A profound prolongation of UNB of ∼60% was detected with perineural dexmedetomidine when added to 0.75% ropivacaine. The systemic administration of 20 µg dexmedetomidine resulted in a prolongation of ∼10% during UNB with 0.75% ropivacaine. Eudra-CT No.: 2012-000030-19.

The overall safety profile of the 9-valent human papillomavirus (9vHPV) vaccine was evaluated across 7 Phase III studies, conducted in males and females (nonpregnant at entry), 9 to 26 years of age. METHODS:Vaccination was administered as a 3-dose regimen at day 1, and months 2 and 6. More than 15 000 subjects received ≥1 dose of 9vHPV vaccine. In 2 of the studies, >7000 control subjects received ≥1 dose of quadrivalent HPV (qHPV) vaccine. Serious and nonserious adverse events (AEs) and new medical conditions were recorded throughout the study. Subjects testing positive for pregnancy at day 1 were not vaccinated; those who became pregnant after day 1 were discontinued from further vaccination until resolution of the pregnancy. Pregnancies detected after study start (n = 2950) were followed to outcome. RESULTS:The most common AEs (≥5%) experienced by 9vHPV vaccine recipients were injection-site AEs (pain, swelling, erythema) and vaccine-related systemic AEs (headache, pyrexia). Injection-site AEs were more common in 9vHPV vaccine than qHPV vaccine recipients; most were mild-to-moderate in intensity. Discontinuations and vaccine-related serious AEs were rare (0.1% and <0.1%, respectively). Seven deaths were reported; none were considered vaccine related. The proportions of pregnancies with adverse outcome were within ranges reported in the general population. CONCLUSIONS:The 9vHPV vaccine was generally well tolerated in subjects aged 9 to 26 years with an AE profile similar to that of the qHPV vaccine; injection-site AEs were more common with 9vHPV vaccine. Its additional coverage and safety profile support widespread 9vHPV vaccination. WHAT'S KNOWN ON THIS SUBJECT: 9-valent HPV vaccination prevents infection and disease associated with vaccine HPV types in 16-to 26-year-old women. Effi cacy fi ndings were extended to 9-to 15-yearold girls and boys by demonstrating noninferior immunogenicity compared with women.

This study was supported by the Austrian Science Fund (grant P-25187-B13 to J.P. and grant P-28417-B30 to M.K.). There are no competing interests to declare.

An investigational monovalent human papillomavirus (HPV) 16 virus-like particle vaccine has been shown to prevent persistent infection and cervical disease related to HPV 16 and was proof of concept (2002). Designed to prevent the bulk of invasive cervical cancer, quadrivalent (HPV 6/11/16/18) and bivalent (HPV 16/18) vaccines have been available since 2006 and 2007, respectively. They are highly effective in preventing HPV 16/18-related cervical precancer; the quadrivalent version also prevents genital warts related to HPV 6/11. It has been shown that the precursors of vulvar, vaginal and anal cancer related to the vaccine types are effectively prevented. This led to a paradigm shift from a female-only cervical cancer vaccine to a vaccine for the prevention of HPV-related disease and cancer for both sexes. Vaccination before the start of sexual activity is most effective, and consequently most programs target 9- to 12-year-olds. Additionally, recent studies have proven the noninferior immunoresponse of a two-dose schedule in these age cohorts. Gender-neutral vaccination has become more common; it improves coverage and also provides protection to all males. Recently a nine-valent HPV vaccine (HPV 6/11/16/18/31/33/45/52/58) was licensed; it provides high and consistent protection against infections and diseases related to these types, with ∼90% of cervical and other HPV-related cancers and precancers potentially being avoided. Coverage is key. Efforts must be made to provide HPV vaccination in low-resource countries that lack screening programs. In countries with cervical cancer screening, HPV vaccination will greatly affect screening algorithms.