Molecular pathways in vulvar squamous cell carcinoma: implications for target therapeutic strategies

• Published in: Journal of cancer research and clinical oncology Vol. 146; no. 7; pp. 1647 - 1658
• Main Authors: Giulia Mantovani, Fragomeni, Simona Maria, Inzani, Frediano, Fagotti, Anna, Della Corte, Luigi, Gentileschi, Stefano, Tagliaferri, Luca, Zannoni, Gian Franco, Scambia, Giovanni, Garganese, Giorgia
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.07.2020; Springer Nature B.V
• Subjects: Angiogenesis; Biomarkers; Cancer Research; Carcinogenesis; Cell cycle; Clinical trials; Epidermal growth factor receptors; Gene amplification; Genital cancers; Hematology; Human papillomavirus; Immunosuppressive agents; Internal Medicine; Literature reviews; Medical prognosis; Medicine; Medicine & Public Health; Molecular modelling; Monoclonal antibodies; Oncology; p53 Protein; PD-1 protein; PD-L1 protein; Pembrolizumab; Prognosis; Review – Cancer Research; Squamous cell carcinoma; Targeted cancer therapy; Vascular endothelial growth factor; Molecular pathways; Vulvar neoplasms; Prognosis; Treatment; Genes; Disease-free survival; Mutation
• ISSN: 0171-5216; 1432-1335
• DOI: 10.1007/s00432-020-03226-6

Background Additional prognostic factors and personalized therapeutic alternatives for vulvar squamous cell carcinoma (VSCC), especially for advanced stages with poor prognosis, are urgently needed. Objectives To review and assess literature regarding underlying molecular mechanisms of VSCC target therapeutic and prognostic approaches. Methods We performed a narrative literature review from the inception of the database up to January 2020 limited to English language, organizing knowledge in five main fields: extracellular and intracellular cell cycle deregulation, tumor immune microenvironment, tumor angiogenesis and hormones. Results EGFR immunohistochemical overexpression/gene amplification, representing early events in VSCC carcinogenesis, have been correlated with a worse prognosis and led to inclusion of erlotinib in cancer guidelines. p16 expression and HPV positivity are linked to a better prognosis, while p53 overexpression is linked to a worse prognosis; thus, biomarkers could help tailoring conventional treatment and follow-up. The implications of PD-L1 positivity in reference to HPV status and prognosis are still not clear, even though pembrolizumab is part of available systemic therapies. The role of tumor angiogenesis emerges through data on microvessel density, immunohistochemical VEGF staining and evaluation of serum VEGF concentrations. Few data exist on hormonal receptor expression, even though hormonal therapy showed great manageability. Conclusions We suggest adding p16, p53 and HPV status to routine hystopathological examination of vulvar biopsies or surgical specimens. Predictive biomarkers for anti-EGFR and anti-PD-1/PD-L1 drugs are needed. Enough preclinical data supporting anti-angiogenic target therapies in clinical trials are existing. Hormonal receptor expression deserves further investigation.