人乳头瘤病毒预防性疫苗的研究进展及应用前景

过去50多年,在子宫颈癌的防治研究进程中,有两大历史性的发现使得人们在人类历史上率先实现了采用一级预防与二级预防相结合的方式有效地控制甚至消除癌症成为可能.第1个历史性的发现是:被誉为"现代细胞学之父"的希腊医生Papanicolaou在1941年,首次阐述了阴道(宫颈)细胞学涂片对诊断子宫颈癌的价值,之后巴氏涂片作为一种子宫颈癌的筛查方法被引入临床,并成为临床医学中最有效的筛查方法[1].     

城市和农村妇女高危型人乳头瘤病毒感染的危险因素分析

目的:探讨影响我国城市和农村地区高危型人乳头瘤病毒(HR-HPV)感染的危险因素,为HR-HPV感染和子宫颈癌的防治工作提供依据。方法:采用横断面调查方法对城市地区(北京和上海)1 569人、农村地区(山西和河南)1 763人进行流行病学调查和妇科检查及高危型人乳头瘤病毒检测(HC-Ⅱ)。利用χ2检验和非条件Logistic回归模型分析HR-HPV感染的危险因素。结果:多因素分析结果显示,影响城市地区HR-HPV感染的危险因素为丈夫婚外性行为、生殖器感染史(STD)、流产次数和吸烟,而细胞学检查史是保护因素。影响农村地区HR-HPV感染的危险因素为初次性交年龄、近5年性伴侣数、丈夫婚外性行为、性生活年限和饮酒。结论:影响城市与农村地区妇女感染HR-HPV的危险因素存在着较大差异。提示,在制定预防和控制宫颈癌以及HR-HPV感染的措施时要因地制宜。     

高危型人乳头瘤病毒载量与子宫颈病变的关系

Objective To determine the association between viral load of high risk human papillomavirus (HR-HPV) and cervical intraepithelial neoplasia (CIN). Methods Cervical exfoliated cells were collected from 18 186 women aged 17 -59 from six urban areas and eight rural areas when they were screened in the cross-sectional population-based studies from 1999 to 2008. HR-HPV was detected by the Hybrid Capture 2 (hc2) system, and viral load was measured by the ratio of relative light units to standard positive control (RLU/PC). RLU/PC was categorized for analysis into four groups: negative [0, 1.00),low viral load [1.0, 10.00), moderate viral load [10.00, 100.00), and high viral load 100. 00. Cervical lesions were diagnosed by biopsies as normal, CIN 1, CIN 2, CIN 3 and squamous cervical cancer (SCC). Association between HR-HPV viral load and CIN was evaluated by unconditional multinomial logistic regression. Results The HR-HPV infection rate of the population was 14. 51% (2515/17 334). 100. 00% (29/29) of SCC,97. 63% (206/211) of CIN 3,93.43% (199/213) of CIN 2,75.04% (421/ 561) of CIN 1 and 10. 17% (1660/16 320) of normal women were positive for HR-HPV DNA. The median RLUs for the HR-HPV positive women with SCC,CIN 3,CIN 2,CIN I and normal were 320. 85,158. 05, 143. 70,125.34 and 9. 64, respectively. There were significant differences among the distributions of viral loads in each lesion (X2=6190. 40,P<0. 01). The severity of CIN increased with the viral load (X2=5493. 35 ,P<0. 01). Compared with the risks of CINs in HR-HPV negative population,the risks of CINs in low,moderate and high viral loads were increased gradually [OR(95% CI) : CIN 1 : 9. 01 (6. 31 -12. 87), 24.96(18.23 -34. 17) and 68.42(51.40 -91.08); CIN 2:26.44(12.07 -57.95),98. 53 (49. 54 -195.98) and 322. 88(168.62 -618. 27) ; CIN 3 + : 72. 89(24.02 -221.18) ; 343. 58(121.81 -969.09) Was 3115.05,2413.95 and 3098.57, respectively. P<0.01) . In each age group of the HR-HPV positive population,the risks of CIN 2 + in the women with moderate or high viral load were higher than the one with low viral load [OR(95%CI):<35: 4. 71(1.23-18.09) and 15.06(4.40-51.49); 35-: 4.01 (1.62-9.90) and 14.09(6. 15 -32.28); 40-: 3.06(1.52 -6. 16) and 7.78(4.05 -14.95); ≥45: 3. 50(1.36 -9. 01) and 7. 57 (3. 13 -18. 30)], and there was a positive correlation between the risk of CIN 2 + and the viral load (Xtrend2was 51. 33,66. 28,53. 64 and 51.00,respectively. P<0. 01). The risk of CIN 2 + was highest among the women aged 40 -with high viral load [0R(95% CI):2.02 (1.15 -3. 52)]. Conclusion There is strong correlation between the HR-HPV viral load and the severity of CIN, and so is the correlation between the HR-HPV viral load and the risk of CIN 2 +. A moderate to high viral load of HR-HPV should be the major risk factor for the cervical cancer and CIN 2 and CIN 3,and there is a higher risk in the women aged 35 or older than the younger ones. Considering both the age and viral load could help the doctors to manage the screening women more effectively.     

高危型人乳头瘤病毒载量与子宫颈病变的关系

Objective To determine the association between viral load of high risk human papillomavirus (HR-HPV) and cervical intraepithelial neoplasia (CIN). Methods Cervical exfoliated cells were collected from 18 186 women aged 17 -59 from six urban areas and eight rural areas when they were screened in the cross-sectional population-based studies from 1999 to 2008. HR-HPV was detected by the Hybrid Capture 2 (hc2) system, and viral load was measured by the ratio of relative light units to standard positive control (RLU/PC). RLU/PC was categorized for analysis into four groups: negative [0, 1.00),low viral load [1.0, 10.00), moderate viral load [10.00, 100.00), and high viral load 100. 00. Cervical lesions were diagnosed by biopsies as normal, CIN 1, CIN 2, CIN 3 and squamous cervical cancer (SCC). Association between HR-HPV viral load and CIN was evaluated by unconditional multinomial logistic regression. Results The HR-HPV infection rate of the population was 14. 51% (2515/17 334). 100. 00% (29/29) of SCC,97. 63% (206/211) of CIN 3,93.43% (199/213) of CIN 2,75.04% (421/ 561) of CIN 1 and 10. 17% (1660/16 320) of normal women were positive for HR-HPV DNA. The median RLUs for the HR-HPV positive women with SCC,CIN 3,CIN 2,CIN I and normal were 320. 85,158. 05, 143. 70,125.34 and 9. 64, respectively. There were significant differences among the distributions of viral loads in each lesion (X2=6190. 40,P<0. 01). The severity of CIN increased with the viral load (X2=5493. 35 ,P<0. 01). Compared with the risks of CINs in HR-HPV negative population,the risks of CINs in low,moderate and high viral loads were increased gradually [OR(95% CI) : CIN 1 : 9. 01 (6. 31 -12. 87), 24.96(18.23 -34. 17) and 68.42(51.40 -91.08); CIN 2:26.44(12.07 -57.95),98. 53 (49. 54 -195.98) and 322. 88(168.62 -618. 27) ; CIN 3 + : 72. 89(24.02 -221.18) ; 343. 58(121.81 -969.09) Was 3115.05,2413.95 and 3098.57, respectively. P<0.01) . In each age group of the HR-HPV positive population,the risks of CIN 2 + in the women with moderate or high viral load were higher than the one with low viral load [OR(95%CI):<35: 4. 71(1.23-18.09) and 15.06(4.40-51.49); 35-: 4.01 (1.62-9.90) and 14.09(6. 15 -32.28); 40-: 3.06(1.52 -6. 16) and 7.78(4.05 -14.95); ≥45: 3. 50(1.36 -9. 01) and 7. 57 (3. 13 -18. 30)], and there was a positive correlation between the risk of CIN 2 + and the viral load (Xtrend2was 51. 33,66. 28,53. 64 and 51.00,respectively. P<0. 01). The risk of CIN 2 + was highest among the women aged 40 -with high viral load [0R(95% CI):2.02 (1.15 -3. 52)]. Conclusion There is strong correlation between the HR-HPV viral load and the severity of CIN, and so is the correlation between the HR-HPV viral load and the risk of CIN 2 +. A moderate to high viral load of HR-HPV should be the major risk factor for the cervical cancer and CIN 2 and CIN 3,and there is a higher risk in the women aged 35 or older than the younger ones. Considering both the age and viral load could help the doctors to manage the screening women more effectively.     

中国宫颈癌防治研究20年历程与成就

宫颈癌是全球女性第四大常见恶性肿瘤,我国发病人数占全球的18.6%,防控形势严峻。经过20年的探索与努力,我国形成了宫颈癌流行病学及病因学科学证据,HPV预防性疫苗取得突破进展,筛查技术日渐成熟以及初步提出适用于不同经济水平条件地区的多种宫颈癌筛查方案。尽管如此,基层卫生服务能力亟待提高,以缩小其与实际需求之间的差距,加速实现全球消除宫颈癌的宏伟目标。     

农村妇女宫颈癌和乳腺癌筛查的实践与探讨

目的通过对农村妇女宫颈癌和乳腺癌的筛查实践,探讨宫颈癌和乳腺癌联合筛查的模式及效果。方法 2009年—2011年襄垣县妇幼保健院对该县适龄农村妇女开展宫颈癌和乳腺癌筛查。结果此次筛查共完成27 517名妇女的宫颈癌筛查,6 122名妇女的乳腺癌筛查,其中宫颈上皮内瘤变Ⅱ级(CINⅡ)及以上病变的患病率为0.49%,早诊率为91.2%。乳腺良性肿瘤33例(0.53%);乳腺癌2例(0.03%),早诊率为50。%结论宫颈癌检查有筛查基础,筛查及早诊、早治效果明显。乳腺癌筛查仍需规范,须加强技术培训,提高筛查水平。筛查体系和技术队伍建设是基层妇女保健服务的保证,对农村妇女同时进行宫颈癌、乳腺癌联合筛查优于单一项目筛查。     

高危型人乳头瘤病毒载量与子宫颈病变的关系

Objective To determine the association between viral load of high risk human papillomavirus (HR-HPV) and cervical intraepithelial neoplasia (CIN). Methods Cervical exfoliated cells were collected from 18 186 women aged 17 -59 from six urban areas and eight rural areas when they were screened in the cross-sectional population-based studies from 1999 to 2008. HR-HPV was detected by the Hybrid Capture 2 (hc2) system, and viral load was measured by the ratio of relative light units to standard positive control (RLU/PC). RLU/PC was categorized for analysis into four groups: negative [0, 1.00),low viral load [1.0, 10.00), moderate viral load [10.00, 100.00), and high viral load 100. 00. Cervical lesions were diagnosed by biopsies as normal, CIN 1, CIN 2, CIN 3 and squamous cervical cancer (SCC). Association between HR-HPV viral load and CIN was evaluated by unconditional multinomial logistic regression. Results The HR-HPV infection rate of the population was 14. 51% (2515/17 334). 100. 00% (29/29) of SCC,97. 63% (206/211) of CIN 3,93.43% (199/213) of CIN 2,75.04% (421/ 561) of CIN 1 and 10. 17% (1660/16 320) of normal women were positive for HR-HPV DNA. The median RLUs for the HR-HPV positive women with SCC,CIN 3,CIN 2,CIN I and normal were 320. 85,158. 05, 143. 70,125.34 and 9. 64, respectively. There were significant differences among the distributions of viral loads in each lesion (X2=6190. 40,P<0. 01). The severity of CIN increased with the viral load (X2=5493. 35 ,P<0. 01). Compared with the risks of CINs in HR-HPV negative population,the risks of CINs in low,moderate and high viral loads were increased gradually [OR(95% CI) : CIN 1 : 9. 01 (6. 31 -12. 87), 24.96(18.23 -34. 17) and 68.42(51.40 -91.08); CIN 2:26.44(12.07 -57.95),98. 53 (49. 54 -195.98) and 322. 88(168.62 -618. 27) ; CIN 3 + : 72. 89(24.02 -221.18) ; 343. 58(121.81 -969.09) Was 3115.05,2413.95 and 3098.57, respectively. P<0.01) . In each age group of the HR-HPV positive population,the risks of CIN 2 + in the women with moderate or high viral load were higher than the one with low viral load [OR(95%CI):<35: 4. 71(1.23-18.09) and 15.06(4.40-51.49); 35-: 4.01 (1.62-9.90) and 14.09(6. 15 -32.28); 40-: 3.06(1.52 -6. 16) and 7.78(4.05 -14.95); ≥45: 3. 50(1.36 -9. 01) and 7. 57 (3. 13 -18. 30)], and there was a positive correlation between the risk of CIN 2 + and the viral load (Xtrend2was 51. 33,66. 28,53. 64 and 51.00,respectively. P<0. 01). The risk of CIN 2 + was highest among the women aged 40 -with high viral load [0R(95% CI):2.02 (1.15 -3. 52)]. Conclusion There is strong correlation between the HR-HPV viral load and the severity of CIN, and so is the correlation between the HR-HPV viral load and the risk of CIN 2 +. A moderate to high viral load of HR-HPV should be the major risk factor for the cervical cancer and CIN 2 and CIN 3,and there is a higher risk in the women aged 35 or older than the younger ones. Considering both the age and viral load could help the doctors to manage the screening women more effectively.     

宫颈癌即时筛查技术效果评价

目的:分析即时检测（POCT）技术筛查宫颈癌及癌前病变的准确性。方法:2020年9月,在山西省襄垣县建立的“自我采样”队列和“医生采样”队列中,采用简单随机抽样的方法从两队列人群中抽取研究对象,分别纳入197和273名。由研究对象自己或妇科医生分别采集宫颈脱落细胞标本并进行检测,采用POCT检测人乳头状瘤病毒（HPV）...     

2006-2017年中国女性乳腺癌和生殖系统癌症发病趋势分析

目的 评估2006-2017年不同年龄和地区女性乳腺癌和生殖系统癌症的发病趋势。方法 结合发病率、人口数计算全国分地区、分年龄的女性乳腺癌、外阴癌、阴道癌、宫颈癌、子宫体癌及卵巢癌的发病数及平均诊断年龄。通过世界标准人口进行标化。采用Joinpoint 4.5.0.1软件计算平均年变化百分比（AAPC）。结果 2006-2017年,6种癌症的合计年龄标化发病率（ASIR）从39.48/10万上升至51.11/10万（AAPC=2.24%,95%CI：1.59%~2.89%）。这一上升趋势在农村地区更加显著（AAPC=4.65%,95%CI：3.67%~5.64%）,而城市地区未见明显上升（AAPC=0.15%,95%CI：-0.26%~0.56%）。除子宫体癌外,其他5种癌症发病均呈上升趋势。宫颈癌的ASIR在城市和农村地区上升趋势相近。乳腺癌、阴道癌和外阴癌的ASIR在城市地区无明显上升趋势,而在农村地区明显上升。卵巢癌的ASIR在城市地区呈下降趋势,而在农村地区则呈上升趋势。从发病年龄上看,除子宫体癌外,所有女性癌症平均诊断年龄均呈上升趋势。通过世界标准人口标化后,仅在宫颈癌和阴道癌中观察到标化平均诊断年龄的上升,从49.11岁和55.15岁分别上升至52.13岁和58.81岁。结论 2006-2017年,女性癌症标化发病率总体呈上升趋势,且农村地区上升趋势高于城市地区。同时,农村居民的医疗资源可及性需进一步提升,保证医疗保健服务和早诊早治,从而弥合女性癌症城乡差距。     

中国大陆女性体检人群中人乳头瘤病毒型别感染率及九价疫苗中HPV各型别分布的系统评价

目的：探讨人乳头瘤病毒(human papillomavirus, HPV)在我国大陆女性体检人群中感染及型别分布特征,为体检人群接种九价HPV疫苗提供科学依据。方法：采用系统评价法综合评价检索1995年1月1日～2016年12月31日在Pubmed、Medline、知网、维普和万方数据库收录的所有关于中国正常女性人群中发表的有关HPV感染及型别分布的相关研究。由 2 位研究者独立筛选文献、提取数据资料和评价纳入研究的文献质量,采用Stata 12.0 软件进行分析。结果：研究共纳入19篇文献,总人数为504 566人;随机效应模型结果显示,我国正常体检女性人群中HPV的感染率为16.18%[95%CI(14.16,18.20)%],高危型、低危型的感染率分别为12.95%和3.28%,九价疫苗中高危型和低危型的感染率为10.59%和1.56%,而九价疫苗中所有型的感染率是12.15%[95%CI(10.18,14.13)%],其中大陆体检女性人群中比较常见的型别是HPV16/52/58/33/18/68。七大区的HPV感染率及型别均不同,正常体检人群女性中总HPV、高危型以及低危型的感染率最高的是华东地区,分别为17.54%[95%CI(16.82,18.27)%]、14.17%[95%CI(13.50,14.83)%]、3.75%[95%CI(2.11,6.11)%],总HPV感染率最低的是西北8.79%[95%CI(7.47,10.26)%],高危型感染率最低的是西南地区3.04%[95%CI(6.80,8.70)%],低危型感染率最低的是西南地区0.14%[95%CI(0.02,0.49) %];九价HPV疫苗中高危型的感染率最高的华中和华东地区分别为11.36%[95%CI(9.33,13.40)%]和11.36%[95%CI(10.75,11.97)%],最低的是东北地区为7.83%[95%CI(7.18,8.51)%];九价HPV疫苗中低危型的感染率最高的华北地区为3.50%[95%CI(1.93,5.80)%],感染率最低的是华中地区为0.30% [95%CI(0.06,0.87)%];九价HPV疫苗中所有型的感染率最高的华北地区为12.75%[95%CI(9.64,16.42)%],最低是东北地区为8.34%[95%CI(7.67,9.03)%]。正常体检女性人群中HPV总的感染率、高危型和低危型感染率均是南方高于北方,差异有统计学意义;九价疫苗的低危型感染率则相反,南北方感染的HPV型别以及感染率均不同,而九价疫苗中高危型及全部型别的南北方感染率差异无统计学意义。经非条件Logistic 回归分析,使用GP5+/6+引物系统检测出的HPV调整感染率显著高于其它引物系统(P<0.001);总HPV调整感染率随发表年限增加而增加(P<0.001)。结论：中国大陆地区健康体检的女性人群中HPV的感染率较高,常见的型别为HPV16/52/58/33/18,不同地区型别分布及感染率不同其中华中地区最高,西北地区最低,且南北方存在差异。而在体检人群中接种九价HPV疫苗其防治效果明显,但是还需要进行宫颈癌的筛查。 受纳入研究的文献检测方法多样性和质量的限制,上述结论尚需要更多研究予以证实。