[Analysis of factors influencing radiation-induced liver injury caused by stereotactic radiotherapy in patients with primary hepatocellular carcinoma].

Objective: To analyze the factors influencing radiation-induced liver injury after receiving Cyberknife stereotactic radiotherapy in patients with primary hepatocellular carcinoma. Methods: 278 cases with primary hepatocellular carcinoma from July 2016 to April 2019 were prospectively enrolled. Stereotactic radiosurgery with a prescription dose of 48-55gy/5-8 times were given. Liver function, coagulation function, Child-Pugh score, and liver imaging changes were dynamically observed before and after treatment to evaluate the occurrence of radiation-induced liver injury. Logistic regression model was used to analyze the factors influencing radiation-induced liver injury. Results: Among 278 cases, 3 cases of tumor progression were excluded, and a total of 275 cases were included for analysis. The overall survival rate after 8 months of treatment was 100%. Among them, 22 cases were diagnosed as radiation-induced liver injury, with an incidence rate of 8%, and all cases were recovered after symptomatic treatment. Multivariate analysis result suggested that the peripheral white blood cell count was factors influencing the occurrence of radiation-induced liver injury. Conclusion: Cyberknife stereotactic radiotherapy has a low incidence of radiation-induced liver injury in patients with liver cancer, and it is a relatively safe treatment method. Patients with low peripheral white blood cell counts before treatment should be closely monitored for early detection and treatment.

[Effectiveness of the thermal ablation in the treatment of human papillomavirus infection and cervical intraepithelial neoplasia in Chinese women].

Objective: To evaluate the effectiveness of thermal ablation in the treatment of human papillomavirus (HPV) infection and cervical intraepithelial neoplasia (CIN) in Chinese women. Methods: The high-risk HPV-positive women aged 20-65 who were detected through a cervical cancer screening project implemented in three rural sites (Etuoke counties in Inner Mongolia, Xiangyuan and Yangcheng counties in Shanxi Province) and one urban site (Shenzhen) in China were included in this prospective study. Follow up evaluation was performed on HPV positive women who underwent thermal ablation (n=166) as well as received no treatment (n=2 716) in cervical cancer screening program. For women with thermal ablation treatment, HPV test and cytology were used for follow-up with the interval of 6 months or longer after treatment. For women without treatment, HPV test was used for annual follow-up. Women with positive results in either of the HPV tests or abnormal cytology were referred for a colposcopy or biopsy if necessary. The HPV clearance rate and the cure rate of CIN were compared between the two groups. Results: A total of 152 women treated with thermal ablation and 2 539 women without treatment reported for follow-up evaluation with the age M(Q1, Q3) of 42 (36, 48) and 47 (41, 54) years old, and the median time to follow-up time of 23.4 (12.4, 24.5) and 23.5 (12.4, 24.0)months, respectively. The HPV clearance rate in women undergoing thermal ablation was significantly higher than that in women with no treatment (73.0% vs 46.1%, P<0.001). The HPV16, HPV52 and HPV58 clearance rates among women receiving thermal ablation were higher than that in women without treatment with the OR (95%CI) of 2.8 (1.3-6.1), 3.2 (1.3-7.9) and 5.8 (2.1-15.6). For women with histologically confirmed CIN at baseline, cure rates were 77.4%(n=72) for thermal ablation. Cure rates of the thermal ablation were 81.0%(n=47) for CIN grade one (CIN1) and 71.4% (n=25) for CIN grade two or worse (CIN2+). Conclusions: Thermal ablation is effective to clear the HPV infection as well as to treat CIN. Particularly for the HPV genotypes with the paramount attributable proportion to cervical cancer and precancerous in China, the HPV clearance rate was significantly higher than that reported in the women without treatment.

[Evaluation of the effectiveness of BMRT-HPV for cervical cancer screening].

Objective: Evaluation of the clinical value of the BioPerfectus multiplex real time (BMRT)-HPV for cervical cancer screening. Methods: Physician-collected specimens of 1 495 women who were positive of Cobas 4800 HPV (Cobas-HPV), HPV genotyping based on SEQ uencing (SEQ-HPV), and (or) cytology ≥low grade squamous intraepithelial lesion (LSIL) in the primary screening of Chinese Multiple-center Screening Trial (CHIMUST), and 2 990 women selected from those who were negative of primary screening in the same project through nested control randomization with age-matching were tested for BMRT-HPV, which reported type-specific viral loads/10 000 cells in each specimen. With comparing to Cobas-HPV results and taking cervical histopathological diagnosis as the endpoint, the concordance of high-risk (HR)-HPV subtypes among the three assays was explored ,and the sensitivity and specificity of BMRT-HPV for cervical cancer screening were evaluated. Results: (1) The overall agreenment of HR-HPV subtypes between BMRT-HPV and Cobas-HPV, or SEQ-HPV test sample was 94.8%, 94.4%, with Kappa values 0.827, 0.814. (2) The sensitivity and specificity for cervical intraepithelial neoplasia (CIN) Ⅱ+ of BMRT-HPV, Cobas-HPV and SEQ-HPV were 92.62%, 94.26%, 93.44% and 84.67%, 83.25%, 82.76%, respectively. There were no significant difference in sensitivity among the three HPV assays (all P>0.05), but the specificity of BMRT-HPV for CIN Ⅱ+ was higher than those of Cobas-HPV and SEQ-HPV (P<0.01). The sensitivity for CIN Ⅲ+ of three HPV assays were all 100.00%, and the specificity for CIN Ⅲ+ of BMRT-HPV was higher than those of Cobas-HPV and SEQ-HPV (83.40% vs 81.95%, 83.40% vs 81.50%; P<0.01). The number of pathological examinations of colposcopy for cervical biopsy detected in 1 case of CIN Ⅱ+ or CIN Ⅲ+ in BMRT-HPV was less than those in Cobas-HPV and SEQ-HPV (P<0.01). When using HPV 16/18 + cytology ≥atypical squamous cell of undetermined signification (ASCUS) to triage HPV positive women among three assays, there was no different in the sensitivities of detecting CIN Ⅱ+ and CIN Ⅲ+ (P>0.05). The specificity BMRT-HPV was slightly higher than those in Cobas-HPV or SEQ-HPV (all P<0.05), and the colposcopy referral rate was lower than those in Cobas-HPV and SEQ-HPV (all P<0.05). Conclusions: BMRT-HPV is as sensitive as Cobas-HPV or SEQ-HPV for primary cervical cancer screening, and has higher specificity. Therefore it could be used as a primary screening method for cervical cancer, which is worthy of clinical application.

[Clinical efficacy of cyberknife in patients with primary large hepatocellular carcinoma over 70 years old].

Objective: To analyze the clinical efficacy and safety of cyberknife in the treatment of patients with primary large hepatocellular carcinoma over 70 years old. Methods: A total of 82 patients (58 males and 24 females) with large hepatocellular carcinoma aged over 70 years (70 to 85 years, (75±4) years) with a median tumor diameter of 6.7 cm (5.0~10.0 cm) were retrospectively collected. All patients were diagnosed by pathology or radiography in the Cancer Radiotherapy Center of the Fifth Medical Center of the PLA General Hospital from March 2014 to December 2018, and treated with cyberknife stereotactic radiotherapy. Progression free survival rate (PFS), local control rate (LC), overall survival rate (OS) and adverse reactions were observed at 1, 2 and 3 years. Kaplan-Meier was used for survival analysis, and Cox regression model was used to analyze survival-related factors. Results: All 82 patients successfully completed radiation therapy with a median survival time of 20 months, a median PFS of 10 months, an objective response rate of 64.63% (53/82), and a disease control rate of 85.37% (70/82). After treatment, the PFS at 1, 2, and 3 years were 39.0% (32/82), 22.1% (18/82), and 17.1% (14/82), respectively; the LC at 1, 2, and 3 years were 95.1% (78/82), 92.3% (76/82), and 92.3% (76/82), respectively; and the OS at 1, 2, and 3 years were 68.3% (56/82), 48.8% (40/82) and 31.7% (26/82), respectively. Nine patients suffered from radiation-induced liver disease (RILD), and there were no deaths due to RILD. Cox regression analysis showed that alpha-fetoprotein (AFP) was an independent risk factor for OS (HR=2.304, 95%CI 1.118-4.747;P<0.05). Conclusion: Cyberknife treatment for patients with primary large hepatocellular cancer over 70 years old has higher LC and OS, better curative effect, and less treatment-related adverse reactions.

[Comparison of high-risk human papillomavirus infection rate and genotype distribution between Han and Mongolian women].

Objective: To understand the infection rate and genotype distribution of high risk-human papillomavirus (HR-HPV) and the detection rate of different grades of cervical lesions in Han and Mongolian women in China and provide evidence for the development of screening and vaccination strategies for the prevention and control of cervical cancer in different ethnic groups. Methods: In June 2017, a multicenter, population-based study for cervical cancer screening in low-resource settings in China was conducted in three rural areas: Xiangyuan and Yangcheng counties in Shanxi province, and Etuoke county in Inner Mongolia Autonomous Region. A total of 9 517 women aged 30-65 years were included in the study, and two cervical and vaginal secretion samples were collected from them for HPV and PCR-based HPV DNA tests. The positive samples in any of two tests were used for PCR-based HPV genotyping test by using Sansure-pioneered One-Step Fast Release technology. Women with positive results in any the HPV tests were referred for colposcopy and punch biopsy was given if cervical intraepithelial neoplasia lesion (low-grade lesion or worse) was suspected in colposcopy evaluation. Endocervical curettage was performed if women had an unsatisfactory colposcopy exam (the squamocolumnar junction was not completely visible). Pathological detection result was used as the golden standard of diagnosis. Results: HR-HPV infection rates in Han and Mongolian women were 21.83% (1 842/8 438) and 24.93% (269/1 079), respectively. There were statistical differences in HPV infection rates between the two ethnic groups (χ(2)=5.328, P=0.021). The detection rate of cervical intraepithelial neoplasia grade 1 in Mongolian women (2.83%) was higher than that in Han women (0.87%), and the difference was statistically significant (χ(2)=33.509, P<0.001). There were no significant differences in cervical intraepithelial neoplasia grade 2 or worse detection rate between the two ethnic groups [Mongolian woman: 1.04% (11/1 059), Han Woman: 0.95% (80/8 378), χ(2)=0.069, P=0.793]. Among Han and Mongolian women with cervical intraepithelial neoplasia grade 2 or worse, the three most common HR-HPV types were HPV16, HPV52 and HPV58. There was no significant difference for multiple infection rate between Han and Mongolian women (41.37% vs. 44.35%, χ(2)=0.764, P=0.382). Conclusions: The results show that HPV infection rate in Mongolian women was higher than that in Han women. Close attention should be paid to HPV16, 52 and 58 in the prevention and control of cervical cancer in Han and Mongolian women.