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- Title
HPV infection and 5mC/5hmC epigenetic markers in penile squamous cell carcinoma: new insights into prognostics.
- Authors
Santos, Renan da Silva; Hirth, Carlos Gustavo; Pinheiro, Daniel Pascoalino; Bezerra, Maria Júlia Barbosa; Silva-Fernandes, Isabelle Joyce de Lima; Paula, Dayrine Silveira de; Alves, Ana Paula Negreiros Nunes; Moraes Filho, Manoel Odorico de; Moura, Arlindo de Alencar Araripe; Lima, Marcos Venício Alves; Pessoa, Claudia do Ó; Furtado, Cristiana Libardi Miranda
- Abstract
Background: Penile cancer is one of the most aggressive male tumors. Although it is preventable, the main etiologic causes are lifestyle behaviors and viral infection, such as human papillomavirus (HPV). Long-term epigenetic changes due to environmental factors change cell fate and promote carcinogenesis, being an important marker of prognosis. We evaluated epidemiological aspects of penile squamous cell carcinoma (SCC) and the prevalence of HPV infection using high-risk HPV (hrHPV) and p16INK4A expression of 224 participants. Global DNA methylation was evaluated through 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). Results: The incidence of HPV was 53.2% for hrHPV and 22.32% for p16INK4a. hrHPV was not related to systemic or lymph node metastasis and locoregional recurrence, nor influenced the survival rate. P16INK4a seems to be a protective factor for death, which does not affect metastasis or tumor recurrence. Lymph node and systemic metastases and locoregional recurrence increase the risk of death. An increased 5mC mark was observed in penile SCC regardless of HPV infection. However, there is a reduction of the 5hmC mark for p16INK4a + (P = 0.024). Increased 5mC/5hmC ratio (> 1) was observed in 94.2% of penile SCC, irrespective of HPV infection. Despite the increase in 5mC, it seems not to affect the survival rate (HR = 1.06; 95% CI 0.33–3.38). Conclusions: P16INK4a seems to be a good prognosis marker for penile SCC and the increase in 5mC, an epigenetic mark of genomic stability, may support tumor progression leading to poor prognosis.
- Subjects
SQUAMOUS cell carcinoma; PAPILLOMAVIRUS diseases; HISTONE methylation; PAPILLOMAVIRUSES; PENILE cancer; LYMPHATIC metastasis; VIRUS diseases
- Publication
Clinical Epigenetics, 2022, Vol 14, Issue 1, p1
- ISSN
1868-7075
- Publication type
Article
- DOI
10.1186/s13148-022-01360-1