Investigating the role of neurotransmitter system and neurotrophic factor-related genes in human papillomavirus-associated cervical lesions

Human papillomavirus (HPV) infection plays a crucial role in cervical carcinogenesis. The link between the autonomic nervous system and tumor biology is increasingly being recognized. Understanding how neural signaling pathways interact with HPV oncogenesis could open new avenues for therapeutic intervention. We aim to study the contribution of the autonomic nervous system-related genes to the HPV-associated cervical lesions. A population of 140 HPV-infected women presenting cervical lesions was compared to a control population. Genes/variants under study were: BDNF/rs6265, NTRK2/rs2289656, NGF/rs6330, SLC6A4/5-HTT variable number tandem repeats intron 2, HTR2A/rs6313, ADRBR2/rs1042713, and CHRNA5/rs16969968. Samples were genotyped using polymerase chain reaction (PCR), PCR-restriction fragment length polymorphism, and endpoint genotyping. Statistical analysis revealed a genetic contribution for SCL6A4, ADRB2, and CHRNA5. SCL6A4 showed statistically significant association in the codominant (p=0.003) and dominant models (p=0.024, odds ratio [OR] = 2.301). ADRB2 showed statistically significant association in the codominant (p<0.001), dominant (p=0.024, OR = 4.728), recessive (p<0.001, OR = 4.856), and allelic models (p<0.001, OR = 4.091), while CHRNA5 showed statistically significant association in the dominant model (p=0.030, OR = 0.529). We conclude that there is a genetic contribution of the adrenergic (ADRB2), cholinergic (CHRNA5), and serotonergic (SLC6A4) systems to cervical lesions associated with HPV infections.