Species-level characterization of the cervicovaginal microbiota and its role in human papillomavirus-associated cervical carcinogenesis.

The cervicovaginal microbiome may contribute to human papillomavirus (HPV)-associated cervical carcinogenesis, but studies have been limited by low-resolution analysis methods. Using a high-resolution bioinformatics pipeline, we evaluated the relationship of the cervicovaginal microbiome with HPV and cervical intraepithelial neoplasia (CIN). The cervicovaginal microbiome of 186 women was characterized by sequencing 16S rRNA regions (V3-V4 and V5-V6) and annotated with the high-resolution ANCHOR pipeline. Samples were genotyped for HPV using the Roche-Cobas 4800 assay. We fitted logistic regression models using stepwise forward selection to select species (presence/absence) as correlates of CIN1+ and constructed a linear microbiome-based score using the regression coefficients. An HPV-based score was calculated from a separate logistic regression model to detect CIN1+ . Receiver operating characteristic curve analyses were performed; the area under the curve (AUC) and 95% confidence intervals (CI) were compared between scores. Overall, 66.7% of participants were HPV-positive. 77 unique species were identified: 8 using V3-V4, 48 using V5-V6, and 21 shared. Twelve species were retained via stepwise selection. The AUCs for the microbiome-, and HPV-based scores were 0.7656 (95% CI 0.6885-0.8426), and 0.7529 (95% CI 0.6855-0.8204), respectively. Bacterial species may be involved in cervical carcinogenesis as the microbiome- and HPV-based scores performed similarly for CIN1+ detection.

Scientific approaches toward improving cervical cancer elimination strategies.

At the 2023 EUROGIN workshop scientific basis for strategies to accelerate the elimination of cervical cancer and its causative agent, human papillomavirus (HPV) were reviewed. Although some countries have reached key performance indicators toward elimination (>90% of girls HPV vaccinated and >70% of women HPV screened), most are yet to reach these targets, implying a need for improved strategies. Gender-neutral vaccination, even with moderate vaccination coverage was highlighted as a strategy to achieve elimination more rapidly. It is more resilient against major disturbances in vaccination delivery, such as what happened during the coronavirus pandemic. Further, an analysis of ethical/legal issues indicated that female-restricted vaccination is problematic. Extended catch-up of vaccination with concomitant screening, and outreach to vulnerable groups were highlighted. Although birth cohorts with high coverage of HPV vaccination at school are protected against HPV, and HPVs have a very low reproductive rate in women above age 35, adult women below age 30 have inadequate direct protection. In addition to herd protection from gender-neutral vaccination, this group can be protected by offering concomitant catch-up HPV vaccination and HPV screening. Furthermore, hepatitis B vaccination experiences indicate that elimination cannot be achieved without prioritizing vulnerable/migrant populations. The long-lasting durability of vaccination-induced antibody responses suggests prolonged protection with HPV vaccines when adequately administrated. Finally, cost-effectiveness modelling suggests that high-coverage HPV vaccination in multiple population segments will be resource-saving due to reduced need for screening. In summary, the workshop found that strategically optimal deployment of vaccination will accelerate elimination of HPV and cervical cancer.

A Review of Ethical and Legal Aspects of Gender-Neutral Human Papillomavirus Vaccination.

While launching a campaign to eliminate cervical cancer, the World Health Organization called to halt human papillomavirus (HPV) gender-neutral vaccination (GNV) because of limited vaccine supply, raising ethical and legal questions about female-only vaccination versus GNV. We identified ethical and legal aspects of HPV GNV by searching MEDLINE for records up to February 19, 2021. We also provided an overview of HPV vaccines, the evolution of HPV vaccine recommendations in North America, and a timeline of male HPV vaccination introduction by searching PubMed, Google, and government websites. Four HPV vaccines are available: Cervarix, Gardasil, Gardasil9, and Cecolin. Vaccine recommendations in North America evolved from female only to eventually include males. Following the FDA's approval of the first HPV vaccine for males (2009), 35 countries began vaccinating males (2011-2020). On the basis of 59 eligible records out of 652, we identified the following constructs: lower male awareness of HPV and vaccination (n = 13), limited economic resources (n = 5), shared social responsibility (n = 18), unprotected groups from female-only HPV vaccination (n = 10), limited screening for HPV-associated noncervical cancers (n = 6), consideration of ethical principles (n = 17), and HPV vaccine mandates (n = 5). Ethical and legal aspects must be considered when recommending vaccination for females only or GNV.