Distribution of HPV16 E6 295T/G and E7 647A/G variants in cervical cancer and effects on IFNκ and its pathway
Authors: Pan Zemin , Guo Binxuan , Wang Le , Zhao Xian , Zhe Xiangyi , Tuo Jing , Li Dongmei , Li Hongtao , Shao Renfu 
Published: May 2024

Objective: To investigate the distribution characteristics of
HPV16 E6 gene 295T/G and E7 gene 647A/G variants in different cervical
tissues in Xinjiang, to study the effects of these two loci on the
expression of molecules in IFNκ and its pathway, to explore the
molecular mechanism of their roles, and to analyse the relationship
between these two variants and the occurrence and development of
cervical cancer. Methods: (1) A total of 461 cervical
paraffin-embedded tissue samples were collected and tissue DNA was
extracted to detect the type of HPV infection by PCR, and the
distribution of HPV16 viral E6-T295G and E7-A647G variants in cervical
tissues was analysed by Sanger sequencing. Immunohistochemistry was used
to detect the expression of IFNκ and molecules on its pathway including
IFNκ, STAT1, IRF9, IFI27, IFI44L,OAS1 in cervical cancer and normal
cervical tissues. Results: (1) The HPV16 infection rate of
cervical paraffin-embedded tissue samples from women in Xinjiang region
was 64.0% by PCR. And the HPV16 infection rate of Uyghur was 75.7%, of
which the infection rate of Uyghur CIN1 and CIN2 with HPV16 was 60.6%,
and the infection rate of CIN3 and cervical cancer was 82.9%. The HPV16
infection rate of Han ethnic group was 54.5%, among which the infection
rate of Han ethnic group CIN1 and CIN2 of HPV16 was 34.0%, and the
infection rate of CIN3 and cervical cancer was 66.5%. (2) The variant
rate of Uyghur CIN1 patients presenting with E6-295T/G variant was
41.7%, and the variant rate of squamous cervical cancer patients
presenting with E6-295T/G variant was 43.4%. The variant rate of Han
ethnic group CIN1 patients presenting with the E6-295T/G variant was
33.3%, and the variant rate of squamous cervical cancer patients
presenting with the E6-295T/G variant was 16.1%. The variant rate of
Uyghur CIN1 patients presenting with the E7-647A/G variant was 41.7%,
and the variant rate of squamous cervical cancer patients presenting
with the E7-647A/G variant was 9.2%. The variant rate of E7-647A/G
variant was 45.8% in Han ethnic group of CIN1 patients and 50.0% in
squamous cervical cancer patients. (3) The results showed that the
expression of IFNκ, IRF9, OAS1, IFI27, and IFI44L molecules on the IFNκ
pathway was higher in normal cervical tissues uninfected with HPV than
that of CIN1 with HPV infection, and the difference was statistically
significant ( P<0.05). The expression of IFNκ, STAT1,
IRF9, OAS1, IFI27, IFI44L molecules in CIN3, moderately differentiated,
poorly differentiated cervical squamous carcinoma and adenocarcinoma
were higher than that of CIN1, and the molecular expression of IFN-κ and
its pathway in cervical squamous cell carcinoma and adenocarcinoma was
higher than that in normal tissues, and the difference was statistically
significant ( P<0.05). Conclusion: The rate of
E6-295T/G variation in cervical cancer patients infected with HPV16 in
Uyghur is higher than that in Han, while the rate of E7-647A/G variation
in cervical cancer patients infected with HPV16 in Han is higher than
that in Uyghur.