宫颈癌及癌前病变中人乳头瘤病毒16载量与整合频率的研究

OBJECTIVE: To investigate the association between viral load, genomic integration frequency of HPV 16 and cervical carcinogenesis and assess the probability that HPV 16 integration frequency may be utilized as a marker for cervical cancer. METHODS: Forty cases of HPV16 single infection were selected from 337 cervical scrape samples by PCR (polymerase chain reaction) amplification and DNA sequencing. The copy numbers of E2, E6 and β-actin were quantified to evaluate the viral load and integration status by real-time PCR. RESULTS: (1) The median number of adjusted viral load of normal group, LSIL (low-grade squamous intraepithelial lesion) group, HSIL (high-grade squamous intraepithelial lesion) group and squamous cervical cancer group were 0.11, 18.55, 44.63 and 7.6 copies per cell respectively. The viral load was higher in LSIL-HSIL group than that in normal group while lower in squamous cervical cancer group than that in HSIL group. (2) The median number of E2/E6 was 0.93 in normal group, 0.84 in precancerous group (LSIL-HSIL) and 0.64 in squamous cervical cancer group respectively. It showed a descending trend with the progression of cervical disease. (3) With the disease development, the proportion of episomal form decreased (normal group 4/5, LSIL group 4/6, HSIL group 10/16, cervical squamous cancer group 5/13) whereas that of integrated form (mixed and totally integrated) increased (normal group 1/5, LSIL group 2/6, HSIL group 6/16, cervical squamous cancer group 8/13). Both totally integrated cases were cervical squamous cancer. CONCLUSION: (1) HPV 16 viral load may not be an ideal marker to predict cervical carcinogenesis. (2) Due to a positive correlation between HPV16 genomic integration frequency and cervical neoplastic progression, HPV 16 integration frequency may be a potential marker of early diagnosis for cervical lesion progression.