Dna Damage Level Correlates With Grade Of Cervical Dysplasia: A Potential Biomarker To Assess Cervical Cancer Risk.

Abstract Background: In 2018, cervical cancer (CC) accounted for 311,000 deaths worldwide. Nearly all CC are linked to human papillomavirus (HPV) infection. HPV infection is nearly ubiquitous, but persistent infection can lead to dysplasia and ultimately cancer. Cervical dysplasia is classified into low (CIN1), moderate (CIN2), and high (CIN3) cervical intraepithelial neoplasia. CIN2 and CIN3 are considered premalignant lesions, with about 5-12% progressing to CC. However, it is unclear which of these high-risk CIN2/3 patients will go on to develop CC. Chronic HPV infection increases DNA damage and reduces DNA repair. Using a novel, highly sensitive, DNA damage detection assay (q-PADDA) developed in our lab, we have recently shown that nuclear DNA (nDNA) damage is a potential tool to predict oropharyngeal cancer risk, another HPV infection associated malignancy. Herein, we hypothesized that nDNA damage could also be used as a tool to screen for high CC risk. Aims: (1) To measure the amount of nDNA damage in cervical samples with distinct pathologies. (2) To determine whether the number of DNA lesions correlates with the grade of cervical dysplasia. Methods: A total of 105 participants were enrolled in the study. Cervical samples were collected using a cytobrush during pelvic examination. Total genomic DNA was extracted, and nDNA damage was quantified using q-PADDA. Demographic, clinicopathologic, and risk factor data were collected from detailed questionnaires and medical charts. Data were subjected to ANOVA and regression analysis using SAS software. Results: Histopathological analysis revealed that 33 samples had no dysplasia (CIN0), 30 samples were CIN1, 37 samples were CIN2/3, and five samples were CC. DNA damage analysis has been completed in 26 samples. We observed that CIN1 cases had a 2-fold (p<0.05), and CIN2/3 cases had a three-fold (p≤0.02) increase in the number of nDNA lesions when compared to CIN0. No significant correlation was observed between age, race, smoking and alcohol status and final pathology per regression analysis. Conclusion: Our preliminary analysis reveals that the amount of DNA damage is the lowest in patients without cervical dysplasia and increases progressively with the grade of dysplasia and corresponding CC risk. This promising data supports the use of DNA damage as biomarker of cervical cancer risk. The remainder of this data will be analyzed, but more extensive population studies are warranted to fully assess the potential of this approach to predict CC risk. Grant support: This work was supported by OSCTR/NIH IDeA Program and The Peggy and Charles Stephenson Cancer Center. Dr. Queimado holds a PHF Endowed Chair in Otorhinolaryngology. Citation Format: Balaji Sadhasivam, Camille C. Jackson, Katie M. Smith, Tristan Coles, Isha Jhingan, Rebekah Stewart, Elizabeth H. Hahn, Sarah E. Johnston, Daniel Y. Zhao, Vengatesh Ganapathy, Lurdes Queimado. DNA damage level correlates with grade of cervical dysplasia: a potential biomarker to assess cervical cancer risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2547.