Relationship between Human Papillomavirus Prevalence and DNA Damage in Cervical Cancer Population in Gansu Province, China.

OBJECTIVES: The aim of this study was to assess the possible reason of the high incidence and mortality of cervical cancer in Longnan, China. MATERIALS AND METHODS: 147 and 124 invasive squamous-cell carcinoma (SCC) samples from Longnan and different cities and districts of Gansu province were collected in the present study. All the samples were obtained from patients who underwent biopsies with colposcopy or advanced operations and were evaluated by experienced pathologists. HPV genotypes were examined with a validated HPV subtypes kit. The prevalence of HPV infection in SCC patients of China was analyzed by evidence-based medicine in the published literature. The markers of DNA damage response (DDR) - ATMpSer1981, H2AXp Ser139 (γH2AX), Chk2pThr68, and p53 - were analyzed by immunohistochemistry. RESULTS: HPV positivity, high-risk and multiple HPV positivity, and HPV58 infection were significantly higher in Longnan. Our results show that the prevalence of HPV infection in SCC patients of Longnan are consistent with the HPV prevalence in China. ATM, γH2AX, and p53 expressions in total and HPV+ samples were also higher in Longnan. CONCLUSIONS: HPV-related DDR activation may be one reason for the high incidence and mortality of Longnan cervical cancer.

HPV infection associated DNA damage correlated with cervical precancerous lesions and cancer in the highest area of cervical cancer mortality, Longnan, China.

OBJECTIVES: This study was to assess whether human papillomavirus (HPV) resulting in genetic instability is one reason for the high incidence and mortality of cervical cancer in Longnan. METHODS: Between 2012 and 2016, a total of 346 samples from Longnan were collected and divided into four groups: cervicitis group (n=57), cervical intraepithelial neoplasia I group (CIN I, n=63), CIN II/III group (n=79) and invasive squamous cell carcinoma group (SCC, n=147). HPV E6/E7 mRNA was detected by Quantivirus® HPV E6/E7 RNA 3.0 assay (bDNA). The markers of DNA damage response (DDR) - ataxia telangiectasia mutated (ATM) pSer1981, H2AX pSer139 (γH2AX), Chk2 pThr68 and P53 - were analyzed by immunohistochemistry. RESULTS: The activation of ATM, γH2AX, Chk2 and P53 was increased with increasing severity of cervical lesion. A significant difference of ATM expression in simple infection was also shown accompanied by the cervical lesion. The expression of γH2AX between HPV16+ and HPV16- specimens, γH2AX and P53 between HPV58+ and HPV58- groups had statistical significance. The expression and copy number of HPV E6/7 mRNA increases with the cervical lesion severity. A significant difference was shown for P53 expression between HPV E6/7 mRNA+ and mRNA- specimens. A close correlation with CHK2 expression for HPV E6/7 mRNA+ and HPV16 E6/7 mRNA+ specimens and γH2AX and CHK2 expression for SCC specimens was shown between low and high viral load groups. CONCLUSIONS: DDR, HPV genotypes and HPV E6/E7 oncogene expression correlated with the level of dysplasia of cervical lesions. HPV infection resulted in genetic instability may be one reason for the high incidence and mortality in Longnan.

Human papillomavirus genotypes associated with cervical precancerous lesions and cancer in the highest area of cervical cancer mortality, Longnan, China.

BACKGROUND: The mortality of cervical cancer in Longnan is as high as 39/10 million, ranking first in China. METHODS: Between 2012 to 2016, 329 samples with cervicitis, cervical intraepithelial neoplasia grade 1 to 3 (CINI to III), and invasive squamous cell carcinoma (SCC) were collected. HPV genotypes were examined with a validated kit for 23 different HPV subtypes. RESULTS: Compared to cervicitis, the HPV positivity is significantly higher in CINI, CIN II/III, and SCC (38.60%, 74.60%, 87.50% and 89.05%, P < 0.001) and the positivity is also higher in SCC compared to CINI (P < 0.01). The most frequently detected genotypes were HPV16 in cervicitis, HPV16, 58 and 52 in CINI and CIN II/III, and HPV16, 58 and 18 in SCC groups. HPV16 positivity in cervicitis, CINI, CIN II/III, and SCC patients were 45.46%, 46.81%, 60.32% and 78.69%, respectively. Compared to cervicitis and CINI, the odds ratios (OR) for SCC in HPV16 positive patients were 2.96 (95% confidence interval [CI]: 1.09-8.00, P < 0.05) and 4.20 (95% confidence interval [CI]: 2.05-8.61, P < 0.001), respectively. In addition, the multiple infections in cervicitis, CINI, CINII/III and SCC group are 9.09%, 27.66%, 26.98% and 25.41% and HPV16 + 58 was the most common combinations. CONCLUSION: These findings highlight the key role of HPV16, 58, 52 and 18 in the development of CIN and SCC in Longnan women and a fully aware of regional differences in HPV genotype distribution are tasks for cervical cancer control and prevention.

Expression of the γ-phosphorylated histone H2AX in gastric carcinoma and gastric precancerous lesions.

The histone γH2AX is a marker of activated DNA damage that is overexpressed in various cancers and corresponding precursor lesions, indicating that γH2AX is a component in oncogenic transformation. The present study aimed to determine whether the immunohistochemical expression of γH2AX is involved in the progression between superficial gastritis (n=20), atrophic gastritis (n=24) and gastric carcinoma (n=79). There was no increase in γH2AX expression between superficial and atrophic gastritis, but there was a significant increase in γH2AX expression between these two conditions and gastric carcinoma (χ2=68.712; P<0.001). The expression of γH2AX in moderately-differentiated gastric adenocarcinoma (n=49) was evidently higher compared with poorly-differentiated gastric adenocarcinoma (n=26; χ2=14.241; P<0.01). Staining for γH2AX did not reveal a significant association between the expression of the histone and patient age, depth of invasion, lymph node metastasis or the tumor-node-metastasis stage of the gastric carcinoma. Overall, the present study demonstrated that enhanced γH2AX expression may be closely associated with gastric carcinoma, but is less likely to be involved in the genesis of gastric carcinoma.