Variable Expression of Oncogene-Induced Senescence/SASP Surrogates in HPV-Associated Precancerous Cervical Tissue

Oncogene-induced senescence (OIS) is a form of cellular senescence triggered by oncogenic signaling and, potentially, by infection with oncogenic viruses. The role of senescence, along with its associated secretory phenotype, in the development of cervical cancer remains unclear. Additionally, the expression of the senescence-associated secretory phenotype (SASP) has not yet been explored in cervical premalignant lesions infected by the Human Papilloma Virus (HPV). This study aimed to investigate the expression of OIS and SASP markers in HPV-infected cervical precancerous lesions. We used a set of patient-derived precancerous (n = 32) and noncancerous (chronic cervicitis; n = 10) tissue samples to investigate the gene expression of several OIS (LMNB1, CDKN2A, CDKN2B, and CDKN1A), and SASP (IL1A, CCL2, TGFB1, CXCL8, and MMP9) biomarkers using qRT-PCR. OIS status was confirmed in precancerous lesions based on Lamin B1 downregulation by immunohistochemical staining. HPV status for all precancerous lesions was tested. Most of the noncancerous samples showed high Lamin B1 expression, however, precancerous lesions exhibited significant Lamin B1 downregulation (p < 0.001). Fifty-five percent of the precancerous samples were positive for HPV infection, with HPV-16 as the dominant genotype. Lamin B1 downregulation coincided with HPV E6 positive expression. CDKN2A and CDKN2B expression was higher in precancerous lesions compared to noncancerous tissue, while LMNB1 was downregulated. The SASP profile of premalignant lesions included elevated CXCL8 and TGFB1 and reduced IL1A, CCL2, and MMP9. this work shall provide an opportunity to further examine the role of OIS and the SASP in the process of malignant cervical transformation.