Genetic Variability in the E6, E7, and L1 Genes of Human Papillomavirus Types 16 and 18 among Women in Saudi Arabia

Abstract

Cervical cancer is the eighth most frequent cancer in Saudi Arabia, and most cases are associated with human papillomavirus (HPV) types 16 and 18. HPV-induced carcinogenesis may be associated with the intra-type variant, genetic mutation, or the continuous expression of viral oncogenes E6 and E7. Infection efficiency and virus antigenicity may be affected by changes in the L1 gene. Thus, this retrospective cohort study analyzed E6, E7, and L1 gene mutations in cervical specimens collected from Saudi women positive for HPV16 or HPV18 infection. HPV16 and HPV18 lineages in these specimens were predominantly from Europe. The L83V mutation in the E6 gene of HPV16 showed sufficient oncogenic potential for progression to cervical cancer. By contrast, the L28F mutation in the E7 gene of HPV16 was associated with a low risk of cervical cancer. Other specific HPV16 and HPV18 mutations were associated with an increased risk of cancer, cancer progression, viral load, and age. Four novel mutations, K53T, K53N, R365P, and K443N, were identified in the L1 gene of HPV16. These findings for HPV16 and HPV18 lineages and mutations in the E6, E7, and L1 genes among women in Saudi Arabia may inform the design and development of effective molecular diagnostic tests and vaccination strategies for the Saudi population.

Distribution of human papillomavirus among Vietnamese women with cervical cancer and genetic variability of HPV16

“…40 A recent study reports that T176N is part of the T-cell epitope region, while H76Y and T266A are part of the T-cell epitope region. 10 In our study, no H76Y or T266A were found, so the role of T176N in the amino acid interaction inside L1 requires further studies to elucidate. We discovered that the mutation characteristics of the L1 gene of HPV circulated in Vietnam differed greatly from Alsenae, 10 Wu, 31 Cao, 41 and Chiesa.…”

“…29 Other studies have revealed that the Q14H mutation, which is positioned at the binding interface of the E6-p53 complex, may play an essential role in binding to p53; 30 however, several other alterations, such as H24N, I27R, V31A, A61G, and D64E, do not occur as described by Alsanea. 10 It demonstrates that the HPV16 disseminated in Vietnam has particular mutations that might cause alterations in molecular interactions. Differences in the genetic mutations of HPV16 in Vietnam, as well as the effects on their structure and function, require additional investigation.…”

“…Two mutations found with a low frequency, H78Y and L83V, only appeared with a frequency of 6.9% each; this rate was much lower than the study of Alsanea (57.4%) and Wu (90.9%). 10,31 There are fewer studies investigating the impact of H78Y compared to L83V, however all studies indicate that amino acid 83 is primarily responsible for HR-HPV's high carcinogenicity. 32 The genetic mechanism for HPV carcinogenicity varies widely across variations and mutations, with the L83V and D25E mutations in the E6 gene being associated with a significant risk of cervical cancer.…”

“…L28F mutations are thought to be associated with a significantly lower risk of cervical cancer because they only affect DNA synthesis, pRb binding, and nuclear localization signaling. 10 The E7 gene plays a vital role in the early phases of the virus's life cycle, particularly in the replication and genome amplification stages. 36 Thus, providing an ideal role for the function of this tiny protein leads to evolutionary genetic restrictions in the E7 sequence.…”

“…In which certain gene mutations alter the biological function of proteins, causing infection to persist and lesions to progress to cancer. 10 Malignancy necessitates long-term viral persistence, which necessitates evasion of the body's immunological responses and clearance. 11 HPV has several mechanisms for interfering with an effective immune response, which may contribute to the slowing or failure of HPV infection clearance.…”