Expression Of E6 Oncoprotein And Incidence Of High Cervical Precancerous Lesions Among HPV Infected Women: 5 Year Follow Up Results In A Chinese Cohort

Qian ZHANG, Cancer Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, China
HU S. 1 , CHEN F. 1 , ZHANG X. 2 , PAN Q. 3 , MA J. 4 , SHI S. 4 , ZHAO F. 1

1 Department of Cancer Epidemiology,Cancer Institute, Chinese Academy of Medical Sciences and Peking Union Medical College
2 Department of Pathology,Cancer Institute, Chinese Academy of Medical Sciences and Peking Union Medical College
3 Department of Cytopathology,Cancer Institute, Chinese Academy of Medical Sciences and Peking Union Medical College
4 Xiangyuan women and children's Hospital

Purpose: To evaluate the correlation of expression of E6 oncoprotein and incidence of the cervical precancerous lesions caused by HR-HPV infection in 5 years among a Chinese rural screening cohort.
Methods: The screening cohort with 1997 women aged 35-45 was built in 1999 and followed up in 15 years by cytology and HR-HPV testing every 5 years. The expression of E6 oncoprotein and incidence of the cervical precancerous lesions with CIN2+ were analyzed in the year of 2005 and 2014. The risk of CIN2+ incidence and E6 expression were estimated by HPV infection status and times of HPV positive testing.
Results: The positive rates of HPV, E6 oncoprotein and CIN2+ of the followed population were 17.6%, 1.3% and 1.3% respectively. A significant higher expression of E6 oncoprotein after 5 years was observed in HR-HPV positive women than in the women with HR-HPV negative (4.2% vs. 0.6%, RR=6.7, 95%CI: 3.4-13.2). The incidence risk of CIN2+ in HR-HPV positive women after 5 years was significantly higher than that of women with HR-HPV negative (5.9% vs. 0.3%, RR=21.9, 95%CI: 9.1-52.5). Compared to HPV negative women, the incidences of CIN2+ were higher in women with once HPV positivity (RR=6.8) and in women with twice HPV positivity (RR=92.3) in 5 years. When stratified by E6 oncoprotein expression, the incidence risk of CIN2+ in women with twice HPV positivity and E6 positive expression were 228.7 times higher than that of women with double negative in HPV and E6 oncoprotein (95%CI: 63.7-821.4).
Conclusions: Our data indicate multiple times of HPV infected events and expression of E6 oncoprotein elevate the risk of CIN2+ development. HPV infection history and E6 oncoprotein  could assist the triage of HPV positive women in cervical screening.
Funding source: Our work was supported by the National Natural Science of Foundation of China (No 81322040).