Summary Background A new test ( care HPV; QIAGEN, Gaithersburg, MD, USA) has been developed to detect 14 high-risk types of carcinogenic human papillomavirus (HPV) in about 2·5 h, to screen women in ...developing regions for cervical intraepithelial neoplasia (CIN). We did a cross-sectional study to assess the clinical accuracy of care HPV as a rapid screening test in two county hospitals in rural China. Methods From May 10 to June 15, 2007, the care HPV test was done locally by use of self-obtained vaginal and provider-obtained cervical specimens from a screening population-based set of 2530 women aged 30 to 54 years in Shanxi province, China. All women were assessed by visual inspection with acetic acid (VIA), Digene High-Risk HPV HC2 DNA Test (HC2), liquid-based cytology, and colposcopy with directed biopsy and endocervical curettage as necessary. In 2388 women with complete data, 441 women with negative colposcopy, but unsatisfactory or abnormal cytology or who were positive on HC2 or the new care HPV test, were recalled for a second colposcopy, four-quadrant cervical biopsies, and endocervical curettage. An absence of independence between the tests was not adjusted for and the Bonferroni correction was used for multiple comparisons. Findings Complete data were available for 2388 (94·4%) women. 70 women had CIN2+ (moderate or severe CIN or cancer), of whom 23 had CIN3+. By use of CIN2+ as the reference standard and area-under-the-curve analysis with a two-sided alpha error level of 0·0083, the sensitivities and specificities of the care HPV test for a cut-off ratio cut-point of 0·5 relative light units, were 90·0% (95% CI 83·0–97·0) and 84·2% (82·7–85·7), respectively, on cervical specimens, and 81·4% (72·3–90·5) and 82·4% (80·8–83·9), respectively, on vaginal specimens (areas under the curve not significantly different, p=0·0596), compared with 41·4% (29·9–53·0) and 94·5% (93·6–95·4) for VIA (areas under the curve significantly different, p=0·0001 and p=0·0031, for cervical and vaginal-specimen comparisons for the care HPV test, respectively). The sensitivity and specificity of HC2 for cervical specimens were 97·1% (93·2–100) and 85·6% (84·2–87·1), respectively (areas under the curve not significantly different from the care HPV test on cervical specimens, p=0·0163). Interpretation The care HPV test is promising as a primary screening method for cervical-cancer prevention in low-resource regions. Funding Bill & Melinda Gates Foundation.
Summary 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 30 371 women from 17 cross-sectional, population-based studies in 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 in the overall HPV DNA positivity from 16·3% to 13·9% (p<0·0001), which could result in 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 in 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. Funding Fogarty International Clinical Research Scholars Program (Fogarty International Center, US National Institutes of Health, through the International Clinical Research Fellows Program at Vanderbilt University); Academic Capacity Development Program of the Beijing Municipal Commission of Education; and Cancer Institute and Hospital of the Chinese Academy of Medical Sciences.
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