Can a marker linked to cervical lesion severity also predict whether high-risk HPV will clear after treatment?

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Increased angiogenesis—the formation of blood vessels—leads to invasion in cervical cancer. Vascular endothelial growth factors (VEGFs) are involved in angiogenesis, but their molecular links to human papillomavirus (HPV), the most important causal agent, needed clarification.

This observational study used archival samples from 150 squamous cell carcinomas (SCCs) and 152 cervical intraepithelial neoplasia (CIN) lesions. Researchers examined VEGF-C using immunohistochemistry with an anti-VEGF-C antibody and tested for HPV using polymerase chain reaction (PCR). Follow-up data were available for all SCC cases, and 67 CIN lesions were monitored with serial PCR to assess HPV clearance or persistence after treatment.

High-risk (HR) HPV types were closely associated with CIN (odds ratio [OR], 19.12; 95% confidence interval [CI], 2.31 to 157.81) and SCC (OR, 27.25; 95% CI, 3.28 to 226.09). VEGF-C expression increased linearly: it was weak in CIN1 and intense in CIN3 and SCC (OR, 20.49; 95% CI, 8.69 to 48.26).

Increased VEGF-C expression was a sensitive marker of HR-HPV type, with a sensitivity of 93.5% (95% CI, 90.1% to 96.9%) and an OR of 4.70 (95% CI, 2.17 to 10.21). However, it lost statistical significance in multivariate regression; p16(INK4a) and survivin were equally strong independent predictors of HR-HPV.

Abnormal VEGF-C expression did not predict HR-HPV clearance or persistence after CIN treatment. In cervical cancer, VEGF-C had no prognostic value in either univariate or multivariate survival analysis. After adjustment for HR-HPV, FIGO stage, age, and tumour grade, only FIGO stage and age remained independent prognostic predictors.

The authors concluded that VEGF-C is an early marker of cervical carcinogenesis, with expression increasing linearly from low-grade CIN onward. VEGF-C expression was closely related to HR-HPV in cervical lesions. The authors suggested that this was probably because the E6 oncoprotein of HR-HPV increases VEGF-C expression independently of p53.