Human papilloma virus status of penile squamous cell carcinoma is associated with differences in tumour-infiltrating T lymphocytes

Abstract

Meta-analyses show that approximately half of all squamous cell carcinomas (SCCs) of the penis are associated with a human papillomavirus (HPV) infection. As data about the tumour microenvironment of HPV-positive and HPV-negative penile carcinomas is scarce and conflicting, we examined tumour-infiltrating lymphocyte populations in such cases. The HPV status of 28 penile SCCs was determined by polymerase chain reaction, while the number and distribution of different lymphocyte populations were analysed by immunohistochemistry on whole sections of paraffin-embedded tumour specimens. The average number of tumour-infiltrating T cells in HPV-associated SCC was higher than in HPV-negative SCC, and their phenotype showed strong polarization towards a T helper 1 and cytotoxic immune response. In addition, we identified more tumour-infiltrating regulatory T cells in HPV-positive carcinomas, which might represent a mechanism of immune evasion. The present study provides further evidence that the tumour microenvironment of HPV-positive carcinomas differs from that of HPV-negative carcinomas.

The Prognostic Value of Immune Factors in the Tumor Microenvironment of Penile Squamous Cell Carcinoma

“…The difference in patient outcomes between hrHPV + and non-virally induced penile cancer may be partially explained by different immune escape mechanisms ( 8 – 14 ). Surely, immunosuppressive and immunostimulating factors in the tumor microenvironment (TME) co-determine the course of disease in many different cancers, but relatively little is known about penile SCC ( 15 , 16 ).…”

“…In penile cancer, various immune escape mechanisms in the TME have been studied (partly by our group) ( 8 – 14 ). In a multivariable analysis by Vassallo et al, presence of FoxP3-positive lymphocytes (presumably Tregs) was associated with poor disease free survival ( 10 ).…”

Pathophysiological basis of human papillomavirus in penile cancer: Key to prevention and delivery of more effective therapies

“…HPV infection induces an immune reaction in an immunocompetent host, which leads to the generation of HPV‐specific memory T lymphocytes. Lohneis et al have suggested that the tumor microenvironment in HPV‐positive carcinomas is different from that in HPV‐negative carcinomas . Although additional studies are required to confirm this, one can hypothesize that the penile tumors with intense immune cell infiltrate are HPV‐positive and may respond to antiprogrammed cell death protein 1 (PD‐1) drugs.…”

“…Lohneis et al have suggested that the tumor microenvironment in HPV-positive carcinomas is different from that in HPV-negative carcinomas. 51 Although additional studies are required to confirm this, one can hypothesize that the penile tumors with intense immune cell infiltrate are HPV-positive and may respond to antiprogrammed cell death protein 1 (PD-1) drugs. These drugs are currently being researched in other HPV-mediated cancers.…”

The role of human papillomaviruses in cancer progression

“…Penile cancers are rare and they usually occur in uncircumcised men. [176] About half (40-50%) of the penile squamous cell carcinomas are related to the high risk HPV infection [52,[177][178][179][180] and mostly the basaloid and warty types of penile cancers are consistently related to HPV infection, whereas HPV DNA was only detected in some of the keratinizing and verrucous penile carcinomas. [179] Mainly HPV16 (69%) and HPV18 (13%) play a role in the development of penile squamous cell carcinomas.…”