Original contributionHuman papillomavirus infection and immunohistochemical p16INK4a expression as predictors of outcome in penile squamous cell carcinomas☆,☆☆
Introduction
Penile cancer is a malignancy with variable geographic prevalence. Although, in the South American, African, and Asian countries, this neoplasm may be responsible for up to 10% of all cancers in men, in other countries in Europe and North America, the incidence is much lower, not exceeding 1% of male malignancies [1]. The reasons why there are such differences in prevalence seems to be because of epidemiological factors and conditions [2], such as low levels of education, low income, living in rural regions, and poor genital hygiene habits [3]. In addition, heterogeneous distribution of human papillomavirus (HPV) may, in part, explain the geographic variation of penile cancer [4].
The most common histologic subtype of penile cancer is squamous cell carcinoma (SCC) [5]. Infection by HPV plays an important role in the pathogenesis of penile cancer [6], [7] and is associated with certain histologic subtypes [8], [9], [10]. In contrast to uterine cervical cancers, in which most tumors are HPV-related [11], only 30% to 50% of penile cancers show evidence of HPV infection [12], [13], [14].
p16 overexpression has been widely used as a surrogate marker for HPV infection in head and neck SCC and uterine cervical cancers. Notably, it has been shown that p16 expression is not associated with HPV in urothelial neoplasms or SCC of the urinary bladder [15], [16].
Although, in head and neck SCC, the subset of HPV-associated tumors has a better outcome [17], the role of HPV as a prognostic factor in penile cancer remains unclear [18]. The data on the association between HPV status and survival in penile tumors have, so far, been inconsistent [7].
The main objective of this study was to evaluate the correlation of immunohistochemistry for p16INK4a expression and in situ hybridization (ISH) for high-risk HPV (HR-HPV) detection with clinicopathological features of penile carcinoma as well as correlate the findings with outcome in a cohort of patients with long-term follow-up.
Section snippets
Materials and methods
This study was approved by the institutional review board of The Johns Hopkins Hospital.
Results
Clinicopathological features of our penile SCC cases are summarized in Table 1. The median age at surgery was 65 years (range, 38-93 years). More than one third of patients were white and the most common histologic subtype was usual SCC. The glans was the most frequent anatomical site of origin. Ninety percent of the patients had partial penectomy as their primary treatment. Regarding outcome, 34% of our patients experienced progression of disease.
Table 2 shows the association of HR-HPV ISH
Discussion
In 1993, Kurman et al [22] were the first to establish an association of HPV with particular types of vulvar cancers, in a pathologic and virological study. Two years later, Gregoire et al [13] found a correlation between subtypes of penile SCCs and HPV. In these studies, a preferential association of HPV with the basaloid and mixed warty and basaloid types of SCC was demonstrated, whereas HPV was consistently negative in verrucous and papillary types of SCC.
Given that the incidence of penile
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Competing interests: The authors have disclosed that they have no significant relationships with or financial interest in any commercial companies pertaining to this article.
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Funding/Support: This work is partially supported by The Brady Urological Institute – Johns Hopkins Medicine Patana Fund.