Impact of HPV in proteomic profile and response to immunotherapy in head and neck cancer

Author(s)

Marisol Miranda Galvis

• Document type: Doctoral Thesis
• Press: Piracicaba, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Odontologia de Piracicaba
• Defense date: 2019-10-18

Examining board members

Luiz Paulo Kowalski; Cristiane Helena Squarize; Claúdia Malheiros Coutinho Camillo; Edgard Graner

• Advisor: Adriana Franco Paes Leme; Luiz Paulo Kowalski

Abstract

Molecular mechanisms of high risk-human papillomavirus (HR-HPV) oncogenesis in oropharyngeal tumors are already established and described in the literature. A recent study proposed to determine the prevalence of 17 subtypes of HR-HPV, revealed a high frequency of HPV DNA 16, in oral squamous cell carcinoma (OSCC) in young patients. The role of the HR-HPV transcriptionally inactive in these tumors is unexplored. In addition, it has been demonstrated that HPV infection influences the response to head and neck cancer treatment, with better survival rates. Therefore, this thesis aimed to evaluate the impact of HPV on the proteomic profile in order to explore the role of HR-HPV in the development and progression of OSCC, as well as, its influence on the response to immunotherapy for head and neck cancer. For this purpose, islands of neoplastic epithelial cells of 20 OSCC affecting patients younger than 40 years old in advanced clinical stage were laser microdissected for mass spectrometric analysis. Subsequently, the results were validated in a tissue microarray, and in vitro assays with OSCC cell lines HPV positive and negative allowed to research the biological function of previously identified proteins. In addition, we conducted a systematic review and meta-analysis of clinical trials evaluating the efficacy and safety of immunotherapy for head and neck cancer, with focus on the response of HPV-associated tumors. The results showed that the proteomic profile of HR-HPV DNA positive OSCC differs from HR-HPV DNA negative. HPV-associated tumors exhibited overexpression of S100A8 protein, and activation of the protein pathway led to a pro-inflammatory response only in HPV-positive tumors, suggesting that the presence of the virus may lead to a modification in the tumor microenvironment with a supposed influence in oral carcinogenesis. On the other hand, the systematic review and meta-analysis demonstrated that immunotherapy improves overall response and survival rates with a reduction in the toxicities in patients treated for head and neck cancer, and a greater benefit was observed in HPV-associated tumors (AU)

• FAPESP's process: 16/03248-1 - Mass spectometry based proteomic in oral squamous cell carcinoma in young patients
• Grantee: Marisol Miranda Galvis
• Support Opportunities: Scholarships in Brazil - Doctorate