About this Research Topic
Penile cancer is an extremely rare and uncommon malignant tumor which typically accounts for less than 1% of carcinomas found in males in the United States. However, penile cancer has been found to be more prevalent in areas including Africa, Asia and South America. The regional differences play a key factor in the etiology of penile cancer as risk factors include inflammation, smoking, phimosis, poor personal hygiene such as obesity, and particularly human papillomavirus (HPV) infection, which is linked to an average of 40-50% of penile cancer cases. There are multiple HPV subtypes, where HPV-6, 16 and 18 have been found to be associated with the development of penile cancer.
Penile cancer is most commonly treated with surgical resection dependent on the stage of the tumor. The involvement of the lymphatic system has been found to be a prognostic factor for survival outcome of penile cancer patients. Penile cancer with no involvement from the lymph nodes has a 5-year survival of 96% compared to patients with nodal groups such as N1 (80%), N2 (66%) and N3 (37%) have an overall decreasing survival rate. In patients who have locally advanced penile carcinoma which is typically treated by a combination with neoadjuvant chemotherapy and chemotherapy combined with cisplatin, paclitaxel and ifosfamide as well as surgical lymph node dissection, there has been found to be poor prognosis due to 70% of patients experiencing recurring disease. Therefore, it is essential to find other means and therapies towards the treatment of penile cancer.
The field of immunotherapies for cancer has been a breakthrough in the field of emerging therapies. Immune checkpoint inhibitors (ICB) have drastically improved treatment outcomes for cancer patients and have been an alternative approach to treatment due to patients' resistance to conventional chemotherapy. Patients with metastatic penile cancer were shown to express high levels of programmed cell death protein-1 (PD-L1), a monoclonal antibody, found in both primary and metastatic samples. It was further found that 32-62% of squamous cell penile cancers also tested positive for PD-L1 expression and therefore, this may serve as a potential prognostic biomarker as a response to immunotherapy.
Genetic studies have been performed to evaluate copy number alternations (CNAs), somatic changes causing the amplification or deletion of DNA fragments, specifically in genes associated with penile cancer. These have been found to act as a risk factor as CNAs contribute to the progression of cancer via inappropriate activation of proto-oncogenes and the inactivation of tumor suppressor genes. There have been some CNAs in genes including PIK3CA, IL-22 and MYC but further studies are required to help understand the genetic risk factors in penile cancer.
Penile cancer remains a rare malignant tumor which needs to be further studied to understand the influences and impact from a range of risk factors, more prevalent in specific regional areas. Therefore, this Research Topic wishes to discuss the following areas:
-Impact of chemotherapy on metastatic penile squamous cell carcinoma
-Emerging drug therapies targeting penile cancer
-Influence of HPV on penile cancer
-Impact of lymph node count and density from survival of penile cancer
-Immunotherapy in penile cancer
-Genetic risks of penile cancer
Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.
Keywords: penile cancer, genitourinary oncology, chemotherapy, lymph node, metastatic penile squamous cell carcinoma, pembrolizumab, drug therapy
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