| Summary: | Background: This study aimed to evaluate three different patterns of cervical cancer screening strategies for detection of cervical diseases. Methods: In total, 10,186 women aged 21–70 years attending cervical screening program were recruited and cotested by human papillomavirus (HPV) assays and cytology. Three-year histological follow-up data was recorded on women with abnormal screening results, and six clinically common screening algorithms were evaluated. Results: Significantly better protection against cervical intraepithelial neoplasia 2 or worse (CIN2+) at three-year follow-up was associated with a negative HPV result than by normal cytology at baseline. HPV screening was more sensitive and less specific than cytology screening. Moreover, HPV screening with HPV16/18 and reflex cytology (atypical squamous cells of undetermined significance [ASCUS] threshold) showed a similar sensitivity (94.6% vs. 98.2%, p = 0.125) and a superior specificity as compared to cotesting reflex HPV16/18 and cytology (ASCUS threshold) for CIN2+ (95.8% vs. 95.1%, p < 0.0001), achieving a colposcopy referral rate of 5.4%, and consuming 4.8 colposcopies and 4.4 cytology tests to find one CIN2+. Conclusions: HPV screening with triage of HPV-positive women by HPV16/18 genotyping and cytology provided a good equilibrium between screening effectiveness, the number of cytology tests required, and referral rates; HPV testing was similar in sensitivity to cotesting and safer than cytology, thus especially suitable for large population-based screening programs.
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