Prognostic significance of human papillomavirus (HPV) type and nuclear DNA content in invasive cervical cancer

Abstract

Eighty-one women treated for an invasive squamous cell carcinoma of the uterine cervix during the period from 1964 to 1987 were studied to assess the prognostic value of human papillomavirus (HPV) types 6,11, 16 and 18, as well as the nuclear DNA ploidy pattern, analyzed using HPV amplification by polymerase chain reaction (PCR) and flow cytometry, respectively. The mean age of the women was 57.7 ± 13.4 years, and the mean follow-up until the patients death or January 1990 was 99 ± 87 months. Altogether, 46 women died; 38 (82.6%) of these deaths were due to cervical cancer. The 5-year survival was significantly correlated with age (P= 0.01), and the FIGO stage of the tumors (P= 0.015), but not with tumor differentiation. Diploid tumor was found in 40 (63.5%) cases, and aneuploid in 23 (36.5%) cases. A DNA index 3= 1.5 was found in 47.8% (11/23) of the cases of aneuploid tumors. The 5-year survival rate in diploid tumors was 60.0% (21/35), as compared to 54.5% (12/22) in aneuploid ones, and in patients with a DNA index of < 1.5, the 5-year survival rate was 58.7% (27/46), as compared to 54.5% (6/11) in those with a DNA index ≥ 1.5. Amplified HPV DNA was found in 30 cases (37.0%) with the pairs of HPV DNA primers for HPV types of 6, 11, 16 and 18. When repeated with the anticontamination primers, only 19 (23.5%) cases remained HPV DNA positive. HPV 16 was the most frequent type present in 57.9% (11/19) of the cases, followed by HPV 18 in 36.8% (7/19). Neither the HPV DNA-positivity nor HPV type proved to be of prognostic significance. The results suggest that despite an intimate association of HPV 16 and 18 in cervical carcinogenesis, the presence of their DNA in cancer biopsies does not seem to have any prognostic value. The most significant prognostic factors are still the age and the FIGO stage at diagnosis. Aneuploid tumors or those with DNA index ≥ 1.5 seem to have a slightly (not statistically significantly) impaired prognosis as compared with the diploid tumors and those with DNA index < 1.5.