No Genetically Predicted Association Between Human Papillomavirus and COVID-19: A Mendelian Randomization Analysis in European Ancestry Population

Purpose: Previous studies reveal that coronavirus disease 2019 (COVID-19) infection accelerates the progression of Human papillomavirus (HPV)-related diseases, but the results remain controversial. We conducted a bidirectional two-sample Mendelian randomization (MR) study to evaluate the causal association between HPV infection and COVID-19 using genome-wide association study (GWAS) summary data from European ancestry populations. Patients and Methods: Genetic summary data of HPV infection and COVID-19 were derived from the public GWAS meta-analysis and the COVID-19 host genetics initiative GWAS, respectively. The causal link between HPV infection and COVID-19 was evaluated by MR analysis with inverse variance weighting (IVW), MR-Egger, and weighted median methods. Additional MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) and MR-Egger regression methods were used to identify the potential pleiotropy of the instrumental variables (IVs). Bonferroni correction was used to account for the issue of multiple comparisons, leading to a statistically significant P -value of less than 0.004 (0.05/2*3*2). Results: There were no significantly causal links of HPV-16 or HPV-18 infection with COVID-19 infection, hospitalized COVID-19, or severe COVID-19 (all P > 0.05). Furthermore, no significant causal effect of all three types of COVID-19 on HPV-16 and HPV-18 was observed in the reverse MR analyses (all P > 0.05). MR-Egger regression and MR-PRESSO global test did not find the presence of horizontal pleiotropy between IVs of HPV infection and COVID-19. Conclusion: This study shows that COVID-19 infection does not affect the risk of HPV-16/18 infection, nor does HPV-16/18 infection increase COVID-19 infection risk. It highlights the need to maintain routine health management and no change to HPV prevention strategies. Keywords: HPV, COVID-19, mendelian randomization, causal relationship, genetic association