Head-to-head comparison of two human papillomavirus vaccines for efficacy against cervical intraepithelial neoplasia grade 3 and adenocarcinoma -population-based follow-up of two cluster-randomized trials.

Introduction: We report head-to-head comparison of the bivalent and quadrivalent HPV vaccine efficacies against immediate precursors of cervical cancer from 15 years' country-wide cancer registry follow-up of phase III trial cohorts and an age-aligned cohort of unvaccinated women.

Methods: These individually and/or clusterrandomized cohorts of HPV6/11/16/18- and HPV16/18-vaccinated and unvaccinated women were enrolled, respectively, in 2002, 2004, and 2003/2005. The trial cohorts comprised initially 16- to 17-year-old HPV6/11/16/18-vaccinated FUTURE II (NCT00092534) participants (866) and HPV16/18-vaccinated PATRICIA (NCT00122681) and 012 trial (NCT00169494) participants (2,465), and 16,526 initially 16- to 19-year-old unvaccinated controls.

Incidence of Cytomegalovirus Primary and Secondary Infection in Adolescent Girls: Results From a Prospective Study.

Developing a vaccine to prevent congenital cytomegalovirus (CMV) infection and newborn disability requires an understanding of infection incidence. In a prospective cohort study of 363 adolescent girls (NCT01691820), CMV serostatus, primary infection, and secondary infection were determined in blood and urine samples collected at enrollment and every 4 months for 3 years. Baseline CMV seroprevalence was 58%.

Pooled efficacy results of estetrol/drospirenone combined oral contraception phase 3 trials.

Objective: To evaluate overall and subgroup efficacy of an estetrol (E4) 15 mg drospirenone (DRSP) 3 mg oral contraceptive in a 24/4-day regimen.

Study Design: We pooled efficacy outcomes from 2 pivotal phase 3 contraceptive trials with E4/DRSP conducted in the United States/Canada and Europe/Russia. We assessed Pearl Index (PI; pregnancies per 100 participant-years) and 13-cycle life-table pregnancy rates in at-risk cycles (confirmed intercourse and no other contraceptive use) among participants 16 to 35 years.

Association of infection with cervical atypia in adolescent women with short-term or long-term use of oral contraceptives: a longitudinal study in HPV vaccinated women.

Objective: We assessed the relationship between infection, duration of oral contraceptive (OC) use and cervical atypia among young adult Finnish women.

Design: A longitudinal study.

Setting And Participants: Women who were included in this study participated in a community-randomised trial on the effectiveness of human papillomavirus (HPV) vaccination and screening at ages 18.

Human papillomavirus vaccine efficacy against invasive, HPV-positive cancers: population-based follow-up of a cluster-randomised trial.

Background: Human papillomavirus (HPV) vaccination protects against HPV, a necessary risk factor for cervical cancer. We now report results from population-based follow-up of randomised cohorts that vaccination provides HPV-type-specific protection against invasive cancer.

Methods: Individually and/or cluster randomised cohorts of HPV-vaccinated and non-vaccinated women were enrolled in 2002-2005.

Effectiveness of various human papillomavirus vaccination strategies: A community randomized trial in Finland.

Introduction: We conducted a community-randomized trial (NCTBLINDED) in Finland to assess gender-neutral and girls-only vaccination strategies with the AS04-adjuvanted human papillomavirus (HPV)-16/18 (AS04-HPV-16/18)vaccine.

Methods: Girls and boys (12-15 years) were invited. We randomized 33 communities (1:1:1 ratio): Arm A: 90% of randomly selected girls and boys received AS04-HPV-16/18 vaccine and 10% received hepatitis B vaccine (HBV); Arm B: 90% of randomly selected girls received AS04-HPV-16/18 vaccine, 10% of girls received HBV, and all boys received HBV; Arm C: all participants received HBV.

Estetrol-Drospirenone combination oral contraceptive: a clinical study of contraceptive efficacy, bleeding pattern and safety in Europe and Russia.

Objectives: To assess the contraceptive efficacy, bleeding pattern and safety of a combined oral contraceptive containing estetrol (E4) 15 mg and drospirenone (DRSP) 3 mg.

Design: Multicenter, open-label, phase 3 trial.

Setting: Sixty-nine sites in Europe and Russia.

Three Dose Levels of a Maternal Respiratory Syncytial Virus Vaccine Candidate Are Well Tolerated and Immunogenic in a Randomized Trial in Nonpregnant Women.

Background: Respiratory syncytial virus (RSV) causes respiratory tract infections, which may require hospitalization especially in early infancy. Transplacental transfer of RSV antibodies could confer protection to infants in their first months of life.

Methods: In this first-in-human, placebo-controlled study, 502 healthy nonpregnant women were randomized 1:1:1:1 to receive a single dose of unadjuvanted vaccine containing 30/60/120 µg of RSV fusion (F) protein stabilized in the prefusion conformation (RSVPreF3) or placebo.

Comparative pharmacokinetic analysis of levonorgestrel-releasing intrauterine systems and levonorgestrel-containing contraceptives with oral or subdermal administration route.

Objective: To compare systemic exposure to levonorgestrel (LNG) released from commercially available intrauterine systems (IUSs), a subdermal implant, and oral contraceptives.

Methods: An integrated population pharmacokinetic (popPK) analysis of data from over 3400 individuals in ten clinical studies with six different LNG-releasing contraceptives (four long-acting reversible contraceptives [LARCs: LNG-IUS 8, 12, and 20, initially releasing LNG 14, 17.5, and 20 μg/day, a subdermal implant initially releasing LNG 100 μg/day according to label]; progestin-only pill [POP: LNG 30 μg/day]; and combined oral contraceptive [COC] pill [LNG 100 μg/day and ethinylestradiol 20 μg/day]), was conducted to generate a popPK model.

Oestrogen-free oral contraception with a 4 mg drospirenone-only pill: new data and a review of the literature.

The contraceptive pill is an effective and safe method of preventing pregnancy. The progestins used for contraception either are components of a combined hormonal contraceptive (tablets, patches or vaginal rings) or are used alone in progestin-only formulations. Progestin-only contraceptives are available as daily oral preparations, subcutaneous or intramuscular injectables (every 1-3 months), subdermal implants (every 3-5 years) and intrauterine systems (every 3-5 years).

Verbal and Behavioral Expressions of Child Sexuality Among 1-6-Year-Olds as Observed by Daycare Professionals in Finland.

A safe childhood respecting sexual rights forms the foundation of an individual's sexual health. However, the understanding, support, and protection of early sexuality are seldom discussed. Children already express their sexuality verbally and behaviorally in daycare, often requiring a response from staff.

Vaccination With Moderate Coverage Eradicates Oncogenic Human Papillomaviruses If a Gender-Neutral Strategy Is Applied.

Background: Human papillomavirus (HPV) vaccination of girls with very high (>90%) coverage has the potential to eradicate oncogenic HPVs, but such high coverage is hard to achieve. However, the herd effect (HE) depends both on the HPV type and the vaccination strategy.

Methods: We randomized 33 Finnish communities into gender-neutral HPV16/18 vaccination, girls-only HPV16/18 vaccination, and hepatitis B virus vaccination arms.

Multicenter, open-label trial to assess the safety and tolerability of drospirenone 4.0 mg over 6 cycles in female adolescents, with a 7-cycle extension phase.

Objective: To assess the safety, tolerability and bleeding patterns of drospirenone 4.0 mg.

Study Design: A multicenter, open-label, safety trial in sexually-active adolescents aged 12-17 years for six 28-day treatment cycles (Core Phase) and an optional 7-13 cycle extension with administration of drospirenone 4.

Safety of the AS04-adjuvanted human papillomavirus (HPV)-16/18 vaccine in adolescents aged 12-15 years: end-of-study results from a community-randomized study up to 6.5 years.

This manuscript discloses end-of-study safety data of a community-randomized controlled trial in Finland (NCT00534638), assessing the effectiveness of two vaccination strategies (gender-neutral versus females only) using the AS04-adjuvanted human papillomavirus (HPV)-16/18 (AS04-HPV-16/18) vaccine. The total vaccination cohort included 32,175 adolescents aged 12-15 y at vaccination of whom 14,837 received the AS04-HPV-16/18 vaccine and 17,338 received the hepatitis-B virus vaccine (control). Spontaneous reporting of serious adverse events (SAEs) combined with surveillance using nation-wide health registries showed an acceptable safety profile of the AS04-HPV-16/18 vaccine.

Baseline findings and safety of infrequent vs. frequent screening of human papillomavirus vaccinated women.

Less frequent cervical cancer screening in human papillomavirus (HPV) vaccinated birth cohorts could produce considerable savings without increasing cervical cancer incidence and loss of life-years. We report here the baseline findings and interim results of safety and accuracy of infrequent screening among HPV16/18 vaccinated females. The entire 1992-1994 birth-cohorts (30,139 females) were invited to a community-randomized HPV16/18-vaccination trial.

Effectiveness of the AS04-adjuvanted HPV-16/18 vaccine in reducing oropharyngeal HPV infections in young females-Results from a community-randomized trial.

We studied effectiveness of the AS04-adjuvanted HPV-16/18 (AS04-HPV-16/18) vaccine against human papillomavirus (HPV) oropharyngeal infections associated with the increase of head/neck cancers in western countries. All 38,631 resident adolescents from 1994 to 1995 birth cohorts of 33 Finnish communities were invited in this community-randomized trial (NCT00534638). During 2008-2009, 11,275 girls and 6,129 boys were enrolled in three arms of 11 communities each.

International Perspectives: IUDs and Adolescents.

Unplanned or unwanted pregnancy among adolescents is a worldwide public health issue. In many countries unmarried young women are denied contraceptive services. Long-acting reversible contraceptive methods such as the intrauterine devices (IUDs) have been shown to be more effective than short-acting such as the pill, and safe also for adolescents.

Is the risk of cervical atypia associated with the interval between menarche and the start of sexual activity? A population-based cohort study.

Objective: We investigated whether the risk of cervical atypia is associated with a short interval between the age at first sexual intercourse (FSI) or age at the start of oral contraceptive (OC) use and menarche.

Design: A population-based cohort study.

Setting: Finnish women in the age range of 16-17 years old were enrolled in the PATRICIA trial of human papillomavirus (HPV) 16/18 vaccine efficacy.

Efficacy of the 1-year (13-cycle) segesterone acetate and ethinylestradiol contraceptive vaginal system: results of two multicentre, open-label, single-arm, phase 3 trials.

Background: A ring-shaped, contraceptive vaginal system designed to last 1 year (13 cycles) delivers an average of 0·15 mg segesterone acetate and 0·013 mg ethinylestradiol per day. We evaluated the efficacy of this contraceptive vaginal system and return to menses or pregnancy after use.

Methods: In two identically designed, multicentre, open-label, single-arm, phase 3 trials (one at 15 US academic and community sites and one at 12 US and international academic and community sites), participants followed a 21-days-in, 7-days-out segesterone acetate and ethinylestradiol contraceptive vaginal system schedule for up to 13 cycles.

Gender-neutral vaccination provides improved control of human papillomavirus types 18/31/33/35 through herd immunity: Results of a community randomized trial (III).

With optimal strategy, human papillomavirus (HPV) vaccines have the potential to control HPV. We have assessed vaccine efficacy (VE), herd effect (HE) of HPV vaccination and overall protective effectiveness (PE) against high-risk HPV infections by HPV type and vaccination strategy in a community-randomized trial using the bivalent HPV16/18 vaccine. We randomized 33 communities to gender-neutral HPV vaccination (Arm A), HPV vaccination of girls and hepatitis B-virus (HBV) vaccination of boys (Arm B) and gender-neutral HBV vaccination (Arm C).

The risk of cervical atypia in oral contraceptive users.

Background: The interactions of oral contraceptive (OC) use, risk of human papillomavirus (HPV) infection and associated cellular atypia are complex. We investigated the association between history of OC-use, and cytological or histopathological abnormalities in a cohort of non-HPV vaccinated originally 16-17-year-old women participating the PATRICIA trial for 4 years.

Methods: The total number of hepatitis A-virus (control) vaccine recipients participating in the clinical PATRICIA trial in Finland was 2399.

Evaluation of HPV type-replacement in unvaccinated and vaccinated adolescent females-Post-hoc analysis of a community-randomized clinical trial (II).

Efficacy of human papillomavirus (HPV) vaccines promises to control HPV infections. However, HPV vaccination programs may lay bare an ecological niche for non-vaccine HPV types. We evaluated type-replacement by HPV type and vaccination strategy in a community-randomized trial executed in HPV vaccination naïve population.