A study conducted by scientists from the University of São Paulo (USP) in Brazil and the University of Chile reveals that tobacco smoking and human papillomavirus (HPV) are established risk factors for head and neck cancer. However, the study demonstrates that these two factors can interact synergistically, further elevating the risk of developing the disease. The findings have been published in the International Journal of Molecular Sciences.
The research sheds light on the molecular mechanisms involved in head and neck cancer, providing valuable insights for the development of innovative prevention and treatment strategies, as well as other interventions that can benefit patients.
Head and neck cancer encompasses various types of cancer affecting the mouth, nose, sinuses, tonsils, throat, and thyroid. In 2020, it affected approximately 830,000 individuals worldwide, causing more than 50% of them to succumb to the disease. In Brazil alone, it led to nearly 21,000 deaths in 2019, as reported by the National Cancer Institute (INCA). Traditionally, alcohol consumption, tobacco use, and poor oral hygiene have been the primary causes of this type of cancer. However, in recent decades, HPV has emerged as a significant risk factor, particularly among younger individuals and relatively affluent patients. Head and neck cancer associated with HPV is now one of the fastest-growing types of cancer worldwide.
Enrique Boccardo, a professor in the Department of Microbiology at the University of São Paulo’s Biomedical Sciences Institute (ICB-USP) and the penultimate author of the published article, stated, “Instead of continuing to analyze smoking and HPV as oncogenic factors separately, we set out to focus on their possible interaction.”
The researchers discovered that both smoking and HPV contribute to increased oxidative stress and DNA damage, which are known factors in the development of cancer. Previous research indicates that they can regulate superoxide dismutase 2 (SOD2), a potential biomarker for oral cancer malignancy and other HPV-related diseases. In the initial stage of the study, the scientists conducted in vitro experiments using oral cells expressing the HPV16 E6 and E7 oncoproteins, indicating HPV infection. These cells were exposed to cigarette smoke condensate. The results showed a significant increase in SOD2 levels and DNA damage compared to the control group, demonstrating a detrimental interaction between HPV and cigarette smoke. The control cells expressed lower levels of SOD2 than the cells expressing E6 and E7 or those exposed to cigarette smoke. Interestingly, the cells expressing the oncoproteins and exposed to cigarette smoke exhibited even higher SOD2 levels, highlighting the interaction between HPV genes and cigarette smoke.
In the second phase of the project, supported by FAPESP (grants number 2010/20002-0 and 2019/26065-8), the researchers analyzed genomic data from 613 samples in The Cancer Genome Atlas (TCGA), a public repository containing genetic mutations associated with cancer. They specifically focused on analyzing SOD2 transcriptions to confirm their initial findings.
Boccardo emphasized the significance of the study, saying, “Although in vitro studies take place in an artificial environment, they’re a starting point for an understanding of what happens in more complex models and could enable us in the future to intervene objectively with some benefit.” He suggested that expanding the age group eligible for HPV vaccination could be considered to prevent diseases in other anatomical regions, as the current vaccination is limited to children aged 9-14 due to evidence of its effectiveness against genital pathologies.
The study successfully bridges the gap between laboratory research and clinical analysis by utilizing databases of human samples, which include RNA and protein expression analysis, as well as long-term data collection.
** Taking lead from News Medical Life Sciences
