Mette Hartmann Nonboe

Human papillomavirus prevalence in first, second and third cervical cell samples from women HPV-vaccinated as girls, Denmark, 2017 to 2024: data from the Trial23 cohort study

BACKGROUND Danish women vaccinated with the 4-valent human papillomavirus (HPV) vaccine (HPV types: 6/11/16/18) at age 14 in 2008 reached screening age in 2017, allowing assessment of long-term effects on prevalence, persistence and incidence of HPV infections. AIM To examine the HPV status of cervical samples over time among women vaccinated as girls. METHODS Between February 2017 and February 2024, residual material from cytology-analysed samples collected through the ‘Trial23’ study, part of the national screening programme, was tested for HPV16/18 and non-vaccine high-risk (HR) HPV types. Prevalence in first, second and third samples, and persistence and incidence between samples were calculated. RESULTS Over 7 years, 8,659 women provided at least one sample, 5,835 at least two and 2,461 at least three. In 7,800 vaccinated women, HPV16/18 prevalence was 0.4% (95% confidence interval (CI): 0.2–0.5), 0.3% (95% CI: 0.1–0.4) and 0.2% (95% CI: 0.0–0.4) in three consecutive samples. Prevalence of non-vaccine HR HPV was 32% (95% CI: 31–33), 28% (95% CI: 27–29) and 31% (95% CI: 29–33). Persistence of HPV16/18 and non-vaccine HPV among vaccinated women was 40% and 53%. In adjusted analyses comparing vaccinated vs unvaccinated women, incidence was significantly lower for HPV16/18 (adjusted relative risk (aRR) < 0.10) while incidence of non-vaccine HR HPV types was higher (aRR: 1.66; 95% CI: 1.12–2.45). No significant difference was observed for persistence. CONCLUSION Our study provides real-world evidence of stable protection against HPV16/18 infections in women vaccinated as girls. Less intensive screening seems reasonable until women vaccinated with the 9-valent vaccine reach screening age, when screening should be reconsidered.

Screening outcome of HPV-vaccinated women: Data from the Danish Trial23 cohort study

Background Danish women—who were HPV-vaccinated as girls—are now reaching an age where they are invited to cervical cancer screening. Because of their expected lower cervical cancer risk, we must reassess our screening strategies. We analyzed Danish HPV-vaccinated women’s outcomes after the first screening test at age 23. Methods and findings Our study was embedded in Danish routine cytology-based screening. We conducted an observational study and included women born in 1994, offered the 4-valent HPV vaccine at age 14, and subsequently invited to screening at age 23. Cervical cytology was used for diagnostics and clinical management. Residual material was HPV tested with Cobas® 4800/6800. The most severe histology diagnosis within 795 days of screening was found through linkage with the Danish National Pathology Register. We calculated the number of women undergoing follow-up (repeated testing and/or colposcopy) per detected cervical intraepithelial neoplasia (CIN2+). A total of 6021 women were screened; 92% were HPV-vaccinated; 12% had abnormal cytology; 35% were high-risk HPV-positive, including 0.9% HPV16/18 positive, and 20% had follow-up. In women that were cytology-abnormal and HPV-positive (Cyt+/HPV+), 610 (98.5%) had been followed up, and 138 CIN2+ cases were diagnosed, resulting in 4.4 (95% CI 3.9–5.2) women undergoing follow-up per detected CIN2+. In contrast to recommendations, 182 (12.2%) cytology-normal and HPV-positive (Cyt-/HPV+) women were followed up within 795 days, and 8 CIN2+ cases were found, resulting in 22.8 (95% CI 13.3–59.3) women undergoing follow-up per detected CIN2+. Conclusion Overall, HPV prevalence was high in HPV-vaccinated women, but HPV16/18 had largely disappeared. In the large group of cytology-normal and HPV-positive women, 23 had been followed up per detected CIN2+ case. Our data indicated that primary HPV screening of young HPV-vaccinated women would require very effective triage methods to avoid an excessive follow-up burden. Trial registration Trial registration number: NCT0304955.