Human papillomavirus genotype contribution to cervical cancer and precancer: Implications for screening and vaccination in Japan

To obtain baseline data for cervical cancer prevention in Japan, we analyzed human papillomavirus (HPV) data from 5045 Japanese women aged less than 40 years and diagnosed with cervical abnormalities at 21 hospitals during 2012‐2017. These included cervical intraepithelial neoplasia grade 1 (CIN1, n = 573), CIN2‐3 (n = 3219), adenocarcinoma in situ (AIS, n = 123), and invasive cervical cancer (ICC, n = 1130). The Roche Linear Array was used for HPV genotyping. The HPV type‐specific relative contributions (RCs) were estimated by adding multiple infections to single types in accordance with proportional weighting attributions. Based on the comparison of type‐specific RCs between CIN1 and CIN2‐3/AIS/ICC (CIN2+), RC ratios were calculated to estimate type‐specific risks for progression to CIN2+. Human papillomavirus DNA was detected in 85.5% of CIN1, 95.7% of CIN2‐3/AIS, and 91.2% of ICC. Multiple infections decreased with disease severity: 42.9% in CIN1, 40.4% in CIN2‐3/AIS, and 23.7% in ICC (P < .0001). The relative risk for progression to CIN2+ was highest for HPV16 (RC ratio 3.78, 95% confidence interval [CI] 3.01‐4.98), followed by HPV31 (2.51, 1.54‐5.24), HPV18 (2.43, 1.59‐4.32), HPV35 (1.56, 0.43‐8.36), HPV33 (1.01, 0.49‐3.31), HPV52 (0.99, 0.76‐1.33), and HPV58 (0.97, 0.75‐1.32). The relative risk of disease progression was 1.87 (95% CI, 1.71‐2.05) for HPV16/18/31/33/35/45/52/58, but only 0.17 (95% CI, 0.14‐0.22) for HPV39/51/56/59/66/68. Human papillomavirus 16/18/31/33/45/52/58/6/11 included in a 9‐valent vaccine contributed to 89.7% (95% CI, 88.7‐90.7) of CIN2‐3/AIS and 93.8% (95% CI, 92.4‐95.3) of ICC. In conclusion, our data support the Japanese guidelines that recommend discriminating HPV16/18/31/33/35/45/52/58 genotypes for CIN management. The 9‐valent vaccine is estimated to provide over 90% protection against ICC in young Japanese women.     

Knowledge,Attitudes, and Practices Regarding Cervical Cancer Screening among HIV-infected Women at Srinagarind Hospital: A Cross-Sectional Study

Introduction: In recent years, the lives of HIV-infected patients in Thailand have improved significantly due to continuous advances in treatment. However, the rate of cancer related to HIV infection (especially cervical cancer) is likely to increase. Although the World Health Organization (WHO) recommends Papanicolaou testing in all HIV-infected women, few of these patients receive this kind of screening in Thailand. Therefore, we conducted this study to evaluate the knowledge, attitudes, and practices of these patients with regard to cervical cancer screening. Materials and Methods: This cross-sectional study was conducted in HIV-infected women aged 18-65 years from April to November 2019 via a self-administered cervical cancer screening questionnaire, which consisted of four parts: demographic data, knowledge, attitudes, and practices. Results: Three hundred HIV-infected women were recruited. Most of the participants had good attitudes toward screening and practiced adequate screening (75.3% and 71.3%, respectively). However, only 62 participants (20.7%) demonstrated adequate knowledge. The crucial factors that were associated with adequate screening practice were age 40-49 years-old (AOR =3.26, 95%CI=1.02-10.37), CD4 cell count (AOR = 3.41, 95%CI = 1.29-8.99), having been advised about cervical cancer screening (AOR= 6.23, 95%CI 1.84-21.07), and attitude toward screening (AOR= 5.7, 95%CI = 2.23-14.55). The major reasons for not undergoing screening were embarrassment (41.86%), lack of symptoms (41.86%), fear of the results (36.04%), and fear of pain (36.04%). Conclusion: The reasons for inadequate testing were disregard and misconceptions about the procedure. To prevent invasive cervical lesions in HIV-infected women, health care providers should inform these patients about the importance of regular cervical cancer screening.     

CyclinA1 Promoter Methylation in Self-Sampling Test

Background: Self sampled HPV testing is a cervical cancer screening method . However, cytology in self-sampled specimen cannot be used as a triage test.  Therefore, other methods for triage should be considered. CyclinA1 (CCNA1) promoter methylation has strong association with cervical precancerous and cancerous lesion. The objective of this study was to compare the diagnostic value of CCNA1 and self-sampled specimen for detecting high-grade cervical intraepithelial lesions or worse (CIN2+). Materials and Methods: A cross sectional study was conducted. Women with abnormal cytology or positive for high risk HPV (hrHPV) indicated for colposcopic examination were enrolled.  Self-collected sampling for hrHPV DNA (SS-HPV) and CCNA1 were performed. hrHPV DNA testing was done by Cobas 4800 method. CCNA1 promoter methylation was detected by CCNA1 duplex methylation specific PCR. Histopathologic result as CIN2+ obtaining from colposcopic directed biopsy or excisional procedure  was considered as positive a gold standard. The results of hrHPV and CCNA1 were reported as positive or negative. Sensitivity specificity, positive predictive value, and negative predictive value of SS-HPV and CCNA1 were calculated by comparing the results with the gold standard. Results: Two hundreds and eighty women were recruited. High-grade cervical lesions and cervical cancer (CIN2+) were diagnosed in 21.8% (61 cases) of the patients. The most common type of hrHPV was non 16, 18 subtype, followed by HPV16 and 18. CCNA1 was positive in 13 patients out of whom, twelve were CIN2+. Sensitivity of CCNA1 was 19.7 % and its  specificity and accuracy were 99.5% and 82.14%, respectively.  The sensitivity of SS-HPV was 70.5%, and its  specificity and accuracy were 39.2% and 43.3%, respectively. Conclusion:  Due to high specificity and positive predictive value of CCNA1, it can be used as alarming sign of having high-grade cervical intraepithelial lesions, especially in patient who has positive hrHPV DNA test based on self-collected sampling.     

Health Literacy,Knowledge on Cervical Cancer and Pap Smear and Its Influence on Pre-Marital Malay Muslim Women Attitude towards Pap Smear

Background: Cervical cancer is preventable. In Malaysia, women are found to have good awareness of the disease and yet, the Pap smear uptake is still poor. Measuring health literacy level could explain this discrepancy. This study aims to determine the relationship between health literacy, level of knowledge of cervical cancer and Pap smear with attitude towards Pap smear among women attending pre-marital course. Methods: A cross sectional study was performed in three randomly selected centres that organised pre-marital courses. All Malay Muslim women participants aged 18 to 40 years old were recruited while non-Malaysian, illiterate, and had hysterectomy were excluded. Validated self-administered questionnaires used were European Health Literacy Questionnaire (HLS-EU-Q16 Malay) and Knowledge and attitude towards Cervical Cancer and Pap Smear Questionnaire. The mean percentage score (mean± SD) was calculated, with higher scores showed better outcomes. Multiple linear regression was used to measure the relationship of independent variables with attitude towards Pap smear. Results: A total of 417 participants were recruited with a mean age of 24.9 ± 3.56 years old. Prevalence of awareness of cervical cancer was 91.6% (n=382, 95% CI: 89.0%, 94.2%) and mean percentage score was 74.7%±7.6. Prevalence of awareness of Pap smear was 59.0% (n=246, 95% CI: 54.2%, 63.8%) and mean percentage score was 80.2% ± 6.5. The health literacy mean score was 13.3±3.6, with minimum score 0 and maximum score 16. The mean percentage score of attitudes towards Pap smear was 64.8%±9.3. Multiple linear regression analysis demonstrated significant relationship between health literacy (p=0.047) and knowledge of Pap smear (p<0.001) with attitude towards Pap smear. Conclusion: A higher health literacy with high knowledge of Pap smear improves the attitude towards Pap smear. Pre-marital course is an opportunistic platform to disseminate information to improve health literacy and knowledge of cervical cancer and Pap smear screening.     

后装腔内插植放疗与三维后装腔内放疗治疗局部晚期宫颈癌的疗效与剂量学比较

目的探讨后装腔内插植放疗与三维后装腔内放疗治疗局部晚期宫颈癌的疗效与剂量学差异。方法将212例局部晚期宫颈癌患者,按照治疗方法的不同分为A组(106例)和B组(106例)。在体外三维适形调强放疗的基础上,A组采用后装腔内插植放疗,B组采用三维后装腔内放疗。对比两组近期疗效、并发症发生率以及剂量学差异。结果B组患者高危临床靶区D100、D90和中危临床靶区D100、D90均明显低于A组,膀胱、直肠、乙状结肠的D2cm3均明显高于A组,差异均有统计学意义(P﹤0.01)。A组患者总有效率明显高于B组,放射性直肠炎、放射性膀胱炎发生率均明显低于B组,差异均有统计学意义(P﹤0.01)。结论后装腔内插植放疗能够在提升肿瘤组织受照剂量的同时,降低危及器官的受照剂量,提升近期缓解率、控制率,减少不良反应。     

贝伐珠单抗联合长春瑞滨二线治疗复发转移性宫颈癌患者的近期疗效

目的:观察贝伐珠单抗联合长春瑞滨治疗复发转移性宫颈癌的近期疗效及不良反应。方法:回顾性分析2014年1月至2016年12月贵州省人民医院收治的34例复发转移性宫颈癌患者的临床资料,所有患者均使用贝伐珠单抗联合长春瑞滨,21天为1个周期,行4～6个周期治疗,评价疗效及评定不良反应级别。结果:34例宫颈癌患者中无完全缓解患者,部分缓解7例（20.6%）、疾病稳定20例（58.8%）、疾病进展7例(20.6%）,总有效率为 20.6%（7/34）,疾病控制率为79.4%（27/34）。34例患者常见不良反应程度均较轻,可以耐受。结论:贝伐珠单抗联合长春瑞滨方案治疗复发转移性宫颈癌患者近期疗效好,其不良反应患者可耐受,远期疗效有待进一步的研究。     

多b值DWI-MRI在宫颈癌放化疗效果评价中应用价值

目的:探讨磁共振多b值弥散加权成像对宫颈癌放化疗效果的应用价值。方法:选取51例经临床证实为IIa期以上宫颈癌患者,并接受放化疗的治疗,在治疗前、治疗后2~3周及治疗结束后行常规MRI及多b值DWI检查,测量治疗前、后肿瘤ADC值及最大径,分析放化疗前后ADC值差异性以及与肿瘤最大径退缩率的相关性。结果:宫颈癌于放化疗后ADC值升高,放化疗前、放化疗后2~3周及结束时ADC值分别是（0.81±0.13）×10-3 mm2/s、（1.18±0.14）×10-3 mm2/s、（1.47±0.22）×10-3 mm2/s,两两之间差异具有统计学意义(P＜0.01);放化疗前与放化疗2~3周的ADC值差值(T值)为（0.37 ±0.13)×10-3 mm2/s,放化疗前后肿瘤最大径退缩率为0.78±0.12,放化疗前、放化疗后2~3周及结束时ADC值与肿瘤最大径退缩率均无相关性,T值与肿瘤最大径退缩率有正相关性(P＜0.05)。结论:宫颈癌病灶ADC值放化疗后升高,放化疗后ADC值早期升高幅度与肿瘤最大径退缩率具有正相关性,可作为预测宫颈癌化疗治疗效果的理想手段之一。     

2015年重庆市肿瘤登记地区宫颈癌疾病负担分析

目的:了解2015年重庆市宫颈癌发病率、死亡率、伤残调整寿命年。方法:收集整理2015年重庆市11个肿瘤登记点报告的宫颈癌发病死亡病例（ICD-10编码为C53）。统计分析宫颈癌发病率、死亡率、标化发病率、标化死亡率、发病和死亡截缩率、发病或死亡累积危险度、早死所致的寿命损失年、残疾所致寿命损失年、伤残调整寿命年等指标。城市与农村宫颈癌发病率与死亡率的比较采用χ2检验。 结果:2015年重庆市肿瘤登记地区共报告宫颈癌新发病例916例,宫颈癌粗发病率为18.29/105,标化发病率为14.26/105,标化发病率农村（15.60/105）高于城市（12.32/105）,差异有统计学意义（P<0.001）。2015年共报告宫颈癌死亡病例283例,粗死亡率为5.65/105,标化死亡率为3.98/105。2015年重庆市宫颈癌截缩发病率为32.60/105,截缩死亡率为8.32/105,发病率与死亡率累积危险度分别为1.41%与0.49%。宫颈癌导致的DALYs、YLDs 和YLLs分别是6.76千人年、5.00千人年与1.76千人年。结论:重庆市宫颈癌发病率与死亡率高于全国平均水平,疾病负担重,疾病负担农村高于城市。     

p16、Ki67及FRα预测低度宫颈上皮内瘤变转归的研究进展

宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)已发现与宫颈癌密切相关,根据异常程度分3级CIN(CIN1,CIN2和CIN3)。约60%的CIN1可自然消退,仅有少部分发生进展。目前,迫切需要一些生物标志物作为预测因子来预测病变的转归。经检索国内外文献发现,目前大部分研究结果发现生物标志物p16、Ki67的染色结果对于CIN1的预后有预测意义,并且有部分学者研究了p16/Ki67双染结果也可以很好的预测,而目前仅少数人研究了FRα在预测CIN1转归时的意义,认为FRα可能有一定预测价值。关于这些生物标志物的预测价值,还需要其他大型的、长时间的临床随访来进一步研究它们的准确性和可靠性,也需要进行更加深入的研究去发现其他更为精准的标志物。     

HPV治疗性疫苗的研究进展

宫颈癌是影响全球女性健康的公共卫生问题。持续的高危型HPV感染是宫颈癌的主要致病因素。目前,HPV预防性疫苗已经在全球范围内逐渐广泛开展,但其对已感染HPV的女性没有治疗作用。迄今,多种治疗性疫苗已用于临床前模型和临床试验,包括肽和蛋白质疫苗、活载体疫苗、DNA疫苗等,并已经显示出良好的安全性和耐受性,为宫颈癌的防治工作带来了希望和动力。但其仍存在免疫原性低、需要寻找更多新的靶抗原基因等不足,仍需进一步研究。