HPV vaccination to prevent recurrence of anal intraepithelial neoplasia in HIV+ MSM

Abstract

Objective: Anal cancer precursor lesions high-grade anal intraepithelial neoplasia (HGAIN) are highly prevalent among HIV+ MSM. Treatment of HGAIN is frustrated by high recurrence rates. We investigated the efficacy of the quadrivalent human papillomavirus (qHPV) vaccine as posttreatment adjuvant in preventing HGAIN recurrence in HIV+ MSM. Design: Randomized, double-blind, placebo-controlled, multicentre trial. Setting: Three HIV outpatient clinics in Amsterdam, the Netherlands. Subjects: HIV+ MSM with CD4 + cell count more than 350 cells/μl, biopsy-proven intra-anal HGAIN successfully treated in the past year, and lesions still in remission at enrolment, as assessed by high-resolution anoscopy (HRA). Intervention: Participants were randomized to three doses of qHPV (Gardasil-4, MSD) or placebo with vaccinations at 0, 2, and 6 months. HRA was repeated at 6, 12, and 18 months. Main outcome measure: The primary outcome was cumulative, biopsy-proven HGAIN recurrence rate at 18 months, evaluated in an intention-to-treat (ITT) (received all vaccinations) and per-protocol analysis (all vaccinations and complete follow-up). Results: We randomized 126 participants of which 64 (50.8%) received qHPV and 62 (49.2%) placebo. All participants received three vaccinations, and in both groups for two participants follow-up was incomplete. We found no difference ( P = 0.38) in cumulative HGAIN recurrence rates between the qHPV (44/64, 68.8%) and placebo group (38/62, 61.3%) in the ITT analysis [absolute risk reduction −7.5 (95% confidence interval (CI) −24.1 to 9.2)]. This was similar in the per-protocol analysis. Conclusion: Despite adequate serological responses to qHPV vaccination, short-term recurrence of HGAIN was not prevented. These findings do not support qHPV vaccination as a treatment adjuvant to prevent HGAIN recurrence in HIV+ MSM.

Anal neoplasia: prevention or treatment?

“…At 48 months, there was no difference in the rates of HSIL between the two groups. These results are similar to the study by Gosens et al [15], but over a longer follow-up period and with no HSIL treatment. A previous large RCT of HIV-positive MSM (236; 82%) and women that had anal HSIL verified by biopsy (32-33% had HSIL) and HPV 16 or 18 detection (50% of total) at recruitment were followed up for vaccine efficiency in preventing persistent high-risk HPV infection or acquisition at the last visit [17].…”

“…Studies with nonovalent vaccine as a therapeutic agent are sparse. Given the cross-reactivity for HPV types 31 and 45 observed in the study by Gosens et al [15], nonovalent vaccine is unlikely to improve protection over the quadrivalent vaccine in secondary prevention.…”

“…In this issue, Gosens et al [15] carried out a RCT to see whether HPV vaccination might prevent future recurrences of anal HSIL in HIV-positive MSM who have had treatment for HSIL. A number of factors need consideration in designing a study of HSIL management.…”

“…The study by Gosens et al [15] is a useful addition to our understanding of factors related to anal cancer risk in HIV-positive MSM. Future research is needed to elucidate not only the role of protective immunity to high-risk HPV in infected individuals, but also the longterm effects of repetitive treatment of anal HSIL in anal cancer prevention.…”

Update on the Epidemiological Features and Clinical Implications of Human Papillomavirus Infection (HPV) and Human Immunodeficiency Virus (HIV) Coinfection

“…Regarding anal dysplasia in MSM living with HIV, several clinical trials failed to demonstrate a reduction in the recurrence of HPV-related dysplasia in this population [ 148 , 149 ]. In addition, to date, the relationship between HPV vaccination and the risk for oral and penile dysplasia remains unknown.…”