The prognostic significance of HPV-16 genome status of the lymph nodes, the integration status and p53 genotype in HPV-16 positive cervical cancer:: a long term follow up

Objective Prognostic evaluation of HPV-16 genome status of the pelvic lymph nodes, the integration status of HPV-16 and p53 codon 72 polymorphism in cervical cancer. Design Prospective cohort study. Setting Department of Gynaecological Oncology, University of Debrecen, Hungary. Sample Thirty-nine patients with HPV-16 positive cervical cancer. Methods Primary tumour specimens of 39 cervical cancer patients with HPV-16 positive primary tumour were subjected to multiplex polymerase chain reaction using HPV-16 E1/E2, E7 and p53 codon 72 allele-specific primers. Pelvic lymph nodes of the same patients were also tested for the presence of HPV-16 DNA and for its integration status using HPV-16 E7 and E1/E2 ORF specific primers, respectively. Main outcome measures Progression-free survival. Results Metastatic lymph nodes carried HPV-16 DNA more frequently than nodes with no evidence of disease (100.0% vs 35.7%, P = 0.001). Cases with HPV-16 positive nodes had higher recurrence rate than those with HPV-16 negative nodes (42.9% vs 11.1%, P = 0.009). There was no difference between cases with and without histologically proven nodal disease with regard to integration status of HPV-16 DNA in the primary tumour (integrated 90.9% vs 71.4%, episomal 9.1% vs 21.4%, mixed 0% vs 7.1%) and p53 codon 72 polymorphism (Arg/Arg 54.5% vs 67.9%, Pro/Pro 0 vs 7.1%, Arg/Pro 45.5% vs 21.4%). Conclusion Regardless of the presence of nodal metastasis, HPV-16 status of the nodes is a significant predictor of recurrent disease. HPV-16 integration status and p53 codon 72 genotype do not seem to have a bearing on disease outcome in cervical cancer with HPV-16 positive primary.