Reduced rate of human papillomavirus infection and genetic overtransmission of TP53 72C polymorphic variant lower cervical cancer incidence

BACKGROUND Cervical cancer is a predominantly human papillomavirus (HPV)‐driven disease worldwide. However, its incidence is unexplainably low in western Asia, including Saudi Arabia. Using this paradigm, we investigated the role of HPV infection rate and host genetic predisposition in TP53 G72C single nucleotide polymorphism (SNP) presumed to affect cancer incidence. METHODS Patients treated between 1990 and 2012 were reviewed, and a series of 232 invasive cervical cancer cases were studied and compared with 313 matched controls without cancer. SNP was genotyped by way of direct sequencing. HPV linear array analysis was used to detect and genotype HPV in tumor samples. RESULTS The incidence of cervical cancer revealed bimodal peaks at 42.5 years, with a slighter rebound at 60.8 years. Among all cases, 77% were HPV‐positive and 16 HPV genotypes were detected—mostly genotypes 16 (75%) and 18 (9%)—with no difference by age, histology, or geographical region. Although the TP53 G72C genotype was not associated with overall cervical cancer risk, it was significantly associated with HPV positivity (odds ratio, 0.57; 95% confidence interval, 0.36‐0.90; P = .016). Furthermore, the variant C allele was significantly overtransmitted in the population (P