Detection of human papillomavirus types 16 and 18 mRNA in peripheral bloodof advanced cervical cancer patients and its association with prognosis

Purpose: To evaluate the feasibility of detecting human papillomavirus E6 ( HPVE6) gene mRNA in the peripheral blood of patients with locally advanced cervical cancer, and the relationship of the circulating HPV viral-specific mRNA with clinicopathologic factors and prognosis of locally advanced cerv ical cancer. Patients and Methods: The presence of types 16 and 18 HPVE6 gene mRNA was d etermined by reverse transcription followed by nested polymerase chain reac tion. Thirty-five patients with locally advanced cervical cancer who were p ositive for HPV type 16 or 18 DNA were included in the study. All patients received external-beam radiation therapy followed by intracavitary brachyth erapy. Results: Eighteen (51.4%) of 35 HPV DNA-positive cervical cancer patients h ad HPV-specific mRNA in their peripheral blood cells, compared with none of 17 HPV DNA-negative cervical cancer patients and none of 12 control volunt eers, The presence of HPVE6 gene mRNA in peripheral blood was associated wi th bulky tumor volume (> 4 cm) and pelvic lymph node metastasis (tumor volu me, P =.03; lymph node status, P =.03). After a median follow-up of 22 mont hs, patients who were positive for peripheral-blood HPVE6 gene mRNA had a s ignificantly higher risk of recurrence than those who were negative (10 of 18 v three of 17, P =.02; mean recurrent time, 20.7 months v 12.6 months, P =.02), There was also a statistically significant association of periphera l-blood HPVE6 gene mRNA positivity with distant metastasis (eight of 18 van e of 17; P =.01). Conclusion: Results of this study seem to suggest that the presence of HPVE 6 gene mRNA in peripheral blood may provide an early marker that identifies patients who are at risk for metastasis. J Clin Oncol 17:1391-1396. (C) 19 99 by American Society of Clinical Oncology.