A Comparative Study on HPV-negative Vs. HPV-positive OPSCC

Abstract

This project explores the differences between HPV-positive and HPV-negative oropharyngeal squamous cell carcinoma (OPSCC), focusing on causes, pathology, prognosis, and treatment outcomes. HPV-positive OPSCC is primarily caused by persistent infection with HPV16, leading to oncogenesis via viral oncoproteins E6 and E7, which disrupt tumor suppressor proteins p53 and Rb1. In contrast, HPV-negative OPSCC is associated with lifestyle factors such as tobacco use, alcohol consumption, and betel quid chewing, leading to mutations in tumor suppressor genes like TP53, Rb1, and oncogenes like KRAS and PIK3R1. Epidemiological data indicates that HPV-positive OPSCC has a better prognosis, with a 5-year survival rate of 75% compared to 50% for HPV-negative OPSCC. HPV-negative cases tend to have a higher mutation burden, leading to faster tumor progression and metastasis. Diagnosis involves PCR testing for HPV E6/E7 proteins, imaging techniques, and biopsy analysis. Treatments for HPV-positive OPSCC include antiviral therapies (e.g., Cidofovir), surgery, chemotherapy, and radiation, while HPV-negative OPSCC relies on chemotherapy and radiation.

HPV16 infecting an epithelial cell in the oropharyngeal cavity where viral DNA undergoes integration
(Figure representation created by the author:Siddharth Mitra)

Background

OPSCC, better known as Oropharyngeal Squamous Cell Carcinoma, is a form of cancer that forms in the epithelial cells of the oropharyngeal cavity. It is a type of head and neck cancer. This includes the roof of the tongue, the soft palate and the tonsils. OPSCC manifests itself in 2 forms, HPV-positive and HPV-negative. HPV-positive OPSCC is caused by persistent HPV infection, most commonly by serotype HPV16 through oral sex. During oral sex, microabrasions in the oropharyngeal cavity are created, allowing HPV16 viruses to infect the basal stem cells, repeated and concurrent infection will result in carcinogenesis. Whereas, HPV-negative OPSCC is OPSCC caused by the consumption of substances such as tobacco, alcohol, areca nut/betel quid, opioids, carcinogens etc. resulting in the formation of cancerous lesions in the oropharyngeal cavity.

Research Hypothesis

I hypothesize that HPV-negative OPSCC will present a worse prognosis, lower survival rates, and faster cancer development compared to HPV-positive OPSCC.

Results

Utilising OPSCC cancer genomics data analysis for conclusive analysis of the mortality of HPV-positive and HPV-negative OPSCC, I was able to evaluate my hypothesis (if it holds or is rejected).
From the total population of the publication- The mortality rate of HPV-positive OPSCC patients is 5/36 or 13.5% compared to the mortality rate of HPV-negative OPSCC patients which is 64/243 or 26.33%. Further per analysis, HPV-negative OPSCC patients usually undergo 80-140 mutations versus HPV-positive OPSCC patients who usually undergo 20-60 mutations.
Higher mutation load might give the HPV-negative patients much higher dysregulation of biology and thereby ability to survive and grow much more.
Finally, 100-month survival for HPV-positive OPSCC can be estimated to be 54.14% compared to the 100-month survival for HPV-negative OPSCC which is 19.83%.

Based on these KM plots, the 100-month survival for HPV-positive OPSCC can be estimated to be 54.14% compared to HPV-negative OPSCC which is 19.83%.

Conclusion

In conclusion, my hypothesis held true since I was able to prove that survival rates, survival duration and rate of oncogenesis in HPV-negative OPSCC is much higher than that of HPV-positive OPSCC. Additionally, although through biomedical intervention HPV-positive OPSCC patients can lead long and healthy lives, the same cannot be said about HPV-negative OPSCC, which brings to light the fact that we must now start focusing on specialized treatment for HPV-negative OPSCC to relief the world of a large percentage of deaths caused by OPSCC.