Abnormal cervicovaginal cytology with negative human papillomavirus testing

Human papillomavirus (HPV) testing has become part of cervicovaginal diagnostics in many laboratories. False-negative HPV results, even if rare, are potentially relevant clinically, particularly when testing is used alone. In this study, the authors investigated the occurrence and causes of abnormal cervicovaginal cytologies with negative HPV testing.

The study was performed on 4130 liquid-based cytology (LBC) specimens from 2918 women who had abnormal cervical cytology or colposcopy or a history of abnormal cervical smear. HPV testing with Hybrid Capture II was repeated in LBC specimens with obviously atypical cytology (squamous intraepithelial lesion or abnormal squamous cells, cannot exclude high-grade lesion) and initial negative test results. The results were compared with the follow-up results and with the cytologic features of the specimens.

Of 4130 LBC specimens, 94 (2.28%) showed obviously abnormal cells despite negative HPV results, and 50 of those 94 samples (53.19%) were HPV-positive on a repeated testing of the same specimen. Histologic follow-up showed high-grade intraepithelial lesion or carcinoma in 10 specimens that initially were negative for HPV. Eight of those samples were HPV-positive on testing repetition. Both specimens that had persistently negative results had poor-quality cytologic samples at revision.

High-grade lesions may be identified in the follow-up of HPV-negative specimens with abnormal cytology. Testing repetition in patients with discordant cytology may prevent most potentially clinically relevant false-negative HPV results.