Correlation between human papillomavirus positivity and p53 gene overexpression in adenocarcinoma of the uterine cervix.

In the pathogenesis of cervical squamous cell carcinoma, an inverse correlation between human papillomavirus (HPV) infection and mutation of the p53 anti-oncogene has been suggested. Much less is known of a possible correlation in the case of adenocarcinoma of cervix. Twenty-five cervical adenocarcinomas and 7 adenosquamous carcinomas were analyzed for presence of HPV DNA sequences and overexpression of the p53 gene. Polymerase chain reaction revealed that 11 were positive for HPV DNA (34%). Seven were positive for HPV 16 and 5 for HPV 18. A mixed infection with HPV 16 and 18 was observed in 1 case. Patients with HPV-positive carcinoma were significantly younger than those with HPV-negative carcinoma (43 +/- 13.3 years versus 57 +/- 17.4 years, P = 0.01). Immunohistochemical staining showed that p53 was overexpressed in 11 of 32 cases (34%). Overexpression of the p53 gene was found in only 1 of 11 HPV-positive cases (9%) yet was evident in 10 of 21 HPV-negative cases (48%). This inverse association was statistically significant (P < 0.05). Prognostic analysis revealed that HPV-negative adenocarcinomas had a poorer prognosis than HPV-positive cases (P < 0.01) and that tumors with p53 overexpression also had a poorer prognosis than those without such overexpression (P < 0.01). Our observations suggest that HPV-negative or p53-positive adenocarcinomas may be a biologically distinct subset with a poorer prognosis.