Human Papillomavirus DNA versus Papanicolaou Screening Tests for Cervical Cancer

To the Editor: The outcome measures appear to have been chosen post hoc by Mayrand et al. (Oct. 18 issue)1 in their screening trial comparing human papillomavirus (HPV) testing with Papanicolaou (Pap) testing.1,2 The “conservative” outcome definition excludes biopsy-confirmed lesions identified at colposcopy but not verified on final excision or on biopsy immediately before ablation. Such lesions are included in the “liberal” definition, along with lesions identified by random biopsy and endocervical curettage. With the conservative definition, HPV testing is clearly superior, whereas with the liberal definition, neither strategy is clearly superior. Lesions included in the liberal definition may have no potential to progess, but it is unusual to extend this rationale to lesions seen at colposcopy. The authors suggest that these visible lesions may have been squamous metaplasia histologically misinterpreted as high-grade cervical intraepithelial neoplasia (grade 2 or higher), but this hypothesis was never confirmed by pathological re-review of the targeted biopsy specimens. We propose an alternative outcome measure: the presence of histologically verified, high-grade cervical intraepithelial neoplasia in either the colposcopically targeted biopsy specimen or the final excision specimen.