Research Article: Safety and immunogenicity of the quadrivalent human papillomavirus (qHPV) vaccine in HIV-positive Spanish men who have sex with men (MSM)

Date Published: July 18, 2017

Publisher: BioMed Central

Author(s): Carmen Hidalgo-Tenorio, Jessica Ramírez-Taboada, Concepción Gil-Anguita, Javier Esquivias, Mohamed Omar-Mohamed-Balgahata, Antonio SamPedro, Miguel Lopez-Ruz, Juan Pasquau.


Safety and immunogenicity of the quadrivalent human papillomavirus (qHPV) vaccine were evaluated in HIV-positive Spanish MSM. The prevalence of High Squamous Intraepithelial Lesions (HSIL) and genotypes of high-risk human papillomavirus (HR-HPV) were also determined, as well as risk factors associated with the presence of HR-HPV in anal mucosa.

This is a randomised, double blind, placebo-controlled trial of the quadrivalent HPV (qHPV) vaccine. The study enrolled from May 2012 to May 2014. Vaccine and placebo were administered at 0, 2 and 6 months (V1, V2, V3 clinical visits). Vaccine antibody titres were evaluated at 7 months. Cytology (Thin Prep® Pap Test), HPV PCR genotyping (Linear Array HPV Genotyping Test), and high-resolution anoscopy (Zeiss 150 fc© colposcope) were performed at V1.

Patients (n = 162; mean age 37.9 years) were screened for inclusion; 14.2% had HSIL, 73.1% HR-HPV and 4.5% simultaneous infection with HPV16 and 18. Study participants (n = 129) were randomized to qHPV vaccine or placebo. The most common adverse event was injection-site pain predominating in the placebo group [the first dose (83.6% vs. 56.1%; p = 0.0001]; the second dose (87.8% vs. 98.4%; p = 0.0001); the third dose (67.7% vs. 91.9%; p = 0.0001). The vaccine did not influence either the viral load of HIV or the levels of CD4. Of those vaccinated, 76% had antibodies to HPV vs. 30.2% of those receiving placebo (p = 0.0001). In the multivariate analysis, Older age was associated with lower HR-HPV infection (RR 0.97; 95% CI 0.96–0.99), and risk factor were viral load of HIV >200 copies/µL (RR 1.42 95% CI 1.17–1.73) and early commencement of sexual activity (RR 1.35; 95% CI 1.001–1.811).

This trial showed significantly higher anti-HR-HPV antibody titres in vaccinated individuals than in unvaccinated controls. There were no serious adverse events attributable to the vaccine. In our cohort, 1 of every 7 patients had HSIL and the prevalence of combined infection by genotypes 16 and 18 was low. This suggests that patients could benefit from receiving qHPV vaccine. Older age was the main protective factor against HR-HPV infection, and non-suppressed HIV viremia was a risk factor.

Partial Text

Anal squamous cell carcinoma (ASCC) in HIV patients is, currently, one of the most-frequent non-AIDS-defining cancers [1]. There are several studies that confirm its higher prevalence in HIV-positive individuals compared to the seronegative population; in one of them, the prevalence of anal HPV infection was 60% among HIV-negative men who have sex with men (MSM) and 93% among HIV-positive MSM [2]. However, its special relevance in HIV patients is not only due to its high prevalence, in MSM and women with cervical pathologies [3, 4], but also because of its greater rapidity of progression if not treated early. In a study carried out in Seattle, Washington, in MSM who were free of Anal intraepithelial neoplasia, High Squamous Intraepithelial Lesion (HSIL) developed in 15% of HIV-positive and 8% of HIV-negative men in an average of 21 months [5]. One of the risk factors implicated in the appearance of pre-malignant lesions (HSIL) and ASCC is the chronic infection by high-risk human papillomavirus (HR-HPV) genotypes [6, 7].

In this clinical trial conducted in Spanish HIV-positive MSM population, no patients had grade 3–4 adverse events (AE) related to the vaccine administration. The commonest AE was local injection-site pain which was more frequent in the placebo group. In a contrasting result [22] a different (vaccine adjuvant) placebo was used, but this result is negligible. There were no changes in the HIV viral load or levels of CD4 with any of the doses used, consistent with another study [25]. Finally, in another randomized, double-blind clinical trial that compared the bivalent vs. quadrivalent vaccine (Cervarix© vs. Gardasil©, is the one we employed) in HIV-infected adults; mild injection site reactions were more common in the Cervarix© group than in the Gardasil© group (91.1% vs. 69.6%; p = 0.02) and no serious EA occurred [32], despite the fact that both had a similar adjuvant.

This trial of qHPV vaccine conducted in Spanish HIV-positive MSM patients showed significantly higher anti-HR-HPV antibody titres in vaccinated individuals than in unvaccinated controls. There were no serious adverse events attributable to the vaccine. Although current prevalence of HPV 16/18 is low, a large proportion of men likely have had incident HPV 16/18 infections and cleared them; therefore, they may have natural immunity that protect against subsequent infection. Older age was the protective factor against HR-HPV infection and HIV no suppressed was the risk factor.




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