David Mesher

Impact of knowledge of human papillomavirus positivity on cervical cytology performance in Latin America

Abstract Background Cervical cytology is recommended by the World Health Organization as a triage option in human papillomavirus (HPV)-based cervical cancer screening programs. We assessed the performance of cytology to detect CIN3+ without and with knowledge of HPV positivity. Methods Women were screened with cytology and HPV across ESTAMPA study centers in Latin America. Screen-positives were referred to colposcopy with biopsy and treatment as needed. Cytology was initially interpreted without knowing HPV results. A subset of cytologies from HPV-positive women were reinterpreted at the same laboratories, with knowledge of HPV status, blinded to previous cytology and histological diagnosis. Performance indicators for cytology to detect CIN3+ without and with knowledge of HPV positivity were estimated. Findings A total of 4087 women were included, of which 490 had histologically confirmed CIN3+ (455 CIN3 and 35 cancers). Cytology sensitivity without knowledge of HPV positivity for CIN3+ was 47.2% (95% CI = 42.5 to 51.9), whereas with knowledge of HPV positivity, the sensitivity was higher (58.9%, 95% CI = 54.2 to 63.5; P < .0001). The specificity without knowledge of HPV was 89.4% (95% CI = 88.2 to 90.5), whereas with knowledge of HPV positivity was 78.9% (95% CI = 77.4 to 80.4; P < .0001). Performance estimates varied by study center for cytology without knowing the HPV positivity (range = 32.8%-61.5% for sensitivity; range = 80.7%-98.6% for specificity). Similarly, performance varied with knowledge of HPV positivity (36.1%-93.4% for sensitivity; 39.6%-98.6% for specificity). Conclusion The increase in sensitivity of cytology with HPV knowledge was limited and highly variable, reinforcing the need for alternative triage methods to support cervical cancer elimination goals.

The impact of catch-up bivalent human papillomavirus vaccination on cervical screening outcomes: an observational study from the English HPV primary screening pilot

Abstract Background In England, bivalent vaccination (Cervarix) against high-risk human papillomavirus (HR-HPV) genotypes 16/18 was offered in a population-based catch-up campaign in 2008–2010 to girls aged 14–17 years. These women are now entering the national cervical screening programme. We determined the impact of catch-up bivalent vaccination on their screening outcomes. Methods We studied the overall and genotype-specific screening outcomes in 108,138 women aged 24–25 (offered vaccination) and 26–29 years (not offered vaccination) included in the English HPV screening pilot between 2013 and 2018. Results At 24–25 years, the detection of high-grade cervical intraepithelial neoplasia (CIN2+) associated with HPV16/18 decreased from 3 to 1% (p < 0.001), with estimated vaccine effectiveness of 87% (95% CI: 82–91%). The detection of any CIN2+ halved from 6 to 3% (p < 0.001), with an estimated vaccine effectiveness of 72% (95% CI: 66–77%). The positive predictive value of a colposcopy for CIN2+ decreased for both low-grade (p < 0.001) and high-grade (p = 0.02) abnormalities on triage cytology. The decreases in screen-detected abnormalities at age 26-29 were of a substantially smaller magnitude. Conclusions These data confirm high effectiveness of bivalent HPV vaccination delivered through a population-based catch-up campaign in England. These findings add to the rationale for extending screening intervals for vaccinated cohorts.

The impact of over ten years of HPV vaccination in England: Surveillance of type-specific HPV in young sexually active females

The UK national human papillomavirus (HPV) vaccination programme was introduced in 2008 using the bivalent HPV16/18 vaccine, changing to the quadrivalent HPV6/11/16/18 vaccine from 2012. We provide an analysis of type-specific HPV prevalence in young sexually active females in England to end 2020 (when the first routinely HPV vaccinated females were reaching 25 years of age and entering the National Health Service Cervical Screening Programme), showing the impact of over ten years of high coverage HPV vaccination. Residual vulvovaginal swabs (VVS) were collected from 16 to 24 year old women attending for chlamydia screening between 2010 and 2020, anonymised and tested for type-specific HPV DNA. Trends in vaccine and non-vaccine HPV type prevalence were compared over time and association with vaccination coverage was evaluated within the post-vaccination period. A total of 21,168 eligible VVS specimens were tested for HPV DNA. The prevalence of HPV16/18 in sexually active 16-18 year old females who were offered vaccination aged 12-13 years was <1% in the most recent years tested, compared to over 15% prior to the vaccination programme in 2008. The magnitude of these decreases also suggests reduced transmission is offering some herd protection to unvaccinated females. HPV31/33/45 prevalence also steadily decreased, providing evidence of cross-protection. HPV6/11 prevalence remained stable during the bivalent vaccine period, with more recent declines, as expected due to the use of the quadrivalent vaccine. There has been no substantive increase in the prevalence of other high-risk (HR) HPV types. More than ten years of high coverage HPV vaccination in adolescent females in England has delivered dramatic declines in the prevalence of HPV vaccine-types and closely related HPV types in females in the vaccine eligible age group, and no indication of type replacement. These findings should enable confidence in planning for cervical screening of these females, and in predicting declines in HPV-related cancers.