Journal of Clinical Oncology, Vol 15, 1008-1012, Copyright © 1997 by American Society of Clinical Oncology
Detection of human papillomavirus mRNA and cervical cancer cells in peripheral blood of cervical cancer patients with metastasis
CC Pao, JJ Hor, FP Yang, CY Lin and CJ Tseng
Department of Biochemistry, Chang Gung College of Medicine and Technology, Taipei, Taiwan. ccpao@cguaplo.cgu.edu.tw
PURPOSE: To determine the presence of cervical cancer cells in circulating
peripheral blood of stage IVb cervical cancer patients with metastasis to
distant organs. PATIENTS AND METHODS: Cervical cancer tissue from 15 stage
IVb cervical cancer patients with metastasis were analyzed for the presence
of human papillomavirus (HPV) type 16 DNA by nested polymerase chain
reaction (PCR). The presence of transcriptional products of the HPV type 16
E6-transforming gene in the peripheral blood of the same 15 cancer patients
was analyzed by reverse transcription and PCR. Cervical tissues and
peripheral-blood specimens from 12 normal healthy individuals served as
controls. RESULTS: Thirteen of 15 (86.7%) cervical cancer tissues from same
number of patients were found to contain HPV type 16 DNA. Peripheral-blood
specimens from 12 of 13 (92.3%) cervical HPV DNA-positive patients were
found to contain HPV-specific mRNA detectable by reverse transcription (RT)
and PCR. Cervical tissues from all 12 normal controls were HPV- free. None
of the peripheral-blood specimens from two cervical HPV- negative cancer
patients and 12 normal controls contained detectable amounts of mRNA of HPV
type 16 E6-transforming gene. CONCLUSION: The most likely source of the
HPV-specific mRNA detected in the peripheral blood of cervical cancer
patients with metastasis is the cervical cancer cells derived from or shed
from the cervix. The presence of HPV E6 mRNAs in peripheral blood may be a
sensitive indicator of circulating cervical cancer cells. If PCR positivity
is proven to be able to predict disease progression reliably, these
findings may have clinical applications in the treatment of cervical and
many other cancers.