Human Papillomavirus–Related Cancer in People With HIV and Solid Organ Transplant Recipients

Importance: Human papillomavirus (HPV)-related cancers cause substantial morbidity and mortality. People with HIV (PWH) and solid organ transplant recipients (SOTRs) are at heightened risk due to impaired immune function, but direct comparisons of these groups within the same population are limited; understanding the relative risk and contributing factors is essential for targeted prevention and screening. Objective: To compare the odds of HPV-related cancers in PWH and SOTRs with control participants and assess how clinical and sociodemographic factors modify these associations. Design, Setting, and Participants: This nested case-control study used incidence density sampling within the Swedish population. Individuals born between 1940 and 2000 and who were a resident of Sweden from 1983 to 2024 were included. HPV-related cancer cases were matched 1:10 with controls based on sex, year of birth, and region of birth. Exposure: HIV infection or history of organ transplant. Main Outcome and Measures: The primary outcome was HPV-related cancers, identified via diagnostic codes from the Swedish Cancer Registry. Odds ratios (ORs) with 95% CIs of HPV-related cancers by immunosuppression were estimated using conditional logistic regression. In secondary analyses, comparisons were stratified by sex, age at cancer diagnosis, calendar period of diagnosis, HPV-related cancer site, region of birth, education, income, income type, and civil status. Results: The study included 32 093 cases (21 206 female [65.5%]; 12 534 aged <50 years [39.4%]) and 320 930 matched control encounters (308 507 unique individuals; 201 667 female [65.4%]; 122 055 aged <50 years). Both PWH and SOTRs had elevated odds of HPV-related cancers compared with controls (PWH: adjusted OR [aOR], 4.50; 95% CI, 3.46-5.84; SOTRs: aOR, 2.23; 95% CI, 1.85-2.68). Among PWH, the highest site-specific odds were observed for anal (aOR, 58.79; 95% CI, 22.63-152.79) and penile (aOR, 8.05; 95% CI, 3.38-19.16) cancer. Among SOTRs, the highest odds were for vulvar (aOR, 7.07; 95% CI, 4.31-11.60) and penile (aOR, 6.01; 95% CI, 3.47-10.52) cancers, with variation by organ sites and time since transplant (>10 years posttransplant). In PWH, lower nadir (aOR 5.90; 95% CI, 4.04-8.61) and current (aOR, 8.62; 95% CI, 3.70-20.04) CD4 counts, shorter duration of viral suppression (aOR, 7.04; 95% CI, 4.40-11.27), and higher peak plasma HIV RNA levels (aOR, 5.66; 95% CI, 2.96-10.84) were associated with increased odds. In secondary analyses, sociodemographic factors such as lower income and nonmarried status were associated with elevated odds in both groups. Conclusions and Relevance: In this case-control study of immunosuppressed populations, HPV-related cancer odds were increased among both PWH and SOTRs, with larger magnitudes of association observed in PWH; variation was observed by immune status, transplant characteristics, and sociodemographic factors. These findings highlight the need for enhanced prevention, including HPV vaccination, screening, and optimized immunosuppressive regimens.