Is human papillomavirus genotype an influencing factor on radiotherapy outcome? Ambiguity caused by an association of HPV 18 genotype and adenocarcinoma histology

OBJECTIVE: To evaluate whether human papillomavirus (HPV) genotype is associated with poor prognosis of uterine cervical cancer treated primarily with radiotherapy. METHODS: HPV genotyping was performed in 181 radiotherapy patients using SPF10 polymerase chain reaction and HPV reverse hybridization line probe assay. Univariate and multivariate Cox regression analysis was performed to explore the prognostic factors. Bivariate analysis was performed to investigate any association between HPV genotype and the rest of the prognostic factors. RESULTS: HPV type 18 was associated with poor disease-free survival on univariate analysis but the statistical significance was abolished when multivariate analysis was applied. Bivariate analysis was performed to examine the possible confounding factors influencing the effect of HPV 18 on prognosis. As a result, adeno/adenosquamous carcinoma histology reduced the prognostic importance of HPV 18 by 66% (2.4 to 1.6), and was the only factor which reduced the hazard ratio of HPV 18. When compared to non-18 squamous cell carcinoma, type 18 increased the risk of recurrence up to 4-fold in adeno/adenosquamous/HPV 18 and 3.7 in adeno/adenosquamous/non-18, and to 2-fold in squamous carcinoma/HPV 18, respectively. CONCLUSION: Our data suggest that the prognostic significance of HPV 18 genotype is substantial on radiotherapy outcome, but can be underestimated because of the close association of the HPV 18 and adenocarcinoma/adenosquamous carcinoma histology. Both HPV 18 and histologic type should be regarded as strong prognostic factors in considering the treatment outcome of the uterine cervical cancer.