High Prevalence of Anal High-Grade Squamous Intraepithelial Lesions, and Prevention Through Human Papillomavirus Vaccination, in Young Men Who Have Sex With Men Living With Human Immunodeficiency Virus

Abstract

Background: Men who have sex with men (MSM) are at high risk for human papillomavirus (HPV)-related anal cancer. Little is known about the prevalence of low-grade squamous intraepithelial lesions (LSILs) and the anal cancer precursor, high-grade squamous intraepithelial lesions (HSILs), among young MSM with HIV (MSMLWH). HPV vaccination is recommended in this group, but its safety, immunogenicity, and protection against vaccine-type HPV infection and associated LSILs/HSILs have not been studied.

Methods: Two hundred and sixty MSMLWH aged 18-26 years were screened at 17 US sites for a clinical trial of the quadrivalent (HPV6,11,16,18) HPV (qHPV) vaccine. Those without HSILs were vaccinated at 0, 2, and 6 months. Cytology, high-resolution anoscopy with biopsies of lesions, serology, and HPV testing of the mouth/penis/scrotum/anus/perianus were performed at screening/month 0 and months 7, 12, and 24.

Results: Among 260 MSMLWH screened, the most common reason for exclusion was detection of HSILs in 88/260 (34%). 144 MSMLWH were enrolled. 47% of enrollees were previously exposed to HPV16. No incident qHPV type-associated anal LSILs/HSILs were detected among men naive to that type, compared with 11.1, 2.2, 4.5, and 2.8 cases/100 person-years for HPV6,11,16,18-associated LSILs/HSILs, respectively, among those previously exposed to that type. qHPV was immunogenic and safe with no vaccine-associated serious adverse events.

Conclusions: 18-26-year-old MSMLWH naive to qHPV vaccine types were protected against incident qHPV type-associated LSILs/HSILs. Given their high prevalence of HSILs, there is an urgent need to vaccinate young MSMLWH before exposure to vaccine HPV types, before initiating sexual activity, and to perform catch-up vaccination.

Keywords: anal human papillomavirus infection; anal squamous intraepithelial lesions; human immunodeficiency virus; men who have sex with men; quadrivalent HPV vaccine.

Figure 1.

Participant flow in AMC-072. *Four patients were enrolled in error: No treatment per protocol criteria (n = 1), HPV vaccine prior to screening (n = 1), AIN 3 on screening (n = 1), not on HAART for 90 days prior to entry (n = 1). **One patient withdrew/refused prior to beginning protocol therapy. Abbreviations: AE, adverse event; alc, alcohol; AMC, AIDS Malignancy Consortium; AIN, Anal intraepithelial neoplasia; ANC, Absolute neutrophil count; HAART, highly active antiretroviral therapy; HPV, human papillomavirus; LTFU, lost to follow-up.

Figure 2.

Geometric mean (95% confidence interval) titers to HPV 6 (A), 11 (B), 16 (C), and 18 (D) among naive and previously exposed 18–26-year-old men who have sex with men living with HIV, up to 2 years after initiation of vaccination. Titers in participants naive to a qHPV vaccine HPV type are shown in blue. Titers in participants previously exposed to that HPV type are shown in red. Abbreviations: GMT, geometric mean titer; HIV, human immunodeficiency virus; HPV, human papillomavirus; qHPV, quadrivalent human papillomavirus. Asterisks show when vaccine doses were administered.