ASSOCIATION OF RELATIVE TELOMERE LENGTH AND RISK OF HIGH HUMAN PAPILLOMAVIRUS LOAD IN CERVICAL EPITHELIAL CELLS
Albosale A H, Mashkina E V
*Corresponding Author: Dr. Abbas Hadi Albosale, Genetics Department, Southern Federal University, 344090, Stachki, 194/1, Rostov-on-Don Province, Russia. E-mail: abbashammadi4@gmail.com
page: 65

DISCUSSION

Persistent high-risk human papillomavirus infection is the primary cause of cervical malignant neoplasm lesions [26]. As viral loads increase, in response to protracted exposure, the risk of epithelial cell dysplasia also increases. Thus, there is a discernible correlation between elevated viral loads and the incidence of abnormal lesions and cervical malignant neoplasms [27]. In the current study, cell samples taken from 50 participants with high HPV loads were investigated to ascertain whether telomere length could be employed as a potential diagnostic tool for women who are high-risk HPV positive. Thus, this study has enabled a comparative analysis of the relative telomere lengths in the DNA samples from cervical cell samples taken from participants with high HPV loads with those taken from participants in a control group. No significant differences were reported between participants with HPV loads of 4-5lg and those with HPV loads of >5lg. However, in both HPV load groups, the telomeres were shorter than what was observed in the control group. Thus, telomere shortening could be an initial molecular modification in advance of the development of high-risk HPV carcinogenesis [28]. The results emerging from the current study indicate that telemetric DNA undergoes shortening in cervical cell samples where the HPV load exceeds 4 lg. Early cervical tumorigenesis is characterized by either telomere dysfunction (the loss of telomere capping function) or excessive telomere erosion, both of which generate chromosomal aberrations that lead to oncogenesis [29]. Studies indicate that there is a link between substantially shortening telomeres and both the activation of the DNA damage response pathway (Chk2 phosphorylation) and an increase in cervical cell proliferation [30]. Shortened telomere length is associated with complex, nonreciprocal chromosomal translocations, genome amplification, deletion via breakage–fusion–bridge (BFB) cycles, and the development of epithelial carcinomas and other malignancies [31,32]. Marginal increases or predispositions to increase have been observed in association with viral loads that exceed 5 lg. The viral loads represent the number of infected cells and viral copies in individual cells. Thus, increased viral loads are linked to increased incidences of cervical cancer. Studies have shown that there is a rise in telomerase activity that corresponds with lesion development, ranging from low-grade squamous intraepithelial lesions (LSIL) to high-grade squamous intraepithelial lesions (HSIL), and onwards to invasive cervical cancer. This indicates that telomere length abnormalities constitute a common genetic change that transpires during the many stages in the development of malignant transformation. This correlates with dysplasia and telomerase activity. Furthermore, it increases with the progression of lesions [20,33–37]. There are several limitations to the current research project, the first of which is that the sample included no participants with either cervical cancer or histological lesions. This rendered it impossible to examine telomere alterations in lesions that were at a more advanced stage. The second major limitation pertains to the comparatively small size of the study sample, which might preclude generalization. It is necessary, therefore, to confirm the findings of this study in a larger population. In conclusion, the current study has revealed that shortened telomeres are present in cervical samples taken from participants who are HR-HPV positive and have elevated viral loads. Thus, telomere length has a potential application in future triaging, monitoring, and screening of women with high-risk HPV infections. It must be reiterated, however, that additional research with a larger sample group is needed before this hypothesis can be confirmed.



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