Immunogenicity and safety of prophylactic HPV vaccines in people living with HIV: A systematic review and meta-analysis

Abstract

ABSTRACT Human papillomavirus (HPV) is a major global public health concern, causing genital warts and cancers of the cervix, anus, oropharynx, vulva, and penis. People living with HIV (PLWH) face a disproportionately elevated burden of HPV infection and HPV-related malignancies due to chronic immunosuppression. We conducted a systematic review and meta-analysis searching six databases from January 2006 to June 2026 without language restrictions. Twenty-five studies were included in the systematic review; 12 independent studies (N = 1,493 for HPV16) were included in the quantitative meta-analysis. Using a DerSimonian–Laird random-effects model with logit transformation, pooled seroconversion rates were: HPV16 97.8% (95% CI: 94.9–99.1%; I2 = 89.6%; 15 datasets), HPV18 94.2% (95% CI: 86.1–97.7%; I2 = 95.8%; 13 datasets), HPV6 97.0% (95% CI: 93.7–98.6%; I2 = 66.1%; 10 studies), and HPV11 97.1% (95% CI: 90.5–99.1%; I2 = 95.5%; 10 studies). CD4 count was the most consistently reported modifier of immunogenic response: HPV16 seroconversion was 98.5% in PLWH with CD4 > 350 cells/μL vs. 71.1% in those with CD4 ≤ 200 cells/μL (ACTG A5240). All three vaccine generations demonstrated high immunogenicity. Two doses of the nonavalent vaccine were non-inferior to three doses in virologically suppressed women (Papillon RCT). No vaccine-related serious adverse events were reported. GRADE certainty of evidence was moderate for HPV16, HPV6, and HPV11, and low for HPV18. Prophylactic HPV vaccination achieves high seroconversion rates across all vaccine generations in PLWH. CD4 count significantly modifies vaccine response, underscoring the importance of vaccination before severe immunosuppression develops. These findings support current international recommendations advocating HPV vaccination for all PLWH.