Abstract
The objective of our study was to assess the performance of different triage strategies for high‐risk human papillomavirus (hrHPV)‐positive results utilizing either extended genotyping or a p16/Ki‐67 dual‐stained cytology (DS) approach, with or without partial genotyping. A subset of women with hrHPV infections participating in the Addressing the Need for Advanced HPV Diagnostics (ATHENA) study were analyzed to determine the number of cervical intraepithelial neoplasia grade 3 or worse (≥CIN3) cases detected, and the absolute risk for ≥CIN3 of each genotype. A clinical utility table was constructed to compare the impact of different triage strategies. In all, 2,339 women with single‐genotype hrHPV infections were identified. Among these were 171 ≥CIN3 cases. The U.S. Food and Drug Administration (FDA)‐approved algorithm (HPV16/18 positive, or 12‐other hrHPV positive and Pap positive, i.e., ≥ atypical squamous cells of undetermined significance) for primary HPV screening detected 132/171 (77.2%) ≥CIN3 cases and required 964 colposcopies (colposcopies per ≥CIN3 ratio: 7.3). An approach that uses DS instead of cytology in the FDA‐approved algorithm detected 147/171 (86.0%) ≥CIN3 cases, requiring 1,012 colposcopies (ratio: 6.9). Utilizing DS for triage of all hrHPV‐positive women identified 126/171 (73.7%) ≥CIN3 cases, requiring 640 colposcopies (ratio: 5.1). A strategy that detected HPV16/18/31/33/35+ captured 130/171 (76.0%) ≥CIN3 cases, requiring 1,025 colposcopies (ratio: 7.9). Inclusion of additional genotypes resulted in greater disease detection at the expense of higher colposcopy ratios. Substituting cytology with a DS triage approach improved disease detection and the colposcopy detection rate. Further reduction of colposcopy rates can be achieved by using DS without partial genotyping. Extended genotyping strategies can identify a comparable number of cases but requires an increased number of colposcopies.
Highlights
There is an evolving worldwide consensus that the best way to screen for cervical cancer is to include high-risk human papillomavirus testing in the initial screening process
The Hybrid Capture 2 human papillomavirus (HPV) test (Qiagen, Hilden, Germany) does not offer partial or extended genotyping, whereas the Aptima® HPV test (Hologic, Marlborough, MA) requires an additional reflex test from the original specimen to perform partial genotyping for HPV16 and 18/45, and the cobas® HPV Test (Roche Molecular Systems Inc, Pleasanton, CA) and the OnclarityTM HPV test (BD Diagnostics, Franklin Lakes, NJ) both offer some degree of integrated genotyping. This leads to the question that we aim to address here: how does extended genotyping compare with dual-stained cytology (DS) testing, with or without partial genotyping, when incorporated into a screening strategy as a triage test for high-risk human papillomavirus (hrHPV)-positive screening results? In this analysis, we utilized data from the Addressing the Need for Advanced HPV Diagnostics (ATHENA) study, with which ≥cervical intraepithelial neoplasia grade 3 (CIN3) outcomes can be evaluated in the context of extended genotyping and DS test results
In the United States, the first Food and Drug Administration (FDA)-approved HPV primary screening algorithm was based on the cobas HPV Test that provides integrated HPV16/18 genotyping, and this algorithm has been incorporated into guideline discussions
Summary
There is an evolving worldwide consensus that the best way to screen for cervical cancer is to include high-risk human papillomavirus (hrHPV) testing in the initial screening process. Multiple studies have documented the superior sensitivity of clinically validated hrHPV testing over Pap cytology for detecting cervical precancer and cancer.[1–3]. This high level of sensitivity leads to maximal reassurance for the great majority of women with screen test negative results. In the United States, cotesting, that is, performing a human papillomavirus (HPV) test and Pap cytology on all screened women in parallel, has been dominant. HPV primary screening has been approved for 5 years, and the most recent United States Preventive Services Task Force screening guidelines prefer primary hrHPV testing every 5 years to cytology every 3 years for screening.[5–7]
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