Identification and genotyping of human papillomavirus in a Spanish cohort of penile squamous cell carcinomas: Correlation with pathologic subtypes, p16INK4a expression, and prognosis

Ferrándiz-Pulido, Carla; Masferrer, Emili; Torres, Inés de; Lloveras, Belén; Hernández-Losa, Javier; Mojal, Sergi; Salvador, Carlos; Moróte, Juan; Cajal, Santiago Ramón y; Pujol, Ramón M.; García‐Patos, Vicente; Toll, Agustí

doi:10.1016/j.jaad.2012.05.029

Cited by 65 publications

(37 citation statements)

References 46 publications

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“…We found that the majority of HPVpositive but only one HPV-negative carcinoma showed strong and consistent nuclear and cytoplasmic expression of the p16 protein, indicating a transcriptionally active HPV infection in most HPV-positive carcinomas. Other studies reported similar results and established p16 as a reliable marker for HPV infection [9,28,29]. In our study, most keratinizing moderately and all well-differentiated SCCs were HPV DNA negative, while all basaloid and the warty-type SCCs were HPV DNA positive.…”

Section: Discussionsupporting

confidence: 86%

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

et al. 2014

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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.

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Section: Discussionsupporting

confidence: 86%

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

et al. 2014

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“…Previous studies have generally shown HPV and p16 positivity to associate with favorable prognosis (17,(21)(22)(23). Likewise, although exploratory due to the limited number of samples with alterations and events, MYC and CCND1 amplifications were both significantly associated with decreased event-free survival.…”

Section: Discussionmentioning

confidence: 94%

Genomic Profiling of Penile Squamous Cell Carcinoma Reveals New Opportunities for Targeted Therapy

et al. 2015

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Penile squamous cell carcinoma (PeSCCA) is a rare malignancy for which there are limited treatment options due to a poor understanding of the molecular alterations underlying disease development and progression. Therefore, we performed comprehensive, targeted next-generation sequencing to identify relevant somatic genomic alterations in a retrospective cohort of 60 fixed tumor samples from 43 PeSCCA cases (including 14 matched primary/metastasis pairs). We identified a median of two relevant somatic mutations and one highlevel copy-number alteration per sample (range, 0-5 and 0-6, respectively). Expression of HPV and p16 was detectable in 12% and 28% of patients, respectively. Furthermore, advanced clinical stage, lack of p16 expression, and MYC and CCND1 amplifications were significantly associated with shorter time to progression or PeSCCA-specific survival. Notably, four cases harbored EGFR amplifications and one demonstrated CDK4 amplification, genes for which approved and investigational targeted therapies are available. Importantly, although paired primary tumors and lymph node metastases were largely homogeneous for relevant somatic mutations, we identified heterogeneous EGFR amplification in primary tumor/lymph node metastases in 4 of 14 cases, despite uniform EGFR protein overexpression. Likewise, activating HRAS mutations occurred in 8 of 43 cases. Taken together, we provide the first comprehensive molecular PeSCCA analysis, which offers new insight into potential precision medicine approaches for this disease, including strategies targeting EGFR.

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“…5 Of the cases 35.9% harbored HPV infection, which corresponded to high risk HPV (mainly HPV16) in 95.7%.…”

Section: Clinical and Clinicopathological Featuresmentioning

confidence: 95%

“…5 Briefly, we detected HPV DNA by polymerase chain reaction. The polymerase chain reaction products were analyzed to detect at least 54 mucosal HPV types by DNA enzyme immunoassay.…”

Section: Human Papillomavirusmentioning

confidence: 99%

“…In contrast to cervical cancer, in which HPV is found in 100% of cases, HPV related lesions are more common in some PSCC subsets, such as the basaloid and warty subtypes. 5 HPV products E6 and E7 have crucial roles in carcinogenesis by targeting tumor suppressor p53 and retinoblastoma proteins, respectively. In addition, HPV is also associated with surface E-cadherin deregulation in benign epithelial lesions, tonsillar carcinoma and cervical intraepithelial neoplasia.…”

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confidence: 99%

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Epithelial-to-Mesenchymal Transition in Penile Squamous Cell Carcinoma

et al. 2015

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Identification and genotyping of human papillomavirus in a Spanish cohort of penile squamous cell carcinomas: Correlation with pathologic subtypes, p16INK4a expression, and prognosis

Cited by 65 publications

References 46 publications

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

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

Genomic Profiling of Penile Squamous Cell Carcinoma Reveals New Opportunities for Targeted Therapy

Epithelial-to-Mesenchymal Transition in Penile Squamous Cell Carcinoma

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