Women living with HIV (WLHIV) face a higher risk of developing cervical cancer. India carries a significant burden of HIV, with an estimated 2.5 million people living with HIV in 2023. While the introduction of more effective antiretroviral therapy has improved the life expectancy of WLHIV, it has also extended the risk window for persistent human papillomavirus (HPV) infection and cervical disease progression. Cervical cancer prevention through HPV vaccination and regular screening remains the cornerstone of public health efforts. This study specifically aims to evaluate the cost-effectiveness of various cervical cancer screening strategies (at different intervals) among WLHIV in India.

The study will be conducted in three interlinked components. First, a meta-analysis will be undertaken to evaluate the diagnostic accuracy of different screening strategies in detecting cervical lesions in WLHIV. Second, primary data collection will be carried out to estimate the treatment costs of cervical cancer and HIV among WLHIV. This phase will also include the collection of health-related quality of life (HRQoL) data, to inform utility estimates for the modelling component. A total of 135 participants will be enrolled for cost data assessment. Of these, a subset of 71 participants will also be included for HRQoL assessment. This data collection will be undertaken in four tertiary public sector hospitals located across four Indian states, that is, Mizoram, Maharashtra, Tamil Nadu and Karnataka. Lastly, a decision analytical model will be developed to simulate the process of screening, diagnosis and treatment for cervical cancer in a hypothetical cohort of WLHIV. A structured comprehensive review of literature will be undertaken to inform model input parameters related to the natural history of cervical disease, progression and mortality among WLHIV. Model calibration will be performed using a likelihood-based approach to ensure consistency with empirical epidemiological data. Probabilistic sensitivity analysis will also be conducted to assess the impact of joint parameter uncertainty on model outcomes.

Ethical approval has been obtained from Ethics Committees of Indian Council of Medical Research–National AIDS Research Institute (NARI), Pune (Protocol No. NARI/EC/Approval/2024/716); B. J. Medical College and Sassoon General Hospitals, Pune (Ref. No. BJGMC/IEC/Pharmac/ND-0824297-297); Cancer Institute (WIA), Adyar, Chennai (Ref. No. IEC/2024/Nov-07); the Mizoram State Cancer Institute, Zemabawk, Aizawl (Ref. No. D.12016/2/2013-MSCI/IEC) and the KLE Academy of Higher Education and Research, Belagavi, Karnataka. The study findings will be disseminated through publications in peer-reviewed journals.

The Quadrivalent human papillomavirus (HPV) Vaccine Evaluation Study with Addition of the Nonavalent Vaccine Study (QUEST-ADVANCE) aims to provide insight into the long-term immunogenicity and effectiveness of one, two and three HPV vaccine doses. Here, we describe the protocol for QUEST-ADVANCE.

QUEST-ADVANCE is an observational cohort study including males and females who are unvaccinated or vaccinated with the quadrivalent or nonavalent HPV vaccine in British Columbia, Canada. Female participants who are unvaccinated or vaccinated with 1–3 doses of the quadrivalent or nonavalent HPV vaccine at 9–14 years of age will be recruited approximately 5 or 12 years postvaccination eligibility. Male participants who are unvaccinated or vaccinated with 1 or 2 doses of the nonavalent HPV vaccine at 9–14 years of age will be recruited at approximately 5 years postvaccination eligibility. The study involves a maximum of four visits over a period of 4–5 years for female participants, and two visits over a 12-month period for male participants. At each visit, self-collected swabs (cervico-vaginal or penile) and questionnaire data will be collected. In each study group, a subset of participants will be invited to participate in a substudy evaluating the long-term humoral immunogenicity of the HPV vaccine. Additional blood samples will be collected from participants who are part of the immunogenicity substudy. The total required sample size is 7180 individuals. The primary objectives are (1) to examine vaccine effectiveness in males and females against prevalent genital HPV infections for one, two and three doses of the HPV vaccine compared with unvaccinated participants and (2) to evaluate if there is non-inferior immunogenicity as indicated by type-specific antibody response of one dose of the HPV vaccine in 20–27-year-old females vaccinated at 9–14 years of age compared with historical data of three doses of the HPV vaccine females vaccinated at 16–26 years of age up to 12 years postvaccination.

QUEST-ADVANCE was approved by the Research Ethics Board of the University of British Columbia/Children’s and Women’s Health Centre of British Columbia (H20-02111). Individual electronic informed consent or assent will be obtained from each participant before any study-specific procedures are undertaken. Results will be published in an international peer-reviewed journal and on the study website.