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) |
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 |