Prevention of Anal Condyloma with Quadrivalent Human Papillomavirus Vaccination of Older Men Who Have Sex with Men

Goldstone SE (2014) Prevention of Anal Condyloma with Quadrivalent Human Papillomavirus Vaccination of Older Men Who Have Sex with Men. PLoS ONE 9(4): e93393. doi:10.1371/journal.pone.0093393 Prevention of Anal Condyloma with Quadrivalent Human Papillomavirus Vaccination of Older Men Who Have Sex with Men Kristin A. Swedish 0 Stephen E. Goldstone 0 Marcia E. Lopes Consolaro, State University of Maringa/Universidade Estadual de Maringa, Brazil 0 1 Department of Internal Medicine, Montefiore Medical Center, Bronx, New York, United States of America, 2 Department of Surgery, Icahn School of Medicine at Mount Sinai , New York, New York , United States of America Background: The quadrivalent human papillomavirus vaccine (qHPV) is FDA-approved for use in males 9 to 26 years old to prevent anogenital condyloma. The objective of this study is to determine if qHPV is effective at preventing anal condyloma among men who have sex with men (MSM) aged 26 years and older. Methods: This post-hoc analysis of a nonconcurrent cohort study evaluated 210 patients without history of anal condyloma and 103 patients with previously-treated anal condyloma recurrence-free for at least 12 months prior to vaccination/time zero. We determined the rate of anal condyloma development in vaccinated versus unvaccinated patients. Results: 313 patients with mean age 42 years were followed for median 981 days. During 773.6 person-years follow-up, condyloma developed in 10 (8.6%) vaccinated patients (incidence of 3.7 per 100 person-years) and 37 (18.8%) unvaccinated patients (incidence 7.3 per 100 person-years; p = 0.05). Multivariable hazards ratio showed that qHPV was associated with decreased risk of anal condyloma development (HR 0.45; 95% CI 0.22-0.92; p = 0.03). History of anal condyloma was associated with increased risk of anal condyloma development (HR 2.28; 95% CI 1.28-4.05; p = 0.005), as was infection with oncogenic HPV (HR 3.87; 95% CI 1.66-9.03; p = 0.002). Conclusions: Among MSM 26 years of age and older with and without history of anal condyloma, qHPV reduces the risk of anal condyloma development. A randomized controlled trial is needed to confirm these findings in this age group. - Anogenital condyloma affect approximately 1% of the American sexually active population at any one time[1] and are more prevalent among men who have sex with men (MSM) than among men who have sex with women. A study of over 2000 men aged 16 to 26 found the incidence rate of anogenital condyloma was more than three times higher among MSM than men who identified as heterosexual (4.7 per 100 person-years vs. 1.5 per 100 personyears; unpublished data). An international study of men aged 18 to 70 found that men with 3 or more male anal sex partners in the past 3 months were 4.5 times more likely than men with no male partners to develop anogenital condyloma[2]. The quadrivalent HPV vaccine (qHPV; Gardasil, Merck & Co., Inc, Whitehouse Station, NJ) protects against the 4 most common HPV types, including non-oncogenic types HPV 6 and 11, which account for approximately 90% of all anogenital condyloma[3]. In their study of qHPV among young men aged 16 to 26 without history of anogenital condyloma, Giuliano et al. found that qHPV was 89% effective against condyloma development in those PCR and seronegative for the 4 qHPV types at baseline. However, the vaccine was shown to be more effective among heterosexual males (92% efficacy) than MSM (79% efficacy; against external genital lesions, the majority of which were condyloma). In the intentionto-treat population (heterosexual males and MSM who may not have received all 3 doses of qHPV and/or may have been PCR or seropositive for any of the 4 qHPV types at baseline), efficacy to prevent condyloma dropped to 67% [4]. Based upon the results of this clinical trial, the United States Food and Drug Administration licensed qHPV for use in males 9 to 26 years old to prevent anogenital condyloma caused by HPV 6 and 11[5]. In a substudy of just MSM aged 1626, qHPV demonstrated 100% efficacy preventing intra-anal condyloma in subjects PCR and seronegative for the 4 qHPV types and 57.2% in the intention to treat population[6]. Further analysis limited to men who were seronegative for the 4 qHPV types and PCR-negative to 10 non-qHPV types found 85% efficacy of qHPV against condyloma. In the intention-to-treat population (men who may not have received all 3 doses of qHPV and/or may have been PCR or seropositive for any of the 14 HPV types at baseline), qHPV efficacy against external genital lesions decreased to 59%[7]. Although the incidence and prevalence of anogenital condyloma in men decreases with age[2,8,9], older MSM remain at risk for their development. Although not associated with increased mortality, condyloma are a source of emotional distress and affect quality of life[10]. Treatment is expensive, estimated to cost over $800 per incident case in the United States[11]. Recurrence, defined as reappearance of condyloma within 12 months after complete clearance, ranges from 4% to 50%, depending on treatment modality and immune competence[12,13]. In one private practice (SEG), all HIV-negative MSM were offered qHPV off-label regardless of age, history of anogenital condyloma, history of anal high-grade squamous intraepithelial lesion (HSIL), or prior HPV infection. Insurance typically did not cover the cost of the vaccine; many patients paid out of pocket. The following is a non-concurrent observational cohort study evaluating the effectiveness of qHPV in preventing anal condyloma among HIVnegative MSM patients 26 years of age and older in this practice. Study Population and Data Collection The methodology of this study has been reported elsewhere[14]. Briefly, study participants were recruited from a single anorectal surgery practice (SEG) in New York City that specializes in screening, diagnosis, and treatment of anorectal diseases. The majority of patients are MSM presenting with HPV related disease. Beginning in June 2006, the three-dose qHPV series was offered off-label to all HIV-negative MSM patients at each clinical visit. This post-hoc analysis included patients who were 26 years of age or older, HIV-negative, and self-identified MSM. Patients were included if they had no prior history of anal condyloma or if they had previously-treated anal condyloma and were recurrencefree for at least 12 months prior to study entry. Medical charts of all eligible patients seen during 20072010 were screened for inclusion. Study patients were identified as exposed to vaccination when billing records found payment for all 3 qHPV doses and the medical record noted vaccination. Study patients were identified as unvaccinated when billing records showed no qHPV doses and the medical record did not indicate vaccination. Patients who did not receive all 3 doses of the vaccine or who were vaccinated elsewhere were excluded. As with our prior study, vaccinated patients entered the s (...truncated)