Sabrina Iqbal
Pronouns: She/Her/Hers
UROP Fellowship: Women and Gender Summer Fellowship Program
Research Mentor(s): Guadalupe Lorenzatti Hiles, PhD, MS
Department of Otolaryngology
Presentation Date: Monday, July 27, 2020 | Session 2 | Presenter: 2
Authors: Sabrina Iqbal, Guadalupe Lorenzatti Hiles, Chun-I Wang, Christine M Goudsmit, Lila Peters, Mohammed Charara, Reem A Khatib, Devraj Som, George M Bloom, Hannah L Briggs, Macy A Afsari, Brianna L Moglianesi, Darcy D Huang, Kai-Ping Chang*, Thomas E Carey*, Heather M Walline*
*co-senior authors
Abstract
Background: Oropharyngeal cancer (OPC) is commonly caused by human papillomavirus (HPV), a DNA virus transmitted through sexual contact that infects and transforms the cells of the epithelium. Besides HPV, other causes of OPC are heavy alcohol consumption and other risk behaviors such as smoking and betel quid chewing. To date, few studies have addressed the specific molecular characteristics and potential treatments for HPV-induced OPCs in women, especially in Taiwan, where OPC has been long considered a disease affecting solely men. However, we recently showed that both men and women suffer from OPC in Taiwan, but presumably due to different drivers as women are less likely to be drinkers and smokers and have a higher proportion of HPV-driven tumors. In general, HPV-positive tumors are characterized by the expression of wild-type p53 and respond better to therapy. HPV-negative tumors are frequently driven by mutant p53 and are more prone to fail treatment and must be treated more aggressively. The purpose of this project is to understand how OPC manifests itself differently in Taiwanese women and men at the molecular level by analyzing their driving agents, HPV or mutant p53, and their associations with patient outcome.
Methodology: We obtained 541 oropharyngeal tumors from patients treated in Taiwan between 1998 and 2016 with known clinical data and HPV status. Of these, 34 (6.3%) cases were females. The tumors were stained using standard immunohistochemistry for the OPC biomarkers p16, Rb, cyclin D1, p53, and EGFR. The stained tumors were analyzed using brightfield microscopy to score the biomarkers’ expression according to their intensity and proportion of stained tumor cells. Next, we will use multivariable biostatistical analysis to assess whether there is a correlation between the biomarkers and HPV-status as well as alcohol consumption in the female and male groups. Survival analyses will also be conducted to understand the prognostic effects of biomarkers and alcohol consumption in men and women.
Expected Results and Conclusion: We believe that distinct molecular differences will be present between Taiwanese men and women because women are less likely to have a combination of agents causing OPC such as smoking, betel quid, and alcohol. Taiwanese men, on the other hand, are expected to have a more complex carcinogenesis process of OPC since they are frequently exposed to various risk factors in addition to HPV. Therefore, we expect to find that Taiwanese women will have a higher proportion of HPV-positive oropharyngeal cancer with wild-type p53, implying that HPV is more likely to be the primary cause of OPC in a larger fraction of the female cases. Furthermore, we expect to find that Taiwanese men will have a variability of wild-type and mutant p53.
Expected Learning Outcome: The student will acquire molecular epidemiological experience, understanding of cancer biology, and biomarkers and molecular drivers of disease in women.
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Research Disciplines
Biomedical Sciences, Natural Sciences, Life Sciences
