Age-specific effectiveness of primary human papillomavirus screening versus cytology in a cervical cancer screening program: a nationwide cross-sectional study

Abstract

Background: Primary human papillomavirus (HPV) screening is recommended for the detection of cervical intraepithelial neoplasia (CIN) in the general population; however, the triage for HPV-positive women remains a challenge. This study aimed to evaluate the age-specific effectiveness of primary HPV screening versus primary cytology screening for identifying optimal strategies for women of different ages. Methods: The dataset of the prevalence round screening was derived from the National Cervical Cancer Screening Program in China. Primary cervical screening protocols included cytology only, HPV testing with cytology triage, and HPV testing with HPV-16/18 genotyping plus cytology triage. The primary outcomes were age-specific detection rate, colposcopy referral rate and positive predictive value (PPV) for CIN2+. Multivariate Poisson regression was used to evaluate the relative effectiveness of HPV testing and cytology according to age groups. The I2 statistic with a random-effect model was used to test the heterogeneity in relative effectiveness of HPV testing versus cytology between age groups. Results: This study included 1,160,981 women. HPV testing with HPV-16/18 genotyping plus cytology triage significantly increased the CIN2+ detection by 36% (rate ratio [RR]: 1.36, 95% confidential interval [CI] 1.21–1.54) for women aged 35-44 years and by 34% (RR: 1.34, 95% CI 1.20-1.51) for women aged 45-54 years compared with cytology only. HPV testing with cytology triage had similar CIN2+ detection rate compared with cytology only. The PPVs were substantially increased for both HPV testing groups. Among women aged 55-64 years old, HPV testing with HPV-16/18 genotyping plus cytology triage increased the colposcopy referral rate by 19% (RR 1.19, 95% CI 1.10-1.29) compared with cytology only, but did not increase the CIN2+ detection (1.09, 0.91–1.30). The effectiveness of HPV testing with cytology triage did not change in older women. The between-age-group heterogeneity in the effectiveness was statistically significant for HPV testing with HPV-16/18 genotyping plus cytology triage versus cytology only. Conclusions: Our results suggested that the effectiveness of primary HPV screening with different triage strategies differed among age groups. HPV testing with HPV-16/18 genotyping plus cytology triage could be used for women aged 35-54 years to detect more lesions, and HPV testing with cytology triage could balance the CIN2+ detection and the number of colposcopies for women aged 55-64 years. Longitudinal data including both prevalence and incidence screening rounds are warranted to assess age-specific triage strategies.