Pooled analysis of a self-sampling HPV DNA Test as a cervical cancer primary screening method

Abstract

Background: Worldwide, one-seventh of cervical cancers occur in China, which lacks a national screening program. By evaluating the diagnostic accuracy of self-collected cervicovaginal specimens tested for human papillomavirus (HPV) DNA (Self-HPV testing) in China, we sought to determine whether Self-HPV testing may serve as a primary cervical cancer screening method in low-resource settings.

Methods: We compiled individual patient data from five population-based cervical cancer-screening studies in China. Participants (n = 13 140) received Self-HPV testing, physician-collected cervical specimens for HPV testing (Physician-HPV testing), liquid-based cytology (LBC), and visual inspection with acetic acid (VIA). Screen-positive women underwent colposcopy and confirmatory biopsy. We analyzed the accuracies of pooled Self-HPV testing, Physician-HPV testing, VIA, and LBC to detect biopsy-confirmed cervical intraepithelial neoplasia grade 2 or more severe (CIN2+) and CIN3+. All statistical tests were two-sided.

Results: Of 13 004 women included in the analysis, 507 (3.9%) were diagnosed as CIN2+, 273 (2.1%) as CIN3+, and 37 (0.3%) with cervical cancer. Self-HPV testing had 86.2% sensitivity and 80.7% specificity for detecting CIN2+ and 86.1% sensitivity and 79.5% specificity for detecting CIN3+. VIA had statistically significantly lower sensitivity for detecting CIN2+ (50.3%) and CIN3+ (55.7%) and higher specificity for detecting CIN2+ (87.4%) and CIN3+ (86.9%) (all P values < .001) than Self-HPV testing, LBC had lower sensitivity for detecting CIN2+ (80.7%, P = .015), similar sensitivity for detecting CIN3+ (89.0%, P = .341), and higher specificity for detecting CIN2+ (94.0%, P < .001) and CIN3+ (92.8%, P < .001) than Self-HPV testing. Physician-HPV testing was more sensitive for detecting CIN2+ (97.0%) and CIN3+ (97.8%) but similarly specific for detecting CIN2+ (82.7%) and CIN3+ (81.3%) (all P values <.001) than Self-HPV testing.

Conclusions: The sensitivity of Self-HPV testing compared favorably with that of LBC and was superior to the sensitivity of VIA. Self-HPV testing may complement current screening programs by increasing population coverage in settings that do not have easy access to comprehensive cytology-based screening.

Figure 1

Flow chart of inclusion and exclusion criteria of the study sample. ASC-US = atypical squamous cell of undetermined significance; LBC = liquid-based cytology; LSIL+ = low-grade squamous intraepithelial lesion or more severe; HPV = human papillomavirus; Physician-HPV, physician-collected cervical specimens for HPV testing; Self-HPV = self-collected cervicovaginal specimens tested by HPV DNA testing; VIA = visual inspection with acetic acid.

Figure 2

Forest plots of pooled and individual study sensitivities and specificities of self-collected cervicovaginal specimens tested by HPV DNA testing (Self-HPV) for the detection of CIN2+ (A) and CIN3+ (B) (HPV DNA positivity: RLU/CO ≥ 1 pg/mL). The point estimate of each study was represented by a square, whose size corresponded to the weight of the study in the pooled analysis. A horizontal line represents the 95% confidence interval. The overall estimate was presented at the bottom of the forest plots, represented as a diamond. Two vertical lines around the diamond represent the confidence interval of the overall estimate. CI = confidence interval; CIN2+ = cervical intraepithelial neoplasia grade 2 or more severe; CIN3+ = cervical intraepithelial neoplasia grade 3 or more severe; HPV = human papillomavirus; RLU/CO = relative light units per cutoff; SPOCCS = Shanxi Province Cervical Cancer Screening Study.

Figure 3

ROC curves of self-collected cervicovaginal specimens tested by HPV DNA testing (Self-HPV) for the detection of CIN2+ and CIN3+. Solid lines represent detection of CIN2+; dotted lines represent detection of CIN3+. CIN2+ = cervical intraepithelial neoplasia grade 2 or more severe; CIN3+ = cervical intraepithelial neoplasia grade 3 or more severe; HPV = human papillomavirus; ROC = receiver operating characteristic.