The analysis of human papillomavirus DNA in penile cancer tissue by in situ hybridization

Abstract

Primary penile cancer is a rare disease. Higher incidence rates occur in underdeveloped countries. Many studies have suggested an association between human papillomavirus (HPV) infection and penile cancer. Although HPV can affect the squamous epithelium of the male genitalia similarly to the female genital tract, the association between penile cancer and HPV remains unclear. In the present study, the HPV gene expression was examined in penile cancer tissue using in situ hybridization (ISH). The present study included 41 cases in which penectomy was performed and 3 cases in which tumor resection was performed to treat pathologically-diagnosed penile cancer at Yokohama City University Medical Center, and its 7 affiliated hospitals between April 1990 and March 2010. The penile cancer tissue was subjected to an ISH analysis, and the clinicopathological features and prognosis were investigated. A total of 5/44 cases (11.4%) showed the expression of high-risk HPV. None of the patients showed the expression of low-risk HPV. The associations between the expression of high-risk HPV, and age, tumor location, tumor size, T stage, pathological differentiation, nuclear grade, Broder's classification, pattern of invasion, Y-K grade, vascular invasion, lymphoid invasion, koilocytosis and lymph-node metastasis were then examined. Patients with a well-differentiated status (P=0.044) and Broder's Grade 1 (P=0.019) showed a significantly lower rate of HPV positivity. The HPV expression was not significantly associated with cancer specific survival (P=0.932). ISH using INFORM HPV III does not detect the HPV genotype, this method is easy to employ and may be useful for the diagnosis of penile cancer tissue, similarly to cervical cancer.

Keywords: human papillomavirus; in situ hybridization; penile cancer.

Figure 1.

Hematoxylin and eosin staining (magnification, ×12.5).

Figure 2.

HPV HR ISH (magnification, ×40). HPV infected cells are shown in blue (black arrows). HPV, human papillomavirus; HR, high-risk; ISH, in situ hybridization.

Figure 3.

HPV HR ISH (magnification, ×400). HPV, human papillomavirus; HR, high-risk; ISH, in situ hybridization.

Figure 4.

Kaplan-Meier curve between the HPV-positive and HPV-negative groups. There were no significant differences in cancer specific survival in terms of HPV positive or not. HPV, human papillomavirus; HR, high-risk.