{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T11:16:11Z","timestamp":1784200571518,"version":"3.55.0"},"reference-count":26,"publisher":"Walter de Gruyter GmbH","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Studies of HPV vaccine efficacy usually record infections with vaccine targeted and non-targeted strains. Contrary to blinded randomized controlled trials, confounding bias can be a threat and risk compensation may occur in observational studies. Etievant et\u00a0al. (Biometrics, 2023) proposed to use cervical infections with non-targeted HPV strains to remove or reduce confounding bias in estimates of vaccine efficacy on targeted strains. However, they assumed that vaccinated women could not change their behavior after vaccination. This work investigates if the quantity estimated in practice with the method of Etievant et\u00a0al. has a clear causal meaning under a more plausible setting where unmeasured sexual behavior acts as both a confounder and a mediator. Under certain assumptions, using non-targeted HPV infections can remove both confounding bias and the portion of the vaccine effect on the targeted HPV strains that is mediated through the change of behavior. In that case, the estimated quantity has a clear causal interpretation as it represents the direct immunological effect of the vaccine. Infections with non-targeted HPV strains could also be used to isolate the indirect behavioral effect of the vaccine in unblinded randomized controlled trial.<\/jats:p>","DOI":"10.1515\/ijb-2025-0087","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T10:56:17Z","timestamp":1784199377000},"source":"Crossref","is-referenced-by-count":0,"title":["Using non-targeted HPV infections in\u00a0studies with\u00a0risk compensation"],"prefix":"10.1515","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7562-3550","authenticated-orcid":false,"given":"Lola","family":"Eti\u00e9vant","sequence":"first","affiliation":[{"name":"Universit\u00e9 Grenoble Alpes, CNRS, LJK , Grenoble , France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2026,7,16]]},"reference":[{"key":"2026071610561425483_j_ijb-2025-0087_ref_001","doi-asserted-by":"crossref","unstructured":"Porras, C, Sampson, JN, Herrero, R, Gail, MH, Cort\u00e9s, B, Hildesheim, A, et al.. Rationale and design of a double-blind randomized non-inferiority clinical trial to evaluate one or two doses of vaccine against human papillomavirus including an epidemiologic survey to estimate vaccine efficacy: the Costa Rica ESCUDDO trial. Vaccine 2022;40:76\u201388. https:\/\/doi.org\/10.1016\/j.vaccine.2021.11.041.","DOI":"10.1016\/j.vaccine.2021.11.041"},{"key":"2026071610561425483_j_ijb-2025-0087_ref_002","doi-asserted-by":"crossref","unstructured":"Basu, P, Malvi, SG, Joshi, S, Bhatla, N, Muwonge, R, Lucas, E, et al.. Vaccine efficacy against persistent human papillomavirus (HPV) 16\/18 infection at 10 years after one, two, and three doses of quadrivalent HPV vaccine in girls in India: a multicentre, prospective, cohort study. Lancet Oncol 2021;22:1518\u201329. https:\/\/doi.org\/10.1016\/s1470-2045(21)00453-8.","DOI":"10.1016\/S1470-2045(21)00453-8"},{"key":"2026071610561425483_j_ijb-2025-0087_ref_003","doi-asserted-by":"crossref","unstructured":"Fewell, Z, Davey Smith, G, Sterne, JA. The impact of residual and unmeasured confounding in epidemiologic studies: a simulation study. Am J Epidemiol 2007;166:646\u201355. https:\/\/doi.org\/10.1093\/aje\/kwm165.","DOI":"10.1093\/aje\/kwm165"},{"key":"2026071610561425483_j_ijb-2025-0087_ref_004","doi-asserted-by":"crossref","unstructured":"DiClemente, RJ. Validity of self-reported sexual behavior among adolescents: where do we go from here? AIDS Behav 2016;20:215\u201317. https:\/\/doi.org\/10.1007\/s10461-015-1217-5.","DOI":"10.1007\/s10461-015-1217-5"},{"key":"2026071610561425483_j_ijb-2025-0087_ref_005","doi-asserted-by":"crossref","unstructured":"M\u00e9ndez, F, Mu\u00f1oz, N, Posso, H, Molano, M, Moreno, V, Van Den Brule, AJ, et al.. Cervical coinfection with human papillomavirus (HPV) types and possible implications for the prevention of cervical cancer by HPV vaccines. J Infect Dis 2005;192:1158\u201365. https:\/\/doi.org\/10.1086\/444391.","DOI":"10.1086\/444391"},{"key":"2026071610561425483_j_ijb-2025-0087_ref_006","doi-asserted-by":"crossref","unstructured":"Chaturvedi, AK, Katki, HA, Hildesheim, A, Rodr\u00edguez, AC, Quint, W, Schiffman, M, et al.. Human papillomavirus infection with multiple types: pattern of coinfection and risk of cervical disease. J Infect Dis 2011;203:910\u201320. https:\/\/doi.org\/10.1093\/infdis\/jiq139.","DOI":"10.1093\/infdis\/jiq139"},{"key":"2026071610561425483_j_ijb-2025-0087_ref_007","doi-asserted-by":"crossref","unstructured":"Etievant, L, Sampson, JN, Gail, MH. Increasing efficiency and reducing bias when assessing HPV vaccination efficacy by using nontargeted HPV strains. Biometrics 2023;79:1534\u201345. https:\/\/doi.org\/10.1111\/biom.13663.","DOI":"10.1111\/biom.13663"},{"key":"2026071610561425483_j_ijb-2025-0087_ref_008","doi-asserted-by":"crossref","unstructured":"Lipsitch, M, Tchetgen, ET, Cohen, T. Negative controls: a tool for detecting confounding and bias in observational studies. Epidemiology 2010;21:383\u20138. https:\/\/doi.org\/10.1097\/ede.0b013e3181d61eeb.","DOI":"10.1097\/EDE.0b013e3181d61eeb"},{"key":"2026071610561425483_j_ijb-2025-0087_ref_009","doi-asserted-by":"crossref","unstructured":"Wilde, GJ. Risk homeostasis theory: an overview. Inj Prev 1998;4:89\u201391. https:\/\/doi.org\/10.1136\/ip.4.2.89.","DOI":"10.1136\/ip.4.2.89"},{"key":"2026071610561425483_j_ijb-2025-0087_ref_010","doi-asserted-by":"crossref","unstructured":"Hedlund, J. Risky business: safety regulations, risk compensation, and individual behavior. 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JAIDS J Acquir Immune Defic Syndr 2007;44:66\u201370. https:\/\/doi.org\/10.1097\/01.qai.0000242455.05274.20.","DOI":"10.1097\/01.qai.0000242455.05274.20"},{"key":"2026071610561425483_j_ijb-2025-0087_ref_021","doi-asserted-by":"crossref","unstructured":"White, RG, Glynn, JR, Orroth, KK, Freeman, EE, Bakker, R, Weiss, HA, et al.. Male circumcision for HIV prevention in sub-Saharan Africa: who, what and when? AIDS 2008;22:1841\u201350. https:\/\/doi.org\/10.1097\/qad.0b013e32830e0137.","DOI":"10.1097\/QAD.0b013e32830e0137"},{"key":"2026071610561425483_j_ijb-2025-0087_ref_022","doi-asserted-by":"crossref","unstructured":"Dema, E, Shing, JZ, Checchi, M, Beddows, S, Liu, D, Sierra, MS, et al.. Developing, validating, and testing non-vaccine \u2013 preventable human papillomavirus to control for differences in sexual behavior when evaluating HPV vaccination. Cancer Epidemiol Biomarkers Prev 2025;34:1093\u2013102. https:\/\/doi.org\/10.1158\/1055-9965.epi-24-1775.","DOI":"10.1158\/1055-9965.EPI-24-1775"},{"key":"2026071610561425483_j_ijb-2025-0087_ref_023","doi-asserted-by":"crossref","unstructured":"Ioannidis, JP. Benefit of COVID-19 vaccination accounting for potential risk compensation. NPJ Vaccines 2021;6:99. https:\/\/doi.org\/10.1038\/s41541-021-00362-z.","DOI":"10.1038\/s41541-021-00362-z"},{"key":"2026071610561425483_j_ijb-2025-0087_ref_024","doi-asserted-by":"crossref","unstructured":"McColl, K, Martin-Lapoirie, D, Veltri, GA, Arwidson, P, Raude, J. Does vaccination elicit risk compensation? Insights from the COVID-19 pandemic in France. Health Psychol Behav Med 2024;12:2287663. https:\/\/doi.org\/10.1080\/21642850.2023.2287663.","DOI":"10.1080\/21642850.2023.2287663"},{"key":"2026071610561425483_j_ijb-2025-0087_ref_025","doi-asserted-by":"crossref","unstructured":"Smart, SJ, Polachek, SW. COVID-19 vaccine and risk-taking. 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