Effectiveness on high-grade cervical abnormalities and long-term safety of the quadrivalent human papillomavirus vaccine in Japanese women.

This study for the first time assessed quadrivalent human papillomavirus (qHPV) vaccine effectiveness against HPV6/11/16/18-related high-grade cervical disease in Japanese women (16-26 years old), as previously demonstrated in overseas trials, and vaccine safety in a longer term (48-month) open-label study (NCT01544478). Participants received three doses of qHPV vaccine (Day 1, Month 2, Month 6). Effectiveness endpoints, assessed in the per-protocol population, included incidence of HPV6/11/16/18-related cervical intraepithelial neoplasia (CIN) Grade 2 or worse (CIN Grade 2 and 3, adenocarcinoma in situ, and/or cervical cancer) as primary endpoint and incidence of external genital lesions (EGLs). Disease related to other high-risk HPV types was also assessed. Adverse events (AEs) and serious AEs (SAEs) were collected from Days 1-15 after any vaccination; vaccine-related SAEs, deaths, and new medical conditions were collected throughout the study. A total of 1030 women received at least one vaccination. No cases of CIN2 or worse or EGLs were reported in the per-protocol population. Injection site-related AEs were reported in 14.5% of participants; most were mild and resolved within 15 days. Vaccine-related systemic AEs occurred in 8.6% of participants, most commonly headache (2.3%), malaise (1.7%), and pyrexia (1.3%). There were no vaccine-related SAEs; one participant discontinued due to a vaccine-related AE of mild uticaria. Overall, qHPV vaccine effectiveness against HPV6/11/16/18-related high-grade cervical disease and EGLs was indicated in Japanese women. The vaccine was well-tolerated, without new safety signals throughout the 48-month study period. Findings are consistent with overseas qHPV vaccine pivotal trials. CLINICAL TRIAL REGISTRY: clinicaltrials.gov; NCT01544478.

Treatment of endometrial hyperplasia with a danazol-releasing intrauterine device: a prospective study.

The purpose of the present study was to assess the effect of a danazol-releasing intrauterine device (D-IUD) in the treatment of endometrial hyperplasia. Twenty patients with endometrial hyperplasia including 14 with simple endometrial hyperplasia and 2 with complex endometrial hyperplasia (group A), and 4 with atypical endometrial hyperplasia (group B) were enrolled in the prospective study between August 1999 and December 2003. During and just after the treatment, improvement was seen in all patients. Simple or complex endometrial hyperplasia (group A) demonstrated regression to a normal secretory endometrium (38% of group A), pseudodecidual stromal change (31%) and glandular atrophy (25%), and miscellaneous change (inflammation, necrosis, etc.) (38%). Atypical hyperplasia (group B) demonstrated regression to a normal secretory endometrium (25% of group B), pseudodecidual stromal change (75%), glandular atrophy (50%) and miscellaneous change (granulation) (25%). In group A, 2 women conceived after completion of the treatment. The recurrence rate in patients with endometrial hyperplasia (groups A and B) in the follow- up was 20% and acceptable as compared with other studies. The pretreatment menstrual interval patterns of the patients were maintained peri- and post-treatment. These data indicate that D-IUD therapy might be a novel and effective method for the treatment of endometrial hyperplasia.