A two-round cervical cancer screening strategy based on testing for human papillomavirus DNA may detect significantly more invasive cancers than one based on cytology.
However, the benefit could come at the expense of overtreatment, especially for younger women, Dr. Guglielmo Ronco and his colleagues reported (Lancet Onc. 2010: DOI:10.1016/S1470-2045(09)70360-2). “For young women … the detection of cervical intraepithelial neoplasia was much higher … at round one, but only slightly lower at round two, suggesting that a large number of regressive CIN2 lesions were identified and treated,” wrote Dr. Ronco of the Center for Cancer Prevention, Turin, Italy, and his co-authors. “Overtreatment of regressive lesions is a problem because excisional treatment of cervical lesions is associated with increased risk of pregnancy-related morbidity.”
The New Technologies for Cervical Cancer (NTCC) screening study randomized 94,000 women to one of two two-round screening programs for cervical cancer. One program was based on cytology alone and the other on HPV testing plus cytology. Women who screened positive for HPV DNA were treated according to their age. Those aged 35–60 years were referred to colposcopy, while those aged 25–34 years were referred to colposcopy only if after a year the test remained positive, or if cytology was atypical squamous cells of undetermined significance (ASCUS) or more severe.
During phase two, women were referred for colposcopy if the HPV test was positive. The primary end point was the number of women with confirmed pre-invasive and invasive cervical cancers.
The subjects' median age at recruitment was 41 years. The median duration of follow-up was 3.5 years.
Both HPV and cytology detected a similar number of invasive cancers during the first round of screening (seven and nine). However, during the second round, no additional cancers were found in the HPV group, while nine cancers were found in the cytology group. Five (55%) of these were squamous cell carcinomas (one stage T1A and four stage T1B) and four (44%) were adenocarcinomas (two stage T1A, one stage T1B, and one TX). This represented a significant increase over the percentage of cervical cancers identified as adenocarcinomas by Italian cancer registries in 2005 (12%), the investigators noted.
Women aged 35–60 years reaped most of the benefit. In the first round, HPV screening detected six invasive cancers and cytology detected eight. In the second round, there were no additional cancers detected in the HPV group, and seven more identified in the cytology group.
For these women, HPV testing detected significantly more CIN2 lesions than cytology (108 vs. 54) during round 1, but significantly fewer during round 2 (8 vs. 15). For CIN3 or adenocarcinoma in situ, HPV testing detected significantly more in round 1 (98 vs. 47) and fewer in round 2 (8 vs. 17). For women aged 25–34 years, HPV testing identified 4.5 times more CIN2 lesions than did cytology testing (126 vs. 27) in round 1. In round 2, HPV testing detected significantly fewer CIN2 lesions than cytology (8 vs. 15). This suggests that the first round of screening identified many lesions that might not have needed treatment.
Disclosures: The study was funded by the European Union and the Italian government. Dr. Ronco disclosed that he has been an adviser to Gen-Probe, which is developing an HPV DNA assay.