Prostate disease and HPV
The exact role of HPV in the development of benign and malignant lesions of the prostate is unclear. However, several studies have demonstrated an association between HPV and prostate disease, including prostate cancer. For this reason, treatment of men who are possible carriers of HPV takes on a much greater significance.
J Clin Microbiol 1990 Mar;28(3):409-12:
Detection of human papillomavirus DNA in prostate gland tissue by using the polymerase chain reaction amplification assay.
McNicol PJ, Dodd JG. Cadham Provincial Laboratory, Winnipeg, Manitoba, Canada.
“Human papillomavirus (HPV) is associated with specific benign and malignant lesions of the epithelial and mucosal surfaces. Of the sexually transmitted types, HPV type 16 (HPV 16) and HPV 18 are commonly associated with severe dysplasia and carcinoma of the uterine cervix.
In men, genital HPV infections which have been studied are manifest as external lesions usually involving types other than 16 and 18. The nature of HPV 16 and 18 infections in men has not been explored. Since the most common neoplasias of the male genital tract involve the prostate gland, we assayed benign hyperplastic and cancerous prostate tumors for the presence of HPV DNA, using type-specific primers in polymerase chain reaction amplifications. Normal prostatic tissue obtained at autopsy was included in the survey. Amplified sequences specific for HPV 16 were found in 14 of 15 benign prostatic hyperplasias and in all of four carcinomas tested. In contrast, HPV 18 was identified in only three benign hyperplasias, which also contained HPV 16 DNA. Four of five normal prostates demonstrated no HPV infection; one contained HPV 16 sequences.
The presence of these oncogenic HPV types in prostate tissues suggests a reservoir for sexual transmission; a potential role for the virus in the etiology of prostatic neoplasia remains to be demonstrated.”
Cancer Res 1999 Feb 15;59(4):823-5:
Increased levels of human papillomavirus type 16 DNA in a subset of prostate cancers.
Serth J, Panitz F, Paeslack U, Kuczyk MA, Jonas U. Department of Urology, Hannover Medical School, Germany.
“Whether oncogenic human papilloma viruses (HPVs) are involved in the pathogenesis of prostate cancers has been a subject of great controversy. To clarify the contradictory results of investigations, with the aim of detecting viral nucleic acids in prostate cancers, we have carried out a comparative quantitation of the HPV16-E6 sequence in 84 prostate specimens. Using single-tube quantitative competitive PCR, we characterized 47 prostate cancers and 37 control tissues of benign prostatic hyperplasia. A subgroup of the prostate tumors (10 of 47; 21%) was detected as having significantly higher copy numbers of HPV16-E6 sequences when compared to the control tissue (1 of 37; 3%), using a cutoff value of 300 copies per 12,500 diploid cells (two-sided Fisher's exact test, P = 0.02).
Our results indicate that the oncogenic HPV16 might contribute to the development of a subset of prostate tumors.”
Prostate 1996 May;28(5):318-24:
Detection of human papillomavirus DNA and p53 gene mutations in human prostate cancer.
Suzuki H, Komiya A, Aida S, Ito H, Yatani R, Shimazaki J. Department of Urology, School of Medicine, Chiba University, Japan.
“The relationship between integration with human papillomavirus (HPV) and p53 gene mutations in tissues of prostate cancer were examined. Tissue samples analyzed were obtained by total prostatectomy (29 stage B cancer cases) and from autopsy (22 endocrine therapy-resistant metastatic disease cases). HPV DNA was detected in 8 of 51 (16%, 5 in stage B and 3 in autopsy cases) by polymerase chain reaction (PCR) using consensus primers on L1 region. Genotypes of HPV were entirely type 16. Structural abnormalities of p53 gene were detected in 7 of the 22 autopsy cases (32%) by PCR-single-strand conformation polymorphism analysis and direct sequencing. No p53 gene mutation was found in stage B cancer cases. Analysis of mutation spectra revealed clear differences between Japanese and Westerners. There was a significant difference in the mutation frequency between stage B and autopsy cases (p < 0.01, Fisher's exact test). One case showed both integration of HPV and p53 gene mutation in different cancer foci. However, the other cases revealed an inverse correlation between the presence of HPV DNA and p53 gene mutations. These data show that p53 genetic alteration is correlated with the progression of prostate cancer, in contrast to the integration of HPV that may occur in a relatively early stage.
In conclusion, this study may indicate that either p53 gene mutation or the presence of HPV's oncogenic protein E6 is involved in the development of prostate cancer.”
Int J Cancer 1995 Apr 21;64(2):124-9:
ras, p53 and HPV status in benign and malignant prostate tumors.
Moyret-Lalle C, Marcais C, Jacquemier J, Moles JP, Daver A, Soret JY, Jeanteur P, Ozturk M, Theillet C. Institut de Genetique Moleculaire de Montpellier, France.
“To study the role of ras, p53 genes and HPV virus (16 and 18) in the development of prostate cancer, we analyzed tissue sections from 27 patients affected with carcinomas (stages A to D) and from 24 patients with adenomas. Mutations of H, K and N-ras and p53 (exons 2-9) were studied by SSCP and DNA sequencing. Accumulation of p53 protein was studied by immunohistochemistry on tissue sections. Tumors were also analyzed for the presence of HPV16 and -18 sequences by PCR and DNA hybridization with sequence-specific oligonucleotides. No mutation was found in the three ras genes studied, either in carcinomas or adenomas. By SSCP analysis we identified p53 mutations in only 2 of 19 carcinomas studied, both in exon 7. Immunohistochemical results strongly correlate with the SSCP results: p53 protein was positive in tumors with p53 mutation but not in others; 32% of studied adenomas had detectable HPV16 DNA, while 53% of carcinomas were HPV16+. No HPV18 E6 sequence could be detected. Our data show that in prostate tumors from France, mutations of p53 and ras are rare events but that these tumors display detectable HPV16 DNA at a high frequency.
The low incidence of p53 mutation, associated to a significant proportion of tumors showing HPV16 DNA, could suggest that in prostate cancer HPV16 infection could participate in p53 inactivation by E6.”