Abstract

BackgroundCervical cancer incidence is low in Saudi Arabian women, suggesting low prevalence to HPV infection due to environmental, cultural and genetic differences. Therefore, we investigated HPV prevalence and genotype distribution in cervical cancer as well as the association with 9 genetic single nucleotide polymorphisms (SNPs): CDKN1A (p21) C31A, TP53 C72G, ATM G1853A, HDM2 promoter T309G, HDM2 A110G, LIG4 A591G, XRCC1 G399A, XRCC3 C241T and TGFβ1 T10C, presumed to predispose to cancer.MethodsOne hundred cervical cancer patients (90 squamous cell carcinoma and 10 adenocarcinoma) and 100 age/sex-matched controls were enrolled. SNPs were genotyped by direct sequencing and HPV was detected and typed in tumors using the HPV Linear Array Test.ResultsEighty-two cases (82%) were positive for HPV sequences. Seven HPV genotypes were present as single infections (16, 18, 31, 45, 56, 59, 73) and five double infections (16/18, 16/39, 16/70, 35/52, 45/59) were detected. Most common genotypes were HPV-16 (71%), 31 (7%), and 18, 45, 73 (4% each). Only XRCC1 SNP was significantly associated with cervical cancer (P=0.02, OD=1.69; 95% CI= 1.06–2.66). However, nested analysis revealed a preponderance of HPV-positivity in patients harboring the presumed risk allele TP53 G (P=0.06). Both XRCC1 and TP53 SNPs tended to deviate from Hardy-Weinberg equilibrium (HWE; P=0.03-0.07).ConclusionsHPV prevalence (82%) in cervical cancer is at the lower range of the worldwide estimation (85 - 99%). While XRCC1 G399A was significantly associated with cervical cancer, TP53 G72C showed borderline association only in HPV-positive patients. Deviation from HWE in HPV-positive patients indicates co-selection, hence implicating the combination of HPV and SNPs in cancer predisposition. Thus, SNPs could be more relevant biomarkers of susceptibility to cervical cancer when associated with HPV infection.

Highlights

  • Cervical cancer incidence is low in Saudi Arabian women, suggesting low prevalence to human papillomavirus (HPV) infection due to environmental, cultural and genetic differences

  • Among all the known risk factors, human papillomavirus (HPV) stands as a main cause, and high-risk HPV infections play a major role in the pathogenesis of cervical cancer with an estimated prevalence between 85% to 99% [3,4,5,6,7]

  • Study population One hundred patients with histopathologically proven, locally advanced, cervical cancer were enrolled in this study out of 218 patients followed at King Faisal Specialist Hospital and Research Centre (KFSHRC) from 2009 to FA Complex: AC D E F G

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Summary

Introduction

Cervical cancer incidence is low in Saudi Arabian women, suggesting low prevalence to HPV infection due to environmental, cultural and genetic differences. This is due to the lack of proper screening program that has helped reducing cervical cancer incidence and mortality rates by 70% in developed countries [8,9]. In contrast to the global view, the incidence of cervical cancer is very low in Saudi Arabia, ranking number 11 between all cancers in females and accounts only for 2.4% of all new cases [10], despite the lack of national screening programs. The prevalence of HPV infection among women and its association with cervical cancer in Saudi Arabia and in similar socio-cultural societies is scanty [14,16,17,18,19,20]. Early reports are discordant [22,23], that some show high incidence, such as in Indonesia, where cervical cancer ranks number 3 after breast and colorectal tumors [2]

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