Involvement Of HPV Infection In Cervical And Head & Neck Cancers And Its Association With Genetic Predisposition In Saudi Arabia

Ghazi ALSBEIH, King Faisal Specialist Hospital & Research Centre, Saudi Arabia
AL-HARBI N. 1 , BIN JUDIA S. 1 , ELEWISY S. 1 , CASTRO J. 1 , AL-QARNI A. 2 , AL-QAHTANI W. 2 , MISHRA K. 1 , HAMED S. 2 , EL-SEBAIE M. 3 , ALMANEA H. 4 , KHOJA H. 4 , TULBAH A. 4 , ALRAJHI N. 3

1 Biomedical Physics, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
2 College of Science, King Saud University, Riyadh, Saudi Arabia
3 Radiation Oncology, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
4 Pathology and Laboratory Medicine, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia

Purpose: Human papillomavirus (HPV) is implicated in several carcinomas including cervix uterine, anogenital and subgroup of oropharyngeal cancers. We studied the extent of HPV involvement in these cancers and the association with genetic single nucleotide polymorphisms (SNPs), presumed to predispose to cancer. The aim is to provide health authorities with guidelines for prevention.
Methods: 213 cervix and 200 oropharyngeal cancers were included. HPV detection and genotyping were carried out using HPV Linear Array, which enables the detection of 37 most common high- and low-risk HPV genotypes. Genetic polymorphisms were compared with 300 normal volunteers with no history of cancer (controls). SNPs in 9 candidate genes (CDKN1A (p21) C31A, TP53 C72G, ATM G1853A, HDM2 promoter T309G, HDM2 A110G, DNA Ligase IV A591G, XRCC1 G399A, XRCC3 C241T and TGFβ1 T10C) were genotyped by direct sequencing.
Results: HPV was detected in 160 cervix and 4 oropharyngeal cancer patients (75% and 2%; respectively). Seven different single HPV genotypes (16, 18, 31, 45, 56, 59, 73) and 5 double infections (16/18, 16/39, 16/70, 35/52, 45/59) were detected. The most common genotype was HPV-16 (71%), followed by 31 (7%), and 18, 45, 73 (4% each). Cancer predisposition (n=100) showed significant association for XRCC1 (P=0.02, OR=1.69; 95%CI=1.06–2.66). More interestingly, nested analysis revealed a preponderance of HPV-positivity in patients harboring the TP53 codon 72 risk allele G with a borderline significant association (P = 0.06), and deviation from Hardy-Weinberg equilibrium (P = 0.07).
Conclusions: The rate of HPV infection was lower than estimated worldwide. HPV 16 and 18 were the most common genotypes. Current HPV vaccines could protect two-third of cervical cancer in Saudi Arabia. Genetic predisposition suggest that HPV-associated cancer occurrence is not random in the population and that certain genetic SNPs favors its development.
Funding: Supported by NSTIP-KACST Grant#12-MED2945-20 (RAC#2130025).