Assessment of reflex human papillomavirus DNA testing in patients with atypical endocervical cells on cervical cytology




Reflex human papillomavirus (HPV) testing for atypical squamous cells of undetermined significance (ASC-US) has improved the sensitivity and specificity in detecting high-grade squamous dysplasia (cervical intraepithelial neoplasia [CIN]2+). However, to the authors' knowledge there are no guidelines for performing reflex HPV testing in women with atypical endocervical cells (AEC) before colposcopy. This report is of a 5-year experience with reflex HPV testing in women with AEC and assessment of the potential role of reflex HPV testing in guiding subsequent colposcopy-directed cervical biopsy/curettage in a large tertiary care hospital setting.


All AEC cases cytologically diagnosed from July 2001 to June 2006 were retrieved from the Cleveland Clinic database. The histopathologic diagnoses and the results of HPV testing using the Hybrid Capture 2 (HC-II) method were reviewed. The most severe histopathologic diagnosis was recorded.


Of a total 332,470 Papanicolaou (Pap) tests performed, 317 cases of AEC had histopathologic follow-up and reflex testing for high-risk HPV. Histopathologic examination of the 64 HPV-positive AEC cases revealed 18 cases of endocervical adenocarcinoma in situ/adenocarcinoma (AIS+) and 22 cases of CIN2+. Among 253 of the HPV-negative AEC women, AIS+ was found in only 3 cases and CIN2+ in 1 case. Cervical AIS+ was found in 28% of the HPV-positive AEC patients and in only 0.9% of the HPV-negative patients (P<.0001). When the significant glandular (AIS+) and squamous (CIN2+) lesions were combined, 62.5% of the lesions were detected in HPV-positive AEC cases compared with 1.6% in the HPV-negative AEC cases (P<.0001).


Because of a high sensitivity (91.0%) and high specificity (91.2%) in detecting significant cervical lesions, reflex HPV testing for cytologic diagnosis of AEC appears to be a useful ancillary tool in the selection of high-risk patients for colposcopy. Cancer (Cancer Cytopathol) 2008. © 2008 American Cancer Society.