Comparative evaluation of nm23 and p16 expression as biomarkers of high-risk human papillomavirus infection and cervical intraepithelial neoplasia 2(+) lesions of the uterine cervix.

AIMS: To investigate the clinical role of nm23 expression in identifying both high-risk human papillomavirus (HR-HPV) and high-grade cervical lesions or carcinomas [cervical intraepithelial neoplasia 2(+) (CIN2(+) )], and to compare it with p16 overexpression, as this latter biomarker has already been reported widely in HR-HPV infected cervical lesions.

METHODS AND RESULTS: Immunohistochemical evaluation of nm23 and p16 in 143 cervical biopsy specimens including negative, low- and high-grade lesions and squamous carcinomas (SC). HR-HPV testing by Digene hybrid capture 2 (HC2) and polymerase chain reaction (PCR) on the cervico-vaginal samples of the same patients. In detecting CIN2(+) , p16 was significantly more sensitive and specific than nm23 (96.3% versus 81.8% and 66% versus 36.4%, respectively, both P < 0.0001). Concerning HR-HPV detection by HC2, p16 showed a significantly higher specificity than nm23 (82% versus 47%, P <0.0001), although the sensitivities were comparable (71% versus 76%). We found a significantly direct correlation between nm23 and HC2 findings. However, nm23 expression did not correlate with HPV16/18 infection. In contrast, we observed a significant association between p16 overexpression and HPV16/18 genotypes.

CONCLUSIONS: We confirm the diagnostic value of p16 overexpression. Moreover, despite in vitro data regarding the interaction with the HPV-E7 protein, nm23 does not appear to be a more useful biomarker than p16 in identifying CIN2(+) or HR-HPV infection.