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An Analysis of High-Risk Human Papillomavirus DNA-Negative Cervical Precancers in the ASCUS-LSIL Triage Study (ALTS)

2008; Lippincott Williams & Wilkins; Volume: 111; Issue: 4 Linguagem: Inglês

10.1097/aog.0b013e318168460b

1873-233X

Philip E. Castle, J. Thomas Cox, José Jerónimo, Diane Solomon, Cosette M. Wheeler, Patti E. Gravitt, Mark Schiffman,

Genital Health and Disease

In Brief OBJECTIVE: To describe women diagnosed with cervical intraepithelial neoplasia-grade 3 (CIN-3) diagnosed over the 2-year duration of the atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL) Triage Study (ALTS) that tested negative for high-risk human papillomavirus (HPV) at enrollment. METHODS: Clinical center pathologists and quality control pathology group reviewed all histology; any CIN-3 diagnosis on biopsy or loop electrosurgical excision procedure (n=621) by at least one pathology review over the duration of ALTS led to inclusion in this analysis. Enrollment cervical specimens were tested for high-risk HPV DNA by two HPV assays; results were combined to minimize simple testing errors. We compared the characteristics of baseline high-risk HPV-negative (n=33) to baseline high-risk HPV-positive (n=588) cumulative diagnosed CIN-3. RESULTS: High-risk HPV-negative CIN-3 cases were less likely to have a second, confirming diagnosis of CIN-3 (24% compared with 56%) by the other pathology group, were more likely to be diagnosed later in follow-up, and more likely to be referred into ALTS because of an ASCUS Pap test rather than an LSIL Pap. Upon review of case histories of the 33 baseline high-risk HPV-negative CIN-3 (5.3% of all cases), there was evidence that these cases were due to incident (new) cases (n=12, 1.9%), non–high-risk HPV (n=5, 0.8%), misclassified histology (n=8, 1.3%), and false-negative high-risk HPV (n=8, 1.3%). CONCLUSION: In any sizeable population, even among women with evidence of cytologic abnormalities, there will be a few cases of cervical precancer that will test high-risk HPV negative for one or more reasons. LEVEL OF EVIDENCE: II Finding cervical intraepithelial neoplasia grade 3 within 2 years after a negative human papillomavirus test is uncommon but can result from new disease, false-negative human papillomavirus tests, non–high-risk human papillomavirus genotypes, or misclassified (false-positive) histology.