Human papillomavirus genotypes and P16INK4A expression in squamous penile carcinoma in Mexican patients

Abstract

Background: Approximately 50% of cases of penile carcinoma (PeCa), a rare neoplasm worldwide, are associated with human papillomavirus (HPV). However, the detection of HPV-DNA is not sufficient to consider it the etiological factor in the development of this type of cancer. Currently, the overexpression of P16INK4A is used as a surrogate biomarker of HPV carcinogenesis. Information on PeCa in Mexico is scarce, particularly regarding cases related to HPV and genotype frequency. Objective: To evaluate the presence of HPV, its genotypes, and the presence of multiple genotypes, and the expression of P16INK4A, as well as its clinical and histopathological parameters. Methods: For HPV-DNA detection and P16INK4A expression, we used the INNO-LiPA® test and immunohistochemistry, respectively. Results: Sixty cases of PeCa were evaluated, of which 75% were HPV-non-related histological variants. We found that 58.9% (33/56) of PeCa cases were HPV-DNA positive, while 30.9% of the cases evaluated (17/55) were positive for P16INK4A. HPV16 was the main genotype in 42.9% of the cases, followed by HPV52 in 7.1% and HPV18 in 5.4%. Within the HPV-positive cases, 27.3% had multiple genotypes. All HPV-positive patients under the age of 45 years were positive only for HPV16. Conclusions: HPV16 was the most commonly detected genotype in PeCa. HPV 31, 35 and 39 were infrequent; however, they were related to a single infection and P16INK4A overexpression; thus, they seem to be relevant in PeCa carcinogenesis. Our results suggest that P16INK4A overexpression could be useful for the classification of HPV-related PeCa. The role of multiple HPV genotypes in the development and prognosis of PeCa is still not completely understood. Thus, it is necessary to define criteria to establish reliable ways to classify HPV-related PeCa that could lead to optimal therapeutic approaches.

Presence of HPV with overexpression of p16INK4a protein and EBV infection in penile cancer—A series of cases from Brazil Amazon

“…Degree of poorly differentiated cell could indicate a worse prognosis of lesions. Our findings reinforced other studies observations [43,44].…”

The Impact of Human Papillomavirus Infection on Skin Cancer: A Population-Based Cohort Study

“…In a previous skin biopsy investigation of different oncogenic epitheliotropic viruses, HPV detection was more frequent in NMSC compared to noncancerous biopsies, supporting the role of HPV infection in NMSC development [21]. Alphapapillomaviruses were generally recognized as high‐risk HPV types, especially HPV 16, provoking anogenital, head, and neck cancers [22, 23]. A case report of pigmented Bowen's disease also confirmed the presence of high‐risk HPV types [24].…”

Proteases and HPV-Induced Carcinogenesis

“…In a normal physiological condition, p53 would counteract the effects of exacerbated cell proliferation while activating the cellular DNA damage response (DDR) during viral DNA integra-tion into the host genome, leading to the inhibition of cell growth and apoptosis [48,49]. However, HPV E6 inactivates p53 by targeting its proteasomal degradation and forming a complex with the E3 ubiquitin-protein ligase E6-associated protein, E6AP [50,51]. Moreover, it is also important to highlight the fact that high-risk E6 has been reported to bind the hTERT protein as well as the repeating DNA sequence of telomeric DNA, in addition to controlling telomerase activity [52].…”

“…The HPV alpha and gamma groups infect skin and mucosal tissue, whereas the beta-, nu-and mu-subtypes infect cutaneous sites, even without clinical manifestations [27,28]. All of the 12 HPV genotypes that are classified as group 1 carcinogens belong to the alpha genus: HPV16, 18,31,33,35,39,45,51,52,56,58, and 59 [29]. Indeed, alpha-HPVs are transmitted through sexual contact, and can be considered the leading group of causative agents of sexually transmitted infections globally [28].…”