Is human papillomavirus associated with prostate cancer survival?

Abstract

The role of human papillomavirus (HPV) in prostate carcinogenesis is highly controversial: some studies suggest a positive association between HPV infection and an increased risk of prostate cancer (PCa), whereas others do not reveal any correlation. In this study, we investigated the prognostic impact of HPV infection on survival in 150 primary PCa patients. One hundred twelve (74.67%) patients had positive expression of HPV E7 protein, which was evaluated in tumour tissue by immunohistochemistry. DNA analysis on a subset of cases confirmed HPV infection and revealed the presence of genotype 16. In Kaplan-Meier analysis, HPV-positive cancer patients showed worse overall survival (OS) (median 4.59 years) compared to HPV-negative (median 8.24 years, P = 0.0381). In multivariate analysis age (P < 0.001), Gleason score (P < 0.001), nuclear grading (P = 0.002), and HPV status (P = 0.034) were independent prognostic factors for OS. In our cohort, we observed high prevalence of HPV nuclear E7 oncoprotein and an association between HPV infection and PCa survival. In the debate about the oncogenic activity of HPV in PCa, our results further confirm the need for additional studies to clarify the possible role of HPV in prostate carcinogenesis.

Figure 1

Tests for specificity of the analysis. Preabsorption test to verify the specificity of the E7 signal on prostate cancer samples. Immunostaining with the Cervimax IHC kit in prostate cancer tissue (a) and after preabsorption with the specific oncoviral peptide (b). Original magnification: 20x; conventional immunohistochemistry performed with diaminobenzidine as a chromogen and hematoxylin for counterstaining. PCR amplification of HPV DNA is reported in (c): MW molecular weight marker, 1–22 amplification carried out in prostate cancer specimens. In 19 cases positive for HPV E7 IHC, 18 were PCR positive and 1 was PCR negative (sample 10). Of those successfully sequenced samples were 4, 7, 8, 9, 13, 14, 15, 17, and 21. Sequencing failed in samples 1, 2, 3, 5, and 6. Samples 12, 16, and 20 refer to amplification carried out in prostate cancer cases negative for HPV E7 immunodetection.

Figure 2

Representative immunohistochemistry staining of E7 for prostate intraepithelial neoplasia (PIN2) (a); prostate adenocarcinomas (b), (c), and (d); original magnification: 20x; conventional immunohistochemistry performed with diaminobenzidine as a chromogen and hematoxylin for counterstaining.

Figure 3

Survival curves by HPV E7 nuclear expression in 150 patients with primary prostate cancer. P value from log-rank test is reported. Numbers of at risk (still alive) patients are indicated below the x-axis.