The status of human papillomavirus and tumor suppressor genes p53 and p16 in carcinomas of uterine cervix from India

Abstract

Objectives: Infection with the high-risk strain of human papillomaviruses (HPVs) and the inactivation of the tumor suppressor genep53through mutation are important factors in cervical carcinogenesis. To know whether such events would occur in cervical carcinomas of Indians, 43 tumors (consisting of 36 of stage III B and 6 of stage II B) were screened for p53 and p16gene mutations. Methods: PCR followed by single-strand conformation polymorphism (SSCP) analysis were used to detect mutations in p53andp16genes and PCR for the presence of human papillomavirus genome. HPV status was ascertained by PCR amplification of parts of E6 and E7 genes using primers pU-1M and pU-2R and typing was carried out by restriction analysis. Results: Of the 43 samples analyzed, 4 samples (9%) showed mobility shifts for p53 mutations; PCR products of thep16gene did not show band shifts in SSCP analysis. HPV DNA was detected in 70% of the 43 samples analyzed: HPV 16 in 23 cases (53%), HPV 18 in 4 cases (13.3%), and HPV 33 in 1 case (3.3%). Two amplified HPV DNAs that were difficult to type with various restriction enzymes were cloned and the amplified regions were sequenced. One of these was 93% close to HPV 35 and the other was 80% close to HPV 58. Three samples had both p53 mutations and HPV genome. Conclusions: Our results indicate that HPV 16 infection was more common than HPV 18, the p53 mutations and HPV infection were not mutually exclusive events in the genesis of carcinoma of uterine cervix among Indian women, andp16gene may not play a role in Indian cervical carcinomas.