BackgroundThe placebo arm of human papillomavirus (HPV) vaccine trials helps define the natural history of genital warts (GW) MethodsWomen 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 ∼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 ResultsWomen 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 ConclusionsWe 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 registrationClinicalTrials.gov identifiers: NCT00092521 and NCT00092534
Previous analyses from a randomized trial in women aged 24-45 have shown the quadrivalent HPV vaccine to be efficacious in the prevention of infection, cervical intraepithelial neoplasia (CIN) and ...external genital lesions (EGL) related to HPV 6/11/16/18 through 4 years. In this report we present long term follow-up data on the efficacy, safety and immunogenicity of the quadrivalent HPV vaccine in adult women.
Follow-up data are from a study being conducted in 5 sites in Colombia designed to evaluate the long-term immunogenicity, effectiveness, and safety of the qHPV vaccine in women who were vaccinated at 24 to 45 years of age (in the original vaccine group during the base study n = 684) or 29 to 50 years of age (in the original placebo group during the base study n = 651). This analysis summarizes data collected as of the year 6 post-vaccination visit relative to day 1 of the base study (median follow-up of 6.26 years) from both the original base study and the Colombian follow-up.
There were no cases of HPV 6/11/16/18-related CIN or EGL during the extended follow-up phase in the per-protocol population. Immunogenicity persists against vaccine-related HPV types, and no evidence of HPV type replacement has been observed. No new serious adverse experiences have been reported.
Vaccination with qHPV vaccine provides generally safe and effective protection from HPV 6-, 11-, 16-, and 18-related genital warts and cervical dysplasia through 6 years following administration to 24-45 year-old women.
Clinicaltrials.govNCT00090220.
Infection with human papillomavirus (HPV) serotypes 16 and 18 in men who have sex with men is a cause of considerable morbidity associated with anal intraepithelial neoplasia. This study shows that ...the HPV vaccine decreases the risk of HPV-associated anal disease.
Anal cancer is biologically similar to cervical cancer, including having a causal relationship with human papillomavirus (HPV) infection.
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Although HPV type 6 (HPV-6) or HPV type 11 (HPV-11) alone is rarely causal, the proportion of anal cancers associated with infection with HPV type 16 (HPV-16) or HPV type 18 (HPV-18) is as high as or higher than the proportion of cervical cancers.
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Just as cervical cancer is preceded by high-grade cervical intraepithelial neoplasia (grade ≥2), anal cancer is preceded by high-grade anal intraepithelial neoplasia (grade 2 or 3).
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Although not yet formally demonstrated, prevention or treatment of high-grade anal . . .
Limited data on the efficacy of the quadrivalent HPV vaccine are available for males. In this trial involving 4065 healthy boys and young men 16 to 26 years of age, the quadrivalent vaccine against ...HPV reduced the occurrence of external genital lesions by 60%.
Human papillomavirus (hpv) infects the squamous epithelium in both sexes, leading to anogenital condylomata acuminata and, in males, to cancers of the penis, anus, and oropharynx.
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The rate of genital HPV infection among males is similar to that in females. In any 12-month period, the probability that a sexually active male will acquire a new genital HPV infection is 0.29 to 0.39,
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which is similar to estimates for females. However, there are differences between the sexes in the immune response to HPV. A larger proportion of females are HPV-seropositive (17.9%, vs. 7.9% of males), and females . . .
Summary Background Although the peak incidence of human papillomavirus (HPV) infection occurs in most populations within 5–10 years of first sexual experience, all women remain at risk for ...acquisition of HPV infections. We tested the safety, immunogenicity, and efficacy of the quadrivalent HPV (types 6, 11, 16, 18) L1 virus-like-particle vaccine in women aged 24–45 years. Methods Women aged 24–45 years with no history of genital warts or cervical disease were enrolled from community health centres, academic health centres, and primary health-care providers into an ongoing multicentre, parallel, randomised, placebo-controlled, double-blind study. Participants were allocated by computer-generated schedule to receive quadrivalent HPV vaccine (n=1911) or placebo (n=1908) at day 1, and months 2 and 6. All study site investigators and personnel, study participants, monitors, and central laboratory personnel were blinded to treatment allocation. Coprimary efficacy endpoints were 6 months' or more duration of infection and cervical and external genital disease due to HPV 6, 11, 16, 18; and due to HPV 16 and 18 alone. Primary efficacy analyses were done in a per-protocol population, but intention-to-treat analyses were also undertaken. This study is registered with ClinicalTrials.gov , number NCT00090220. Findings 1910 women received at least one dose of vaccine and 1907 at least one dose of placebo. In the per-protocol population, efficacy against the first coprimary endpoint (disease or infection related to HPV 6, 11, 16, and 18) was 90·5% (95% CI 73·7–97·5, four of 1615 cases in the vaccine group vs 41/1607 in the placebo group) and 83·1% (50·6–95·8, four of 1601 cases vs 23/1579 cases) against the second coprimary endpoint (disease or infection related to HPV 16 and 18 alone). In the intention-to-treat population, efficacy against the first coprimary endpoint was 30·9% (95% CI 11·1–46·5, 108/1886 cases vs 154/1883 cases) and against the second coprimary endpoint was 22·6% (−2·9 to 41·9, 90/1886 cases vs 115/1883 cases), since infection and disease were present at baseline. We recorded no vaccine-related serious adverse events. Interpretation The quadrivalent HPV vaccine is efficacious in women aged 24–45 years not infected with the relevant HPV types at enrolment. Funding Merck (USA).
A quadrivalent human papillomavirus (HPV4) type 6/11/16/18 vaccine (GARDASIL/SILGARD®) has been licensed in many countries around the world for the prevention of cervical, vulvar, vaginal, and anal ...cancers and precancers, as well as external genital warts causally related to HPV types 6/11/16/18. Across 7 phase 3 clinical trials involving more than 29,000 males and females ages 9-45 years, vaccination was generally well tolerated. Because of its expected public health benefit in reducing cervical cancer and other HPV-related diseases, the vaccine has been implemented in the national vaccination programs of several countries, with over 178 million doses distributed worldwide.
Extensive efforts to assess the safety of the vaccine in routine practice have been conducted over the past 9 years since licensure, including more than 15 studies in more than 1 million preadolescents, adolescents and adults from various countries. Most have been performed in the general population although there have been some in special populations (pregnant women, HIV-infected individuals and those with systemic lupus erythematosus).
We present a summary of the published, postlicensure safety data from active and passive surveillance. Only syncope, and possibly skin infections were associated with vaccination in the postlicensure setting. Serious adverse events, such as adverse pregnancy outcomes, autoimmune diseases (including Guillain-Barre Syndrome and multiple sclerosis), anaphylaxis, venous thromboembolism and stroke, were extensively studied, and no increase in the incidence of these events was found compared with background rates.
These results, along with the safety data from the prelicensure clinical trials, confirm that the HPV4 vaccine has a favorable safety profile. Key policy, medical and regulatory organizations around the world have independently reviewed these data and continue to recommend routine HPV vaccination.
Background. We examined the baseline prevalence of penile, scrotal, perineal/perianal, and intra-anal human papillomavirus (HPV) infection in human immunodeficiency virus (HIV)—seronegative men who ...have sex with men (MSM). Methods. Data were analyzed from 602 MSM aged 16-27 years with ≤5 lifetime sexual partners. Serum samples were tested for antibodies to HPV6/11/16/18. Swab samples were collected separately from several anogenital areas for detection of HPV6/11/16/18/31/33/35/39/45/51/52/56/58/59 DNA. Results. The prevalence of any tested HPV type was 18.5% at the penis, 17.1% at the scrotum, 33.0% at the perineal/perianal region, 42.4% in the anal canal, and 48.0% at any site. Overall, 415 MSM (69.7%) were negative to HPV 6, 11, 16, and 18 at enrollment by both serology and DNA detection. Men residing in Europe and Latin America had significantly increased risk of HPV infection at external genital sites and the anal canal compared to men from Australia. Tobacco use and greater number of lifetime sexual partners was associated with higher HPV infection prevalence. Conclusions. The prevalence of HPV infection is high among young sexually active MSM, with the anal canal being the most common site of infection. Lifetime number of sexual partners was the most important modifiable risk factor for anogenital HPV infection.
Abstract Human papillomavirus (HPV) infection causes cervical cancer, a significant portion of anal, genital, and oropharyngeal cancers, genital warts, and recurrent respiratory papillomatosis. In ...June 2006, a quadrivalent HPV-6/11/16/18 vaccine (Gardasil/Silgard) was licensed in the United States, and subsequently in the European Union (September 2006). It has since been approved in 121 countries, with >74 million doses distributed globally as of March 2011. As the incidence of HPV infection peaks 5–10 years after the onset of sexual activity, preadolescents and adolescents represent an appropriate target group to implement HPV vaccination programs so as to achieve the maximal public health benefit. In this article, we provide an overview of the prophylactic efficacy of the vaccine in young women who were found to be negative to at least one of the four vaccine HPV types, thus approximating sexually naive adolescents. Because adolescents are also at high risk for other infections which are preventable by currently available vaccines, the development of concurrent immunization strategies may lead to better compliance, thereby contributing to the overall goal of protection against preventable diseases. We also summarize concomitant administration studies with meningococcal, diphtheria, tetanus, and pertussis vaccines, which were conducted in adolescents aged 9–15 years. Prophylactic efficacy in other populations (males aged 16–26 years) is also summarized along with long-term safety and efficacy studies.
Objectives To determine the effect of human papillomavirus (HPV) quadrivalent vaccine on the risk of developing subsequent disease after an excisional procedure for cervical intraepithelial neoplasia ...or diagnosis of genital warts, vulvar intraepithelial neoplasia, or vaginal intraepithelial neoplasia.Design Retrospective analysis of data from two international, double blind, placebo controlled, randomised efficacy trials of quadrivalent HPV vaccine (protocol 013 (FUTURE I) and protocol 015 (FUTURE II)).Setting Primary care centres and university or hospital associated health centres in 24 countries and territories around the world.Participants Among 17 622 women aged 15–26 years who underwent 1:1 randomisation to vaccine or placebo, 2054 received cervical surgery or were diagnosed with genital warts, vulvar intraepithelial neoplasia, or vaginal intraepithelial neoplasia.Intervention Three doses of quadrivalent HPV vaccine or placebo at day 1, month 2, and month 6.Main outcome measures Incidence of HPV related disease from 60 days after treatment or diagnosis, expressed as the number of women with an end point per 100 person years at risk.Results A total of 587 vaccine and 763 placebo recipients underwent cervical surgery. The incidence of any subsequent HPV related disease was 6.6 and 12.2 in vaccine and placebo recipients respectively (46.2% reduction (95% confidence interval 22.5% to 63.2%) with vaccination). Vaccination was associated with a significant reduction in risk of any subsequent high grade disease of the cervix by 64.9% (20.1% to 86.3%). A total of 229 vaccine recipients and 475 placebo recipients were diagnosed with genital warts, vulvar intraepithelial neoplasia, or vaginal intraepithelial neoplasia, and the incidence of any subsequent HPV related disease was 20.1 and 31.0 in vaccine and placebo recipients respectively (35.2% reduction (13.8% to 51.8%)).Conclusions Previous vaccination with quadrivalent HPV vaccine among women who had surgical treatment for HPV related disease significantly reduced the incidence of subsequent HPV related disease, including high grade disease.Trial registrations NCT00092521 and NCT00092534
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