Table 1.
Characteristics of included studies
| Study | Location | Design | Study period | Inclusion criteria | Exclusion criteria | Age at enrolment (median (range)) | Duration of follow-up (median) | Vaccine/comparator | Study sponsorship | Conflict of interest | Number of participants | Outcomes |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Giuliano et al. 2011 [32] | Multicentre (18 countries) | RCT | 2004–ongoing (enrolled until 08/2008) | Heterosexual men 16–23 years of age who had 1–5 life-time sex partners or MSM 16–26 years. of age who had 1–5 male or female life-time sex partners | Men with clinically detectable anogenital warts or genital lesions or history of such findings | 20 years. (16–26 years) | 2.9 yrs | Gardasil/placebo | Merck; National Institutes of Health | Merck, GlaxoSmith-Kline (GSK), Qiagen, AstraZeneca | Vaccinated: 2032; placebo: 2033 | PIN grade 2 or 3; penile, perineal or perianal cancer; persistent anogenital infection; incident anogenital infection; genital condyloma acuminatum; severe adverse events |
| Palefsky et al. 2011 [33] | Multicentre (7 countries) | RCT (substudy of Giuliano et al. 2011 [32]) | 2004– ongoing (enrolled until 08/2008) | MSM 16–26 years. of age who had 1–5 male or female life-time sex partners and were engaged in insertive or receptive anal intercourse with another man in the past year | Men with history or presence of clinically detectable anogenital warts or genital lesions or intra-anal lesion on anoscopy consistent with AIN or condyloma | 22 years. (16–26 years) | 2.2 years | Gardasil/placebo | Merck; National Institutes of Health | Merck, GSK, Qiagen, Pharmajet, Aura Biosciences, Roche, GenProbe | Vaccinated: 301; placebo: 301 | AIN grade 2; AIN grade 3; anal cancer; persistent anal infection; incident anal infection; anal condyloma accuminatum; severe adverse events |
| Swedish et al. 2012 [25] | USA | Cohort study | 2007–2011 | MSM 18 years. or older with a history of biopsy-proven and treated high-grade AIN | Less than three vaccine doses; high-grade AIN at study start | 40.4 years. (20.3–72.3 years) | Vaccinated: 489 days; unvaccinated: 722 days | Gardasil/unvaccinated | NR | Merck, Qiagen, Asha | Vaccinated: 88; unvaccin-ated: 114 | Recurrent high-grade AIN (AIN grade 2 or 3) |
| Coskuner et al. 2014 [31] | Turkey | RCT (not placebo-controlled) | 2009–2013 | Men with new onset genital warts living in the same area for at least 1 year | Previous treatment for preexisting warts; medical disorders that needed chronic treatment; immune suppression (incl. HIV) | Mean: 34 years. (+/− 7.6) | 4 years after first dose | Gardasil/unvaccinated | NR | NR | Vaccinated: 91; unvaccinated: 80 | Recurrent condyloma acuminatum |
| Swedish and Goldstone 2014 [34] | USA | Cohort study | 2007–2013 (vaccinated until 2010) | Self-identified MSM, HIV-negative, no prior history of anal condyloma or previously treated anal condyloma but recurrence-free for at least 12 months prior to study entry | Men with anal or penile condyloma at study start | 42.2 years. (range 26.1–76 years) | Up to 4 years. (vacc: median 880 days; unvacc: median 1039 days) | Gardasil/unvaccinated | None | Merck | Vaccinated: 116; unvaccinated: 197 | Anal condyloma |
| Kahn et al. 2015 [24] | USA (5 centres) | Cross-sectional study | 2011–2012 | Youth with behaviorally acquired HIV | Serious psychiatric illness, intoxication with alcohol or drugs | 21.5 years. (range 12–24 years) | NA | Gardasil/unvaccinated | National Institutes of Health | Merck | Vaccinated: 23; unvaccinated: 48 | (Incident) oral infection (HPV 16 and/or HPV 18) |
| NCT01461096 [26, 47] | USA, Brazil | RCT | 2012–2015 (stopped due to futility) | HIV-infected adults | History of cancer, history of AIN, previous HPV vaccination, anticoagulation, allergies, drug/alcohol dependence, serious illness, immunomodulatory treatment; hepatitis B/C treatment | 47 years (intraquartile range: 41–53) | 2.1 years. (median) | Gardasil/placebo | National Institute of Allergy and Infectious Diseases | Gilead, Bristol Meyer Squibb, GSK | Vaccinated: 236; placebo: 236 | Persisting oral infectiona |
AIN anal intraepithelial neoplasia, MSM men who have sex with men, NA not applicable, NR not reported, PIN penile, perineal or perianal neoplasia, RCT randomized controlled trial
aData on other outcomes available for combined analysis of males and females