Human papillomavirus testing alone was more sensitive than conventional cytology for detecting cervical intraepithelial neoplasia, and adding liquid-based cytology to HPV testing only increased the rate of false positives, according to a phase I report from a two-phase randomized controlled trial.
Dr. Guglielmo Ronco of the Centro per la Prevenzione Oncologica, Turin, Italy, and his colleagues from the New Technologies for Cervical Cancer Working Group enrolled more than 33,000 women from nine Italian cancer-screening programs. The primary end point of the analysis was cervical intraepithelial neoplasia grade 2 (CIN2) or higher (as confirmed by histology) or cervical cancer found via the screening test.
One group (16,658 women) was screened via conventional cytology; the experimental group (16,706) was screened by using the ThinPrep liquid-based cytology system (Cytyc Corp., Boxborough, Mass.) and tested for HPV with the Hybrid Capture 2 assay (Digene Corp., Gaithersburg, Md.). Mean patient age was 45 years. Exclusion criteria were pregnancy, prior hysterectomy, or CIN testing within the last 5 years. (J. Natl. Cancer Inst. 2006;98:765–74).
Referral to colposcopy was triggered by a finding of atypical squamous cells of undetermined significance (ASCUS) in the conventional arm and by either findings of ASCUS or a positive (at least 1 pg/mL) HPV test in the experimental arm.
CIN2 or a more severe histology was found in 75 of the women in the experimental arm, 54 of whom had ASCUS or more severe cytology and 73 of whom tested positive for HPV. Among women in the conventional arm, there were 51 women with CIN2 histology or worse.
When compared with the conventional cytology arm, the experimental screening group had higher relative sensitivity (1.47) for detecting CIN2 or greater but the decrease in positive predictive value (11.4% vs. 4.5%) was substantial. ASCUS was the cutoff for colposcopy.
By contrast, HPV testing alone, with 1- and 2-pg/mL cutoffs, increased sensitivity over conventional cytology by 43% and 41%, respectively.
In addition, HPV testing alone, again with 1- and 2-pg/mL cutoffs, avoided the loss of positive predictive value seen when liquid-based cytology was added, 6.6% and 8.5%, respectively.
“Our data strongly suggest that supplementing HPV testing with cytology provides little advantage and mainly increases costs and anxiety,” the authors concluded. They added that the absence of any high-grade lesions among 845 HPV-negative women with ASCUS cytology “strongly supports the use of HPV in triaging ASCUS when cytology is performed first, as previously reported.”