Introduction: Cervical cancer is the fourth common cancer in women worldwide. In most cases, the disease is induced by persistent high-risk human papillomavirus (HPV) infection. This study aimed to assess the role of cytokeratin 7 (CK7) and cytokeratin 19 (CK19) in HPV-induced cervical epithelial lesions using tissue microarray (TMA). Methods: A retrospective cohort study included females with cervical low-grade intraepithelial lesion (LSIL), high-grade intraepithelial lesion (HSIL), and squamous cell carcinoma (SCC). TMA was constructed using specimens of 270 cases and 233 control tissues. CK7 and CK19 immunohistochemistry was scored as negative or positive. Follow-up information was gathered. Results: CK7 was negative in about 85% of LSILs and positive in 55% of HSILs (p < 0.001). CK19 showed positivity in about 50% of LSILs and 77% of the HSILs (p < 0.001). For cases with available follow-up data, about 69% of CK7-positive LSILs progressed to higher grade lesions and 64% of CK7-positive HSILs showed progression to higher grades (CIN2 to CIN3) or to SCC. Regarding CK19, nearly 66% positive LSILs progressed to HSIL whereas, 62% of positive HSILs showed progression. LSILs with positivity for both markers progressed to HSIL in 70% of cases. Conclusion: CK7 and CK19 positivity are significantly associated with higher grade HPV-induced cervical lesions. Lesions with combined CK7 and CK19 positivity have a higher risk of progression to higher grade lesions.

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