Relative Performance of HPV and Cytology Components of Cotesting in Cervical Screening

Abstract

Background: The main goal of cervical screening programs is to detect and treat precancer before cancer develops. Human papillomavirus (HPV) testing is more sensitive than cytology for detecting precancer. However, reports of rare HPV-negative, cytology-positive cancers are motivating continued use of both tests (cotesting) despite increased testing costs.

Methods: We quantified the detection of cervical precancer and cancer by cotesting compared with HPV testing alone at Kaiser Permanente Northern California (KPNC), where 1 208 710 women age 30 years and older have undergone triennial cervical cotesting since 2003. Screening histories preceding cervical cancers (n = 623) and precancers (n = 5369) were examined to assess the relative contribution of the cytology and HPV test components in identifying cases. The performances of HPV testing and cytology were compared using contingency table methods, general estimating equation models, and nonparametric statistics; all statistical tests were two-sided.

Results: HPV testing identified more women subsequently diagnosed with cancer (P < .001) and precancer (P < .001) than cytology. HPV testing was statistically significantly more likely to be positive for cancer at any time point (P < .001), except within 12 months (P = .10). HPV-negative/cytology-positive results preceded only small fractions of cases of precancer (3.5%) and cancer (5.9%); these cancers were more likely to be regional or distant stage with squamous histopathology than other cases. Given the rarity of cancers among screened women, the contribution of cytology to screening translated to earlier detection of at most five cases per million women per year. Two-thirds (67.9%) of women found to have cancer during 10 years of follow-up at KPNC were detected by the first cotest performed.

Conclusions: The added sensitivity of cotesting vs HPV alone for detection of treatable cancer affected extremely few women.

Figure 1.

Distribution of cotesting results prior to cervical precancer and cancer diagnoses by time period. Shown are all cervical cancers, squamous cell carcinomas (SCC), and adenocarcinomas (ADC) and all precancers (cervical intraepithelial neoplasia grade 3 [CIN3] and adenocarcinoma in situ [AIS]), CIN3, and AIS. From top to bottom the order of the test results is as follows: HPV and cytology negative (HPV−/Cyto−), HPV negative and cytology positive (HPV−/Cyto+), HPV positive and cytology negative (HPV+/Cyto−), and HPV and cytology positive (HPV+/Cyto+).