Background More than ten years have elapsed since human papillomavirus (HPV) vaccination was implemented. We performed a systematic review and meta-analysis of the population-level impact of female-only HPV vaccination on HPV infections, anogenital wart diagnoses (AGW) and cervical intraepithelial neoplasia grade 2+ (CIN2+) to summarise the most recent evidence about the effectiveness of HPV vaccines in real-world settings and to quantify the impact of multiple age-cohort vaccination. Methods We updated our prior review (01/01/2007-28/02/2014), by searching Medline and Embase (01/02/2014-11/10/2018) for studies that examined changes, between pre-and post-vaccination periods, in HPV infections, AGW, or CIN2+. We stratified all analyses by sex, age, and years since HPV vaccination introduction. We used random-effects models to estimate pooled relative risks and performed subgroup analysis to identify the main sources of heterogeneity. Findings We identified 65 eligible articles conducted in 14 high-income countries. After 5-8 years of vaccination, HPV-16/18, AGW, and CIN2+ decreased significantly by about 80%, 70%, and 50% among girls aged 15-19 years and by 65%, 55%, and 30% among women aged 20-24 years. Significant cross-protection and herd effects were also observed. HPV-31/33/45 decreased significantly by 50% among girls aged 15-19 years and AGW decreased significantly by 30-50% among boys/men aged 15-24 years. After 5-8 years of vaccination, countries with multi-cohort vaccination and high coverage (≥50%) had greater reductions in AGW, 44 and 85 percentage points among girls and boys aged 15-19 years, respectively, than countries with single-cohort vaccination and/or low vaccination coverage. Interpretation Our meta-analysis, including data from >60 million individuals from 14 high-income countries, shows a substantial impact of female-only HPV vaccination programs on AGW among girls/women and boys/men, and HPV infections and CIN2+ among girls/women. In addition, programs with multi-cohort vaccination and high vaccination coverage lead to greater and faster direct impact and herd effects. CONTRIBUTIONS MD, MB, and MCB conceived the study. MD, EB and NP did the literature search and performed the analysis. MB and MCB participated in the analysis. MD and MB co-drafted the first version of the article.

Summary Background Human papillomavirus (HPV) vaccination programmes were first implemented in several countries worldwide in 2007. We did a systematic review and meta-analysis to assess the population-level consequences and herd effects after female HPV vaccination programmes, to verify whether or not the high efficacy reported in randomised controlled clinical trials are materialising in real-world situations. Methods We searched the Medline and Embase databases (between Jan 1, 2007 and Feb 28, 2014) and conference abstracts for time-trend studies that analysed changes, between the pre-vaccination and post-vaccination periods, in the incidence or prevalence of at least one HPV-related endpoint: HPV infection, anogenital warts, and high-grade cervical lesions. We used random-effects models to derive pooled relative risk (RR) estimates. We stratified all analyses by age and sex. We did subgroup analyses by comparing studies according to vaccine type, vaccination coverage, and years since implementation of the vaccination programme. We assessed heterogeneity across studies using I2 and χ2 statistics and we did trends analysis to examine the dose–response association between HPV vaccination coverage and each study effect measure. Findings We identified 20 eligible studies, which were all undertaken in nine high-income countries and represent more than 140 million person-years of follow-up. In countries with female vaccination coverage of at least 50%, HPV type 16 and 18 infections decreased significantly between the pre-vaccination and post-vaccination periods by 68% (RR 0·32, 95% CI 0·19–0·52) and anogenital warts decreased significantly by 61% (0·39, 0·22–0·71) in girls 13–19 years of age. Significant reductions were also recorded in HPV types 31, 33, and 45 in this age group of girls (RR 0·72, 95% CI 0·54–0·96), which suggests cross-protection. Additionally, significant reductions in anogenital warts were also reported in boys younger than 20 years of age (0·66 [95% CI 0·47–0·91]) and in women 20–39 years of age (0·68 [95% CI 0·51–0·89]), which suggests herd effects. In countries with female vaccination coverage lower than 50%, significant reductions in HPV types 16 and 18 infection (RR 0·50, 95% CI 0·34–0·74]) and in anogenital warts (0·86 [95% CI 0·79–0·94]) occurred in girls younger than 20 years of age, with no indication of cross-protection or herd effects. Interpretation Our results are promising for the long-term population-level effects of HPV vaccination programmes. However, continued monitoring is essential to identify any signals of potential waning efficacy or type-replacement. Funding The Canadian Institutes of Health Research.

The high prevalence of TNTs among younger women and particularly younger AA women, along with unique protein expression patterns and poorer survival, suggests varying gene-environment etiologies with respect to age and race/ethnicity and a need for effective therapies.

Objective Predictors of intrinsic breast cancer subtypes, including the triple-negative (TN) subtype, are largely unknown. We evaluated whether anthropometrics, demographics, and reproductive history were associated with distinct breast cancer subtypes. Methods Invasive breast tumors from a population-based case–control study of 476 (116 black and 360 white) Atlanta women aged 20–54, diagnosed between 1990 and 1992, were centrally reviewed and immunohistochemically analyzed for estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2); then grouped [TN (ER−PR−HER2−); ER−PR−HER2+; ER/PR+HER2+; ER/PR+HER2− (case-only reference group)]. Data were from interviews and anthropometric measurements; adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression, including both case-only and case-control comparisons. Results From the case-only analyses and compared with the ER/PR+HER2− subtype, women with TN tumors were more likely to be obese than normal/underweight [OR = 1.89 (95% CI = 1.22, 2.92)]. Regardless of HER2 status, ER−PR− tumors were associated with black race, young age at first birth, having a recent birth, and being overweight. Conclusions Distinct breast cancer subtypes have unique sociodemographic, anthropometric and reproductive characteristics and possibly different pathways for development.