Clinicopathologic characteristics of human papillomavirus (HPV) infection and serum anti-HPV 16/18 antibodies in cervical neoplasia

Abstract

Objective: To evaluate the serum anti-HPV 16/18 antibody and cervical HPV DNA status according to the disease severity of cervical neoplasia and also to evaluate the prognostic value of serum anti-HPV16/18 antibody in patients with cervical cancer.Materials and Methods: This study was conducted at the Gangnam Severance Hospital between July 2002 and December 2010. Data were analyzed in patients with a histopathological diagnosis of cervical intraepithelial neoplasia (CIN) 1 (n=64), CIN 2/3 (n=241), cervical cancer (n=170), and in women with no cervical lesion and with normal cytology (n=975). Cervical HPV DNA tests were performed by Hybrid Capture II tests and serum anti-HPV 16/18 antibody was measured by multiplexed competitive Luminex immunoassay. Results were evaluated by epidemiological risk factors and compared according to disease severity. Serum anti-HPV 16/18 antibody was also compared with histopathologic parameters, and clinical follow-up data to assess prognostic value in patients with cervical cancer.Results: Both cervical HPV DNA titer and positivity were significantly increased in patients with cervical neoplasia compared to normal cytology (P <0.001) and although cervical HPV DNA titer was increased in cervical cancer compared to CIN 1 (P = 0.049), overall there was no significant difference in cervical HPV DNA titer and positivity according to the severity of cervical neoplasia. Serum anti-HPV 16 antibody titer was significantly increased in CIN 2/3 and cervical cancer compared to CIN 1 and normal cytology (P <0.001), but there was no significant difference between CIN 1 and normal cytology and between CIN 2/3 and cervical cancer. HPV 16 seropositivity significantly increased according to the disease severity up to CIN 2/3 but there was no significant difference between CIN 2/3 and cervical cancer (P = 0.054). For HPV type 18, there was no significant difference in the antibody titer and seropositivity according to the disease severity. In cervical cancer, HPV 16 seropositivity was significantly associated with longer disease-free survival (P = 0.044) in the univariate analysis but was not proven in the multivariate analysis. Kaplan-Meier survival estimates revealed HPV 16 seropositivity was significantly associated with better disease- free survival (P=0.017).Conclusions: Cervical HPV DNA and serum anti-HPV 16 antibody detection maybe useful in cervical screening as an adjuvant test revealing cervical neoplasia. Serologic detection of anti-HPV 16 antibodies has the advantage of representing a more advanced cervical neoplasia (more than CIN 2) and also may have the possibility for a favorable prognostic value in cervical cancer.