Simultaneous Effects of Viral Factors of Human Papilloma Virus and Epstein-Barr Virus on Progression of Breast and Thyroid Cancers: Application of Structural Equation Modeling

This study aimed to assess effects of the sets of EBV and HPV expressed proteins simultaneously on the sets of cellular/inflammatory factors in breast and thyroid cancers using structural equation modeling. In this multi-center case-control study, according to the inclusion and exclusion criteria, 83 breast and 57 thyroid specimens were collected from the eligible patients. In addition, 31 and 18 histopathological evaluated normal breast and thyroid samples were also examined as age-matched healthy controls. In addition, ELISA and Real-time PCR were used to measure the expression level of viral and cellular/inflammatory genes and proteins. Structural equation modeling was used to test the causal associations between the sets of EBV and HPV expressed proteins with inflammatory factors in breast and thyroid cancers development. Breast cancer patients had a higher incidence of HPV-positively and EBV-positively than healthy controls (OR=1.66, 95%CI=0.79-3.47, P-value=0.177), (OR=3.18, 95%CI=1.52-6.63, P-value=0.002), respectively. In addition, thyroid cancer patients had a significantly higher incidence of EBV-positivity than healthy controls (OR=3.72, 95% CI=1.65-8.36, P-value=0.001). After fitting the SEM model, HPV proteins factor has significant direct and total effects on the cellular/inflammatory factors in breast cancer (direct effect: β=0.426, P-value=0.01; total effect: β=0.549, P-value<0.001). However, EBV proteins factor has most significant total effect on the cellular/inflammatory factors in breast cancer (total effect: β=0.804, P-value<0.001) than the cellular/inflammatory factors in thyroid cancer (total effect: β=0.789, P-value<0.001). For the first time, a significant association between EBV and HPV -genes, anoikis resistance and the development of breast and thyroid cancers demonstrated by using SEM, Simultaneously.