BackgroundHuman papillomavirus (HPV)–6/11/16/18 vaccine reduces the risk of HPV-6/11/16/18–related cervical intraepithelial neoplasia (CIN) 1–3 or adenocarcinoma in situ (AIS). Here, its impact on ...CIN1–3/AIS associated with nonvaccine oncogenic HPV types was evaluated MethodsWe enrolled 17,622 women aged 16–26 years. All underwent cervicovaginal sampling and Pap testing at regular intervals for up to 4 years. HPV genotying was performed for biopsy samples, and histological diagnoses were determined by a pathology panel. Analyses were conducted among subjects who were negative for 14 HPV types on day 1. Prespecified analyses included infection of ⩾6 months’ duration and CIN1–3/AIS due to the 2 and 5 most common HPV types in cervical cancer after HPV types 16 and 18, as well as all tested nonvaccine types ResultsVaccination reduced the incidence of HPV-31/45 infection by 40.3% (95% confidence interval CI, 13.9% to 59.0%) and of CIN1–3/AIS by 43.6% (95% CI, 12.9% to 64.1%), respectively. The reduction in HPV-31/33/45/52/58 infection and CIN1–3/AIS was 25.0% (95% CI, 5.0% to 40.9%) and 29.2% (95% CI, 8.3% to 45.5%), respectively. Efficacy for CIN2–3/AIS associated with the 10 nonvaccine HPV types was 32.5% (95% CI, 6.0% to 51.9%). Reductions were most notable for HPV-31 ConclusionsHPV-6/11/16/18 vaccine reduced the risk of CIN2–3/AIS associated with nonvaccine types responsible for ∼20% of cervical cancers. The clinical benefit of cross-protection is not expected to be fully additive to the efficacy already observed against HPV-6/11/16/18–related disease, because women may have >1 CIN lesion, each associated with a different HPV type Trial registrationClinicalTrials.gov identifiers: NCT00092521, NCT00092534, and NCT00092482
Summary
European treatment guidelines for hepatitis C virus (HCV) infection recommend that people with genotype (GT) 1a infection and baseline viral load ≤800 000 IU/mL receive elbasvir/grazoprevir ...(EBR/GZR) for 12 weeks, and those with baseline viral load >800 000 IU/mL receive EBR/GZR plus ribavirin for 16 weeks. This analysis was conducted to clarify whether baseline viral load can serve as an accurate, sensitive or specific stratification factor for defining EBR/GZR regimens. In this post hoc, integrated analysis, participants with GT1a infection who received EBR 50 mg/GZR 100 mg for 12 weeks were stratified according to baseline viral load. Sustained virologic response at 12 weeks post‐treatment was achieved by 95.2% (911/957) of participants and was higher among participants with baseline viral load ≤800 000 IU/mL vs >800 000 IU/mL (98.5% vs 93.9%). The 800 000 IU/mL threshold had a positive predictive value of 98.5%, a negative predictive value of 6.1%, a specificity of 91.3%, a sensitivity of 28.4% and an overall accuracy of 31.5%. A baseline viral load cutpoint of 800 000 IU/mL had high positive predictive value and specificity but poor negative predictive value, sensitivity and accuracy in predicting treatment outcomes in this population. Baseline NS5A resistance‐associated substitutions (RASs) were detected in 25% (1/4) of virologic failures with baseline viral load ≤800 000 IU/mL and 59.5% (25/42) of those with baseline viral load >800 000 IU/mL. Overall, these data suggest that, compared with the use of a baseline viral load cutpoint, baseline testing for NS5A RASs enables more individuals to receive the 12‐week EBR/GZR regimen without compromising the opportunity for SVR.
Background & Aims
The aim of this integrated analysis was to assess the efficacy of the once‐daily combination of elbasvir 50 mg and grazoprevir 100 mg, with and without ribavirin in HCV genotype 4 ...(GT4)‐infected participants enrolled in the Phase 2/3 clinical programme with elbasvir/grazoprevir.
Methods
Treatment‐naïve and treatment‐experienced participants 18 years of age or older with chronic HCV GT4 infection and baseline HCV RNA ≥10 000 IU/mL were included in the analysis. The analysis population was the full analysis set (FAS; all participants who received at least 1 dose of study medication) and a total of 155 HCV GT4 participants were evaluated. The primary endpoint was sustained virologic response at week 12 (SVR12; HCV RNA less than the lower limit of quantitation at 12 weeks after the completion of study therapy).
Results
Overall, among GT4‐infected participants treated with 12 or 16 weeks of elbasvir/grazoprevir ± ribavirin, the SVR12 efficacy rates were 96.4% (107/111) in treatment‐naïve participants and 88.6% (39/44) in treatment‐experienced participants. The SVR12 rates were 96.0% (97/101) in treatment‐naïve participants treated with 12 weeks of elbasvir/grazoprevir and 100% (8/8) in treatment‐experienced participants treated with 16 weeks of elbasvir/grazoprevir plus ribavirin. Efficacy was not impacted by GT4 subtype.
Conclusions
The regimens of 12 weeks of elbasvir/grazoprevir without ribavirin, and 16 weeks of elbasvir/grazoprevir plus ribavirin, were efficacious in HCV GT4‐infected treatment‐naïve and treatment‐experienced participants respectively. Baseline NS5A resistance‐associated substitutions did not impact the efficacy of elbasvir/grazoprevir in GT4‐infected participants.
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.
Human papillomavirus (HPV) virus-like particle (VLP) vaccines have demonstrated effectiveness in preventing persistent HPV infections. Whether protection lasts longer than 18 months and, thus, ...impacts rates of cervical intraepithelial neoplasia (CIN) 2-3 has not yet been established. We present results from an HPV16 L1 VLP vaccine trial through 48 months.
A total of 2,391 women, aged 16-23 years, participated in a randomized, double-blind, placebo-controlled trial. Either 40 mug HPV16 L1 VLP vaccine or placebo was given intramuscularly at day 1, month 2, and month 6. Genital samples for HPV16 DNA and Pap tests were obtained at day 1, month 7, and then 6-monthly through month 48. Colposcopy and cervical biopsies were performed if clinically indicated and at study exit. Serum HPV16 antibody titer was measured by radioimmunoassay.
Among 750 placebo recipients in the per protocol population, 12 women developed HPV16-related CIN2-3 (6 CIN2 and 6 CIN3). Among 755 vaccine recipients, there were no cases (vaccine efficacy 100%, 95% confidence interval CI 65-100%). There were 111 cases of persistent HPV16 infection in placebo recipients and 7 cases in vaccine recipients (vaccine efficacy 94%, 95% CI 88-98%). After immunization, HPV16 serum antibody geometric mean titers peaked at month 7 (1,519 milli-Merck units mMU/mL), declined through month 18 (202 mMU/mL), and remained relatively stable between month 30 and month 48 (128-150 mMU/mL).
The vaccine HPV16 L1 VLP provides high-level protection against persistent HPV16 infection and HPV16-related CIN2-3 for at least 3.5 years after immunization. Administration of L1 VLP vaccines targeting HPV16 is likely to reduce risk for cervical cancer.
I.
A randomised double-blind placebo-controlled phase II study was done to assess the efficacy of a prophylactic quadrivalent vaccine targeting the human papillomavirus (HPV) types associated with 70% ...of cervical cancers (types 16 and 18) and with 90% of genital warts (types 6 and 11).
277 young women (mean age 20·2 years SD 1·7) were randomly assigned to quadrivalent HPV (20 μg type 6, 40 μg type 11, 40 μg type 16, and 20 μg type 18) L1 virus-like-particle (VLP) vaccine and 275 (mean age 20·0 years 1·7) to one of two placebo preparations at day 1, month 2, and month 6. For 36 months, participants underwent regular gynaecological examinations, cervicovaginal sampling for HPV DNA, testing for serum antibodies to HPV, and Pap testing. The primary endpoint was the combined incidence of infection with HPV 6, 11, 16, or 18, or cervical or external genital disease (ie, persistent HPV infection, HPV detection at the last recorded visit, cervical intraepithelial neoplasia, cervical cancer, or external genital lesions caused by the HPV types in the vaccine). Main analyses were done per protocol.
Combined incidence of persistent infection or disease with HPV 6, 11, 16, or 18 fell by 90% (95% CI 71–97, p<0·0001) in those assigned vaccine compared with those assigned placebo.
A vaccine targeting HPV types 6, 11, 16, 18 could substantially reduce the acquisition of infection and clinical disease caused by common HPV types.
Published online April 7, 2005 DOI 10.1016/S1470-2045(05)70101-7
BackgroundWe evaluated the impact of a quadrivalent human papillomavirus (HPV) vaccine on infection and cervical disease related to 10 nonvaccine HPV types (31, 33, 35, 39, 45, 51, 52, 56, 58, and ...59) associated with >20% of cervical cancers. The population evaluated included HPV-naive women and women with preexisting HPV infection and/or HPV-related disease at enrollment MethodsPhase 3 efficacy studies enrolled 17,622 women aged 16–26 years. Subjects underwent cervicovaginal sampling and Pap testing on day 1 and then at 6–12-month intervals for up to 4 years. HPV typing was performed on samples from enrollment and follow-up visits, including samples obtained for diagnosis or treatment of HPV-related disease. All subjects who received ⩾1 dose and returned for follow-up were included ResultsVaccination reduced the rate of HPV-31/33/45/52/58 infection by 17.7% (95% confidence interval CI, 5.1% to 28.7%) and of cervical intraepithelial neoplasia (CIN) 1–3 or adenocarcinoma in situ (AIS) by 18.8% (95% CI, 7.4% to 28.9%). Vaccination also reduced the rate of HPV-31/58/59–related CIN1–3/AIS by 26.0% (95% CI, 6.7% to 41.4%), 28.1% (95% CI, 5.3% to 45.6%), and 37.6% (95% CI, 6.0% to 59.1%), respectively. Although a modest reduction in HPV-31/33/45/52/58–related CIN2 or worse was observed, the estimated reduction was not statistically significant ConclusionsThese cross-protection results complement the vaccine’s prophylactic efficacy against disease associated with HPV-6, -11, -16, and -18. Long-term monitoring of vaccinated populations are needed to fully ascertain the population-based impact and public health significance of these findings Trial registrationClinicalTrials.gov identifiers: NCT00092521, NCT00092534, and NCT00092482
The lifetime risk of human papillomavirus (HPV) infection exceeds 50%. HPV infection causes >550,000 cases of cervical and anogenital cancer worldwide annually. Infection also causes precancerous ...lesions and genital warts. HPV types 16 and 18 cause ∼70% of HPV-related cancers, and HPV types 6 and 11 cause ∼90% of cases of genital warts. A quadrivalent vaccine for HPV types 6, 11, 16, and 18 (HPV 6/11/16/18) has been developed for prevention of cervical cancer, genital warts, and vulvar and vaginal precancerous lesions. Prophylactic vaccination of young women was 96%-100% effective in preventing HPV 6/11/16/18-related cervical and anogenital precancers and genital warts. Efficacy remained high for at least 5 years following vaccination. Postvaccination anti-HPV levels in adolescents were superior to those observed in women (the population in which efficacy was shown). Vaccination was generally well tolerated. The vaccine is licensed in >80 countries. It has been added to national vaccination programs, including that of the United States. Widespread use of HPV 6/11/16/18 vaccine is expected to greatly reduce the incidence of HPV-related cancers, precancers, and genital warts.
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