Performance of high-risk human papillomavirus DNA testing as a primary screen for cervical cancer: a pooled analysis of individual patient data from 17 population-based studies from China

Background Controversy remains over whether high risk human papillomavirus (HPV) DNA testing should be used as a primary screen for cervical cancer The aims of our study were to assess whether HPV DNA testing could be applied to cervical cancer screening programmes in China as well as other similar developing countries Methods We did a pooled analysis of population based cervical cancer screening studies done in mainland China from 1999 to 2008 with concurrent HPV DNA testing (Hybrid Capture 2 assay Qiagen, Gaithersburg MD USA) liquid based cytology (LBC), and visual inspection with acetic acid (VIA) Eligible women were sexually active not pregnant had an Intact uterus and had no history of cervical intraepithelial neoplasia (CIN) cervical cancer or pelvic irradiation All women positive for any test were referred for colposcopy and biopsy Cervical lesions were diagnosed by directed or random biopsy We assessed the diagnostic accuracy of HPV DNA testing for the detection of CIN grade 3 or greater Findings 30371 women from 17 cross sectional population based studies m various parts of China were screened 1523 women were subsequently excluded because of inadequate HPV DNA specimens or they did not have a biopsy taken which included women with atypical squamous cells of undetermined significance, low grade squamous intraepithelial lesion or worse positive HPV negative cytology and missing or positive colposcopy results and unsatisfactory cytology results HPV DNA testing had a higher sensitivity of 97 5% (95% CI 95 7-98 7) for detection of CIN grade 3 or worse and a lower specificity of 85 1% (82 3-87 9) compared with cytology (sensitivity 87 9% [95% CI 84 7-90 7], specificity 94 7% [93 5-96 0]) and VIA (54 6% [48 0-61 2] 89 9% [86 8-93 0]) Sensitivity did not vary by study or age (<35 years 35-49 years >= 50 years) however specificity did vary with age (p<0 0001) and was highest in women younger than 35 years (89 4% 95% CI 86 1-91 5) An increase in the positive cutoff point from the manufacturer recommended 1 pg/mL to 2 pg/mL led to a decrease m the overall HPV DNA positivity from 16 3% to 13 9% (p<0 0001) which could result m a decrease in referral rates although sensitivity was slightly lower (97 5% to 95 2%) An increase in the cutoff point to 10 pg/mL m women younger than 35 years maintained a high sensitivity 97 7% (95% CI 87 7-99 9) and increased specificity to 93 5% (95% CI 91 9-94 6) Interpretation HPV DNA testing is highly sensitive and moderately specific for CIN grade 3 or worse with consistent results across study sites and age groups-including women younger than 35 years A rise in the cutoff point might be beneficial for future screening programmes in China especially when screening women younger than 35 years