Differential Expression of HPV16/18 E6 in Gynecological Cancers and its Association with MMP-2 Expression
DOI:
https://doi.org/10.32350/bsr.82.07Keywords:
Human papillomavirus 16, endometrial and ovarian cancers, Matrix Metalloproteinase 2 (MMP2), uterine cervical neoplasmsAbstract
Background. Human Papillomavirus (HPV) is the most common sexually transmitted infection, worldwide. High-risk HPV 16 and 18 remain significant factors in the development of HPV-related malignancies. In Pakistan, where HPV screening and vaccination programs are not yet widespread, exploring HPV prevalence in gynecological cancers is essential. Matrix metalloproteinase-2 (MMP-2) is an enzyme responsible for extracellular matrix degradation and contributes to tumor invasion and metastasis. This study aimed to investigate the prevalence of HPV16/18’s oncoprotein E6 expression in gynecological malignancies and its relationship with MMP-2.
Methods. The study cohort included formalin-fixed paraffin embedded (FFPE) tissue biopsies from patients with cervical cancer (n= 29), ovarian cancer (n= 16), and endometrial cancer (n= 16). Immunohistochemistry was performed to evaluate the expression levels of HPV16/18 E6 and MMP-2. Protein-protein interaction was investigated using PEPPI and INTAct tools.
Results. The study found HPV16/18 E6 expression in 93% of cervical cancer cases, as compared to 12% ovarian and 18% endometrial cancer cases. This difference in expression across tissues is highly significant (p<0.0001), emphasizing the strong association of E6 expression with cervical cancer. A strong correlation was also observed between E6 and MMP-2 (p=0.001). When analyzed separately, only MMP-2 expression significantly predicted malignancy (p=0.025); however, their co-expression demonstrated a stronger association with malignant phenotype (p=0.008). Interestingly, protein-protein interaction analysis suggested that E6 does not directly bind to MMP-2 but may instead act through a broader interaction network, indirectly driving disease progression.
Conclusion. HPV E6 expression has a strong association with MMP-2 and their co-expression serves as a significant predictor of malignancy.
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Copyright (c) 2026 Sabreen Abdul Qayyum, Shagufta Maroof, Sobia Tabassum, Aamna Dilshad, Huma Saifullah, Ammad Aslam Khan, Naureen Ehsan Ilahi
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