Non-16/18 HR-HPV Genotypes Are Superior to HPV 16/18 for Predicting High-Grade Intraepithelial Lesions in LEEP Resections
Haijun (Steve) Zhou, Dina Mody, Mary Schwartz, Yimin Ge. Methodist Hospital, Houston, TX
Background: HPV 16 and 18 are responsible for the majority of cases of high-grade squamous intraepithelial lesions (HSIL) and cervical cancer. While HPV 16/18 have been extensively studied, more than a dozen non-16/18 high risk HPV (HR-HPV) genotypes have been overshadowed by the two leading HPV types and have received much less attention. With the current vaccines directed against HPV 16/18, non-16/18 HR-HPV genotypes are expected to play an increasing role in cervical cancer screening and prevention. Therefore, evaluating the predictive value of non-16/18 type HR-HPV is pertinent for early detection and cancer prevention, as well as for future vaccine development.
Design: A cohort of 808 SurePath specimens were collected from women who were referred to our institution from 12/2009-4/2011 for abnormal Pap tests. HPV genotypes were determined by DNA microarray against 40 HPV subtypes followed by a confirmatory sequencing assay. Forty-three patients from the cohort had a concurrent or subsequent LEEP procedure. Correlations among HPV genotype, cytologic findings and LEEP findings were analyzed.
Results: The HR-HPV infection rate was 81.4% in the 43 patients who underwent a LEEP and 94.4% in patients with HSIL on Pap tests. Cytologic interpretation of HSIL had 88.9% positive predictive value (PPV) for any grade of dysplasia and 83.3% for CIN 2 and above lesions in LEEPs. The PPV of non-16/18 HR-HPV for any grade of dysplasia in LEEPs was 93.3%, which was significantly better than that of HPV 16/18 (65%, p=0.049). For patients with CIN 2 and above lesions in LEEPs, the PPV of non-16/18 HR-HPV (73.3%) was also better than that of HPV 16/18 alone (58.3%). HPV 31/52/58/39/45 genotypes were commonly detected in women with HSIL in LEEP specimens. Furthermore, all patients with HPV31/52/58 infection documented on Pap test had HSIL in LEEP (100% positive predictive value).
Conclusions: The predictive value of non-16/18 HR-HPV genotypes for HSIL in LEEPs was superior to that of the HPV 16/18 test. The HPV16/18-only test may be not having as a high value as perceived, and a negative result may give a false assurance, especially in high risk populations. In addition to HPV 16/18, an expanded test panel of HR-HPV genotypes to include some of the non-16/18 genotypes with high PPV (such as HPV 31/52/58) may be warranted. At the present time, testing with a cocktail of HR-HPV types appears to offer a better predictive value for HSIL than using an HPV 16/18 test.
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 62, Monday Morning