Natural History of Genital Warts: Analysis of the Placebo Arm of 2 Randomized Phase III Trials of a Quadrivalent Human Papillomavirus (Types 6, 11, 16, and 18) Vaccine

Background. The placebo arm of human papillomavirus (HPV) vaccine trials helps define the natural history of genital warts (GW). Methods. Women enrolled in the placebo arm (n = 8800) of 2 randomized trials of a quadrivalent vaccine were examined for the presence of GW for up to 9 visits over similar to 4 years. A comprehensive examination of the perianal area, vulva, and vagina prompted biopsy. Biopsy samples were analyzed by a blinded panel of up to 4 histopathologists and tested for 14 HPV genotypes (6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59) by use of a polymerase chain reaction-based assay. Risk factors for the development of GW were assessed. Results. Women were followed up for an average of 3.6 years (range, 0-4.9 years). Overall, 298 (3.4%) of 8800 participants developed GW related to HPV-6 or HPV-11 (incidence rate, 0.87 cases per 100 person-years-at-risk). In total, 520 distinct lesions were diagnosed as GW. HPV DNA was detected in 472 (90.8%) lesions, with HPV-6 and HPV-11 detected in 447 (86.0%) of these lesions (94.7% of 472 HPV DNA-positive lesions). We found high-risk HPV types in 161 (31.0%) of 520 lesions. Risk factors for HPV-6-and HPV-11-related GW included infection at baseline, acquisition of new sex partners, a higher number of sex partners, and DNA positivity at baseline for a high-risk HPV type. Conclusions. We confirm the major role played by HPV-6 and HPV-11 in GW, as well as associated risk factors. A vaccine that includes these types of HPV could substantially reduce the overall burden of HPV disease. Trial registration. Clinical Trials. gov identifiers: NCT00092521 and NCT00092534