening options. See related In the Spotlight, p. 1061.

Importance:Human papillomavirus (HPV) self-collection increases cervical cancer screening uptake among women underscreened for cervical cancer, particularly those from marginalized low-income and racial and ethnic backgrounds. Underscreened women are also at high risk for other sexually transmitted infections (STIs) that can be similarly screened via self-collection. Objective:To evaluate an intervention streamlining testing for other STIs alongside HPV self-collected samples among low-income women. Design, Setting, and Participants:This is a secondary analysis of the My Body, My Test-3 study, a randomized clinical trial testing a mailed self-collection intervention to improve cervical cancer screening. The My Body, My Test-3 study was conducted from April 2016 to December 2019 in 22 counties in North Carolina among low-income women overdue for cervical cancer screening. This analysis included participants randomized to the trial intervention group with valid STI and HPV results. Data analysis occurred from October 2024 to February 2025. Intervention:The intervention included a mailed self-collection kit and instructions to self-collect a cervicovaginal sample. Samples were tested for other STIs and HPV using the Aptima assay. Main Outcomes and Measures:The primary outcome was a positive test result for other STIs (including chlamydia, gonorrhea, and trichomoniasis). A risk factor analysis was conducted to identify factors associated with testing positive for other STIs. Secondary outcomes included rate of follow-up care and perceptions of self-collection among participants with positive STI results. Results:Among 327 participants (median [IQR] age, 42 [25-63] years; 38 [8.6%] Hispanic, 146 [44.7%] non-Hispanic Black, and 133 [40.7%] non-Hispanic White), 51 (15.6%) tested positive for other STIs and 51 (15.6%) tested positive for HPV; 7 (2.1%) tested positive for both. Risk factors for other STIs included non-Hispanic Black race and ethnicity compared with non-Hispanic White race and ethnicity (adjusted odds ratio [aOR], 4.1; 95% CI, 1.5-11.6), having 2 or more sexual partners in the last year compared with having none (aOR, 5.7; 95% CI, 1.0-31.4), single marital status compared with married or partnered status (aOR, 5.6; 95% CI, 1.1-27.9), and current smoking compared with none (aOR, 4.1; 95% CI, 1.7-10.4). Among participants who tested positive for other STIs, 34 (66.7%) received follow-up care. Most participants (130 [84.4%]) preferred testing for both HPV and other STIs in the future. Conclusions and Relevance:In this secondary analysis of a randomized clinical trial of 327 participants, nearly 1 in 6 tested positive for other STIs via streamlined testing in a mailed HPV self-collection intervention. Self-collection may improve both cervical cancer and STI screening for women from marginalized backgrounds. Trial Registration:ClinicalTrials.gov Identifier: NCT02651883.

BackgroundCervical cancer is a leading cause of cancer deaths among women in Nigeria, yet awareness is low. Historically, art has served as a medium for processing emotions and sharing experiences, which can be effective in promoting health and behavior change. ObjectiveThis study aimed to examine art submissions and social media engagement from a Nigerian crowdsourcing open call to inform co-designed strategies for cervical cancer prevention among women. MethodsThis study reported following the SRQR (Standard Reporting for Qualitative Research) guideline. From October to November 2023, we launched an open call for art on social media, inviting adult women to submit artwork that raises awareness about cervical cancer prevention. Participants’ submissions were anonymized and reviewed by an independent panel of judges. A total of 6 finalists were selected to participate in a social media contest during Cervical Cancer Elimination Week, and 3 winners were identified based on total social media likes and comments, as well as grading rubric scores. We analyzed participants’ art entries through thematic analysis in six steps: (1) familiarization, (2) creating categories, (3) identifying themes, (4) reviewing themes, (5) defining themes, and (6) discussing findings. The emerging themes included using art to express emotions, to convey health-related content, and to use art as a form of self-regulation, which were further analyzed using the Relationships and Expectations domain of the PEN-3 (perceptions, enablers, and nurturers) cultural model. ResultsA total of 43 entries from participants aged 18-27 (mean 22.2, SD 2.6) years were analyzed. The entries included visuals (n=14), audiovisual (n=14), text (n=14), and audio (n=1). Most entries (42/43, 97.6%) focused on cervical cancer and human papillomavirus, covering definitions, risk factors, treatment, and prevention. Using the PEN-3 cultural model’s Relationships and Expectations domain for analysis, 62.8% (27/43) addressed “perceptions” of art as a means of mental and emotional expression, reflecting feelings such as humor, sadness, hope, faith, unity, and fear related to cervical cancer prevention. A majority (34/43, 79.1%) aimed to promote human papillomavirus screening and vaccination and were categorized as “enablers,” viewing art as a tool for health awareness, including educational resources. Additionally, 7% (3/43) included “nurturers,” representing self-regulation addressing stresses linked to having relatives with cervical cancer. Six finalist entries were shared on social media to promote cervical cancer awareness, reaching 8685 individual Instagram accounts and generating 2727 likes and 782 comments. ConclusionsThis study used art to increase awareness about cervical cancer on social media. Art can serve as a tool for promoting health by incorporating visual, emotional, and contextual messages to influence the target audience’s behavior.

CpG site methylation patterns have potential to improve differentiation of high-grade screening-detected cervical abnormalities. We assessed CpG differential methylation (DM) and differential variability (DV) in high-grade (CIN2+) vs low-grade (≤ CIN1) lesions. In ≤ CIN1 (n = 117) and CIN2+ (n = 31) samples, cervical sample DNA underwent testing with Illumina HumanMethylation arrays. We assessed DM and DV of CpG methylation M-values among 9 cervical cancer-associated genes. We fit CpG-specific linear models and estimated empirical Bayes standard errors and false discovery rates (FDRs). An exploratory epigenome-wide association study (EWAS) aimed to detect novel DM and DV CpGs (FDR < 0.05) and Gene Ontology (GO) term enrichment. Compared to ≤ CIN1, CIN2+ exhibited greater methylation at CCNA1 cluster 1 (M-value difference 0.24; 95% CI, 0.04-0.43) and RARB cluster 2 (0.16; 95% CI, 0.05-0.28), and lower methylation at CDH1 cluster 1 (-0.15; 95% CI, -0.26 to -0.04). CIN2+ exhibited lower variability at CDH1 cluster 2 (variation difference -0.24; 95% CI, -0.41 to -0.05) and FHIT cluster 1 (-0.30; 95% CI, -0.50 to -0.09). EWAS detected 3534 DM and 270 DV CpGs. Forty-four GO terms were enriched with DM CpGs related to transcriptional, structural, developmental, and neuronal processes. Methylation patterns may help triage screening-detected cervical abnormalities and inform US screening algorithms. This article is part of a Special Collection on Gynecological Cancer.

BACKGROUND:Evidence of self-collection human papillomavirus (HPV)-RNA testing in cervical cancer screening is limited among women with HIV (WHIV). Most studies are in low-risk patient populations in high-income countries. We examine the prevalence of high-risk HPV (hrHPV) using the APTIMA HPV-RNA assay on self-collected versus provider-collected specimens, and the associated risk factors for high-grade cervical intraepithelial neoplasia (CIN2/3) among women engaged in sex work in Kenya. Among WHIV, we examine the performance of both collection methods for the detection of CIN2/3. METHODS:Participants were aged ≥18 years, non-pregnant and had no previous treatment for cervical precancer. The screening process included self-collection of cervicovaginal samples using a Viba cytobrush (Rovers), provider-collected cervical samples, visual inspection with acetic acid (VIA) and Pap smear. The APTIMA HPV Assay (Hologic) was used to detect E6/E7 oncogene RNA of 14 hrHPV types in both self-collected and on provider-collected samples. Risk factors for CIN2/3 were determined via multivariable logistic regression. We estimated test characteristics for each screening method for CIN2/3 detection. RESULTS:A total of 400 women (194 WHIV, 206 women without HIV) underwent screening between 2013 and 2018, with 399 valid HPV results. WHIV had a higher prevalence of hrHPV by self-collection compared with women without HIV (44.0% vs 29.6%, p<0.05) and CIN2/3 (19.0% vs 9.7%, p<0.05). After adjusting for age and HIV status, hrHPV-positivity increased the risk of CIN2/3 by 13 to 20 times. Among WHIV, the sensitivity for CIN2/3 detection was similar between self-collection (85% (66-96)) and provider-collection (93% (76-99)), both of which were higher than the sensitivity of high-grade cytology (high-grade squamous intraepithelial lesion cut-off) (47% (95% CI 23 to 72)). The specificity for both collection methods (self: 66% (95% CI 57 to 75) and provider: 67% (95% CI 58 to 75)) was lower than cytology (85% (95% CI 78 to 91)). CONCLUSION:Self-collection for HPV-RNA testing performed similarly to provider-collection among WHIV. For WHIV, while the higher sensitivity of HPV-RNA testing compared with cytology for the detection of clinically relevant cervical disease is important, the lower specificity supports the inclusion of a triage test in the screening algorithm.

BACKGROUND:Invasive Cervical cancer is a largely preventable disease through screening, but access to cervical cancer screening (CCS) remains a challenge in Malawi. Integration of CCS with family planning (FP) services through Human papillomavirus (HPV) self-sampling may increase screening coverage. We aimed to evaluate women's perceptions, motivations, and satisfaction with integration of HPV self-sampling with family planning in Malawi. METHODS:In this mixed-methods study, we purposively sampled and interviewed 29 women who underwent HPV self-sampling for CCS through one of two different CCS-FP integration models in Malawi. We also completed 766 Client Exit Surveys with CCS patients from both models. Model 1 involved only clinic-based HPV self-sampling, while Model 2 included both clinic-based and community-based HPV self-sampling supported by community health workers. In-depth interviews (IDIs) were conducted using a semi-structured guide, audio-recorded, transcribed, and translated into English for analysis. Qualitative data were analyzed using NVivo 12.0 software and thematic analysis, and quantitative data were analyzed using statistical software. RESULTS:Women screened in both models reported reduced transport costs for screening. Those clinic-based valued the convenience of accessing both CCS and FP services in a single visit while those screened in the community appreciated accessing services within their communities. Many found HPV self-sampling easy to use and ensured privacy, especially in the community model where samples were mainly collected within their homes, rather than public toilets or clinic consultation rooms. Women were motivated to undergo CCS due to the perceived risks of cervical cancer, particularly among those living with HIV, the availability of services within the community, and the experience of gynecological symptoms. IDI women expressed satisfaction with being able to make decisions without consulting their spouses, and none reported experiencing social harm following the disclosure of HPV results. The client exit survey data showed that 92.5% of women in both models were very satisfied with the procedure. CONCLUSION:Our findings highlight that women were satisfied with HPV self-sampling, valuing its convenience, privacy, and cost-effectiveness, which enhanced their willingness to undergo CCS. These findings suggest that integrating CCS self-sampling into FP services could potentially improve CCS uptake in Malawi.

Background: Primary testing for high-risk human papillomavirus (HPV) via self-collection can increase cervical cancer screening rates. In the United States, federally qualified health center (FQHC) patients often have low incomes, lack health insurance, are medically underserved, and are screened less than the national average. Implementation of HPV self-collection can increase cervical cancer screenings among FQHCs. Objectives: To assess the potential impact of implementing HPV self-collection with FQHC patients by considering perspectives of frontline clinical and administrative staff and leadership to identify patient-focused implementation considerations. Design: This qualitative study utilized focus groups and key informant interviews, and transcripts were analyzed using a coding-based thematic analysis. Emergent themes regarding self-collection implementation perspectives were mapped onto Consolidated Framework for Implementation Research constructs to identify potential facilitators and barriers to implementation for FQHC patient populations. Methods: Participants from six FQHCs in North Carolina were identified. Forty-five clinical and administrative staff participated in focus groups. One chief executive officer, senior level administrator, chief medical officer, and clinical data manager from each FQHC ( N = 24) were interviewed one-on-one. Coding-based thematic analysis was applied to focus group and interview transcripts to uncover emerging themes. Results: Interviewees indicated that HPV self-collection can be advantageous to patients who do not routinely visit the clinic due to socioeconomic and cultural barriers. Programs must consider these barriers and patient literacy to ensure proper self-collection utilization. For example, FQHC patients may benefit from illustrated instructions for proper self-collection procedures. Conclusion: Tailoring an HPV self-collection implementation to FQHC patient populations may be an important strategy for increasing screening.

Supplementary Table from Extended Human Papillomavirus Genotyping to Predict Progression to High-Grade Cervical Precancer: A Prospective Cohort Study in the Southeastern United States

Introduction Cervical cancer disproportionately affects women in low- and middle-income countries (LMICs), who account for 90% of deaths from the disease. Human papillomavirus (HPV) is responsible for 99% of cervical cancer cases. Women living with HIV (WLWH) have a higher risk of persistent HPV infection and a greater likelihood of developing cervical cancer. Prevention of cervical cancer requires effective screening and precancer treatment programs. In LMICs, the common treatment method for cervical precancer is thermal ablation. However, for WLWH, thermal ablation is associated with high rates of persistent HPV infection following treatment, a key risk factor for precancer recurrence. Adjuvant topical treatments with cytotoxic or antiviral properties may reduce HPV persistence following ablation. Preclinical and early-phase clinical trials indicate that topical artesunate is active against HPV-associated anogenital lesions, including cervical precancer, and can induce HPV clearance. Consequently, intravaginal artesunate may improve HPV clearance following thermal ablation, although no clinical trials have investigated this. Methods We are conducting a phase II, double-blind, randomized, placebo-controlled trial among 120 HIV seropositive women in Kenya to investigate the feasibility of self-administered intravaginal artesunate pessaries as adjuvant therapy following thermal ablation treatment for cervical precancer. The primary outcome is type-specific HPV clearance 6 months after randomization. Secondary outcomes are safety, adherence, acceptability, uptake, and retention. Participants will be enrolled at least 4 weeks after ablation and will self-administer pessaries on weeks 1, 3, and 5, with alternating drug-free weeks. Study follow-up will extend to 24 weeks after randomization. Conclusion High rates of persistent HPV infection in WLWH is a key limitation of thermal ablation, the most accessible cervical precancer treatment in LMICs. This trial will investigate the feasibility of repurposing topical artesunate as an adjuvant therapy to improve HPV clearance following thermal ablation in WLWH. Trial Registration ClinicalTrials.gov identifier: NCT06519994

BACKGROUND:In randomised controlled trials in Kenya and Uganda, a dynamic choice HIV prevention (DCP) intervention that offered structured choice of biomedical prevention product and opportunity to change products over time substantially improved prevention coverage; incident HIV infections were eliminated when long-acting cabotegravir was included as an option. We aimed to assess the potential cost-effectiveness of the intervention regimen in east, central, southern, and west Africa. METHODS:We used the existing individual-based HIV Synthesis model. Through sampling of parameter values at the start of each model run of a simulated population of adults, we created 1000 setting-scenarios, reflecting uncertainty in assumptions and a range of characteristics similar to those seen in east, central, southern, and west Africa. For each setting-scenario, we simulated predicted outcomes including disability-adjusted life-years (DALYs) and costs up to 50 years resulting from (1) continuing with the status quo (ie, no DCP); (2) introduction of the DCP intervention with oral pre-exposure prophylaxis (PrEP), post-exposure prophylaxis (PEP), and condoms without long-acting cabotegravir PrEP (ie, DCP without cabotegravir); and (3) introduction of the DCP intervention and including long-acting cabotegravir PrEP (ie, DCP including cabotegravir). We used a cost-effectiveness threshold of US$500 per DALY averted, and a discount rate of 3% per year. The annual cost of DCP including cabotegravir was assumed to be $190 per person. Net DALYs averted was calculated by DALYs averted plus the difference in costs divided by the cost-effectiveness threshold. FINDINGS:Reflecting the trial results, among people with a PrEP indication (ie, having an HIV acquisition risk) and an HIV test in the past 3 months, the median proportion of people on PrEP was 14% (90% range 4-43) with no DCP, 54% (23-74) with DCP without cabotegravir, and 71% (35-83) with DCP including cabotegravir. These increases in PrEP use led to HIV incidence reductions, with incidence rate ratios of 0·89 (0·67-1·17) for DCP without cabotegravir and 0·64 (0·44-0·97) for DCP including cabotegravir, relative to no DCP. Across setting-scenarios, both DCP policies led to DALYs being averted: 18 400 DALYs per year (95% CI 16 700-20 100) for DCP including cabotegravir and 56 400 DALYs per year (52 300-60 500) for DCP without cabotegravir in 10 million adults. Compared with no DCP, there was a mean increase in annual discounted costs over 50 years: $8·6 million (7·7-9·4) for DCP without cabotegravir and $13·2 million (11·6-14·8) for DCP including cabotegravir. Addition of long-acting cabotegravir PrEP to DCP was cost-effective (vs DCP without cabotegravir); the incremental cost-effectiveness ratio for DCP including cabotegravir (vs no DCP) was $234 per DALY averted. There was substantial variation across setting-scenarios and we found that DCP was more likely to be the cost-effective choice in settings with high prevalence of unsuppressed HIV or low proportion of people with an indication for PrEP. INTERPRETATION:Offering structured PrEP and PEP choice including long-acting cabotegravir and enabling risk-informed use could reduce HIV incidence by a third over 10 years. If projected generic production costs of long-acting cabotegravir can be realised, it is likely to be cost-effective across multiple settings in east, central, southern, and west Africa. FUNDING:US National Institutes of Health.

Background:Catch-up HPV vaccination is challenging in many low and middle-income countries (LMICs). Pay-it-forward offers an individual a subsidized vaccine, then an opportunity to donate to help others access vaccinations. Our randomized control trial assessed the effectiveness of pay-it-forward in improving HPV vaccination among girls aged 15-18 years in China. Methods and findings:Eligible participants were randomly assigned to either the pay-it-forward arm or standard-of-care arm (self-paid vaccination). The primary outcome was the first-dose HPV vaccination rate, verified against clinical records. Among 321 participants enrolled, most caregivers were female (80.1%). In the pay-it-forward arm, 55 of 161 (34.2%) girls received the HPV vaccine, compared with 28 of 160 (17.5%) girls in the standard-of-care arm (adjusted proportion difference = 17.9%, 95% CI: 8.7, 27.0, P<0.001). Among 55 girls in the pay-it-forward arm who received the vaccination, 37 (67.3%) wrote a postcard message, and 39 (70.9%) of their caregivers donated to support future girls. The financial cost per person vaccinated was $294 in the standard-of-care arm and $230 in the pay-it-forward arm. Conclusions:The pro-social pay-it-forward strategy was effective to increase catch-up HPV vaccination among teenage girls with comparable costs. Trial registration:ChiCTR2200055542.

Background: Mailed self-collection kits for high-risk human papillomavirus (HPV) detection can increase access to cervical cancer screening among underscreened women. To design effective screening programs, it is necessary to evaluate women's understanding, reactions, and preferences for self-collected HPV test result delivery. Methods: The My Body, My Test-3 trial assessed the effectiveness of mailed HPV self-collection kit outreach. Between 2016 and 2019, the trial enrolled low-income women aged 25 to 64 years in North Carolina overdue for cervical cancer screening. Our analytical sample included women from the intervention arm who conducted at-home self-collection, returned a self-collection kit, had a conclusive HPV result, and completed a follow-up survey after results were received by phone but before in-clinic screening. We evaluated women's understanding, reactions, and preferences for result delivery, stratified by result positivity. Results: Among 296 diverse, low-income women, 16% (n = 47/296) had an HPV-positive result and 84% (n = 249/296) had an HPV-negative result. Most women understood their results as an indicator of cervical cancer risk, and 93% (n = 264/284 who responded) correctly recalled their results 1 week post-receipt. Women with a positive result more frequently reported feeling afraid and worried, and less frequently reported feeling relieved, compared with those with a negative result (all P < 0.001). Most women were comfortable receiving results by phone (HPV-positive result: 85%, n = 40/47; HPV-negative result: 96%, n = 238/249), although some with a positive result had remaining questions. Conclusions: Although most women delivered their mailed, self-collected HPV result by phone understood their result, future US screening programs should provide educational support during and after HPV-positive result delivery.

Randomized Controlled Trials Included to Populate In-Clinic Screening Uptake Estimates for Usual Care Alternative

Previous studies showed the association between sexually transmitted infections (STIs) and cervical lesions remains ambiguous. This study was conducted among 8371 women from a screening cohort. Seven specific sexually transmitted pathogens (STPs), including one viral [high-risk human papillomavirus (hrHPV), low-risk HPV (lrHPV)], five bacterial [Ureaplasma parvum (UP), Mycoplasma hominis (MH), Ureaplasma urealyticum (UU), Chlamydia trachomatis (CT), and Mycoplasma genitalium (MG)], and one parasitic [Trichomonas vaginalis (TV)] pathogen, were tested by Next Generation Sequencing assay using well-stored baseline samples. Odds ratios (ORs) for incident cervical lesions with different STPs were calculated by Logistic Regression analysis. Within 3-year follow-up, 133 and 72 participants were diagnosed with histopathological cervical intraepithelial neoplasia grade 1 (CIN1) and CIN2+, respectively. The adjusted ORs (aORs) of atypical squamous cells of undetermined significance or worse (ASC-US+) for women with hrHPV, lrHPV, UP, MH, TV, CT, and MG infections were 2.62 (95% CI: 2.19-3.13), 1.94 (95% CI: 1.55-2.43), 1.48 (95% CI: 1.26-1.74), 1.47 (95% CI: 1.25-1.73), 1.65 (95% CI: 1.27-2.15), 1.26 (95% CI: 0.79-2.01) and 2.33 (95% CI: 1.41-3.85), respectively. The aORs of cytological high-grade squamous intraepithelial lesions (HSIL) for women with hrHPV, TV, and MG infections were 13.01 (95% CI: 5.78-29.31), 3.48 (95% CI: 1.38-8.75), and 5.87 (95% CI: 1.58-21.77). The aORs of CIN1 for hrHPV, lrHPV, and MH were 6.88(95% CI: 4.79-9.90), 2.04(95% CI: 1.29-3.14), and 1.47(95% CI: 1.02-2.11). The aOR of CIN2+ for women with hrHPV infection was 17.56 (95% CI: 10.31-29.92), no significance was observed for CIN2+ with non-hrHPV STIs. Specific STP infections were significantly associated with subsequent cervical cytological ASC-US+ (hrHPV, lrHPV, UP, MH, TV, and MG) and HSIL (hrHPV, TV, and MG). Infection with lrHPV and MH could increase the CIN1 risk in future though no obvious CIN2+ risk elevation was observed.

BACKGROUND:The USA has traditionally been the largest donor to health programmes in low-income and middle-income countries (LMICs). In January 2025, almost all such funding was stopped and prospects for its resumption are uncertain. The suddenness of the funding cuts makes it difficult for national health programmes in LMICs to adapt. We aimed to estimate the impact of these cuts on deaths and other outcomes (new infections, number of family planning users, and unplanned pregnancies) for four health areas that have been a focus of a substantial amount of US foreign assistance: HIV, tuberculosis, family planning, and maternal and child health. METHODS:We applied established mathematical models to the countries receiving US foreign assistance in each domain to estimate health impacts over the period 2025 to 2030. We used six models of HIV, three different approaches to estimate family planning impact, and one model each for tuberculosis and maternal and child health, applying these models to as many as 80 countries. We compared model projections assuming constant funding (status quo) with projections assuming complete elimination of US funding in each country. Some models also considered partial cuts or restoration of funding over time. FINDINGS:A complete cessation of US funding without replacement by other sources would lead to drastic increases in deaths from 2025 to 2030: 4·1 million (range 1·6-6·6) additional AIDS-related deaths across 55 countries, 606 900 (95% uncertainty interval [UI] 466 000-768 800) additional tuberculosis deaths across 79 countries, 40-55 million additional unplanned pregnancies and 12-16 million unsafe abortions across 51 countries, and 2·5 million (1·3-4·5) additional child deaths from causes other than HIV and tuberculosis across 24 countries. Restoration of funding for HIV treatment but not prevention would avoid most of the increase in deaths but still result in nearly 1 million more new HIV infections from 2025 to 2030. INTERPRETATION:Substantial progress has been made in improving global health in the past few decades. This progress has strengthened hope in reaching global development goals. However, the recent funding cuts threaten to change these trajectories and could lead to sharp increases in avoidable mortality for the poorest countries. Even a partial restoration of US funding would combat the most severe effects and provide time for countries that have received substantial US foreign assistance to adjust to the new funding landscape. FUNDING:Economic and Social Research Council; Engineering and Physical Sciences Research Council; European and Developing Countries Clinical Trials Partnership; Gates Foundation; Global Fund to Fight AIDS, Tuberculosis, and Malaria; Open Philanthropy; UK Foreign, Commonwealth & Development Office; UK Medical Research Council; UN Population Fund; UNAIDS; US National Institute of Allergy and Infectious Diseases; University of Edinburgh; US National Institutes of Health; US President's Emergency Plan for AIDS Relief; Wellcome Trust; World Bank; WHO.