Increased HPV L1 gene methylation and multiple infection status lead to the difference of cervical epithelial cell lesion in different ethnic women of Xinjiang, China

Abstract

Human papillomavirus (HPV) L1 gene methylation deeply involved in the progression and heterogeneity of cervical cell epithelial lesions. The DNA ploidy also represented the early lesions of cervical cell, and it was associated with different HPV infection status in different ethnic women. So, the research was to explore whether it was possible that HPV L1 gene methylation and HPV infection status as the risk factors to lead to the differences of cervical epithelial cells’ lesions in different ethnics women.The flow-through hybridization and gene chip for HPV genotypes test, general characteristics, and cervical exfoliated cell samples were collected from 94 Uygur and 79 Han women with HPV-16 infection. The cases were divided into the single HPV-16 (sHPV-16) infection group and multiple HPV-16 (mHPV-16) infection group in each ethnic women. The DNA ploidy was analyzed by flow cytometry, and the methylation-sensitive high resolution melting (MS-HRM) was used to test the HPV-16 L1 gene methylation, the results of methylation was segmented into mild methylation, moderate methylation, and severe methylation groups. Multifactor logistic analysis explored the relation between DNA heteroploid and HPV-16 infection status, HPV-16 L1 gene methylation in different ethnic women.The higher proportion of mHPV-16 infection in Uygur than Han women (61.7% vs 38.0%). L1 gene methylation had statistic difference between single and mHPV-16 infection under the same ethnic women. The proportion of DNA heteroploid had statistic difference between different HPV-16 infection status or different L1 gene methylation grades in Han or Uygur women. Both L1 gene methylation and HPV infection status were the risk factors of DNA heteroploid. Compared to the sHPV-16 infection, the odds ratio (OR) of mHPV-16 infection were 4.409 (CI: 1.398–13.910) and 3.279 (CI: 1.069–10.060) in Han and Uygur women. Compared the mild L1 gene methylation, the OR of moderate L1 gene methylation were 3.313 (CI: 1.002–10.952) and 5.075 (CI: 1.385–18.603) in Han and Uygur women, the OR of severe L1 gene methylation were 20.592 (CI: 3.691–114.880) and 63.634 (CI: 10.400–389.368) in Han and Uygur women.The study first reported that HPV L1 gene methylation and HPV infection status were the risk factors to the DNA heteroploid of cervical cell in different ethnics women, HPV L1 gene methylation and infection status should be recommended to the existing system of cervical lesion screening in order to provide better serves for the HPV infected women, especially for the ethnic women with high proportion of severe L1 gene methylation and multiple infection status.

Risks of female genital tract related cancers (gynecological cancers) or breast cancer in women with and without chronic kidney disease

“…One study suggested that routine cancer screening in the population with CKD is a relatively inefficient allocation of financial resources, because the net gain in life expectancy from a typical cancer screening program was calculated to be 5 days or less and the gain of survival could be obtained via a reduction of 0.02% or less in the baseline CKD-related mortality rate. [ 42 , 43 ] In the current study, we did not find the increased risk of GC in the younger group (Table 4 ). By contrast, we found that the GC risk was similar in these younger women (< 40 years), regardless of women with or without CKD.…”

“…In addition, these CKD women subsequently may have a prolonged latency of HPV infection or persistent HPV infection, which is a key factor for the development of cervical pre-cancer lesions and cancers in women. [ 40 – 42 ] Furthermore, some studies showed that the CKD women were substantially less likely to undergo cervical cancer screening compared with women without CKD. [ 21 , 22 ] Both provided a good reason to explain the finding of an increased risk of cervical cancer in the CKD women with CKD.…”

Genome-Wide Profiling of Human Papillomavirus DNA Integration into Human Genome and Its Influence on PD-L1 Expression in Chinese Uygur Cervical Cancer Women

“…Cervical cancer was one of the most common malignant tumors in China, in which its prevalence rate was 7th in all cancers and its mortality was 8th in all female cancers [1]. HPV infection is known as the main cause of cervical cancer; most of HPV infection could be cleaned by the host immune responses, but some persistent HPV infection would lead to the cytopathy of cervical cancer cells [2][3][4]. The previous studies found that the HPV persistent infection consisted of two phases: in the first phase of viral replication, HPV firstly infected basal cells of the cervix, bare virus DNA was the free state in the host cell nucleus.…”

Searching HPV genome for methylation sites involved in molecular progression to cervical precancer

“…One of the epigenetic mechanisms that are increasingly studied is HPV genes' methylation. At present, a consistent correlation of increased methylation of capsid viral genes with histology severity is referred by the researchers 7, 9, 11, 19, 20. On the other hand, studies on methylation status of the UTR , E6 and E7 regions reveal heterogeneous and rather inconclusive results 21-25.…”