Knowledge, Attitude and Practice about Human Papillomavirus and HPV Vaccine in Chinese Mainland: A Meta-analysis
-
摘要:目的
了解和评价中国大陆地区女性对人乳头瘤病毒及HPV疫苗相关知识的认知、态度和行为, 为预防和消除宫颈癌提供理论依据。
方法检索1995年1月1日到2021年1月31日在PubMed、Medline、CNKI和万方数据库等数据库收录的所有关于中国大陆地区女性人群中发表的有关HPV病毒及HPV疫苗相关知识的认知、态度和行为因素的相关研究。由两位研究者独立筛选文献、提取数据资料和评分≥5分的文献。卡方检验评价其异质性; Begg' s检验评价发表偏倚。
结果共有33篇文献纳入研究, 总人数为46013人。
结果显示: 人群HPV总知晓率为65.9%, 其中HPV总知晓率最低的是东北地区、农村地区及中学生分别为16.0%、41.2%和14.4%, 而最高的是华北地区、城镇及大学生人群分别为77.4%、56.3%和71.0%。人群HPV相关知识的主要来源是网络/微信公众号为38.9%, 家人/朋友来源最低为4.5%。人群对HPV疫苗相关知识知晓率为41.4%, 其中HPV疫苗相关知识总知晓率最高的是华东地区和医务人员分别为51.8%和69.7%, 而最低的是西南地区人群和中学生分别为23.6%和12.7%。
结论为尽快实现我国在2030年全面消除宫颈癌目标, 后续应加强人群对HPV和HPV疫苗相关知识的认知。
Abstract:ObjectiveTo understand and evaluate the knowledge, attitude and practice of female human papillomavirus and HPV vaccine in Chinese mainland.
MethodsWe searched the relevant studies about the knowledge, attitude and behavior factors of HPV infection and HPV vaccine published in PubMed, MEDLINE, CNKI and Wanfang databases about Chinese mainland women from January 1, 1995 to January 31, 2021.Two researchers independently screened the literatures, extracted data and the literatures with quality score≥5 points.Chi square test was used to evaluate its heterogeneity.Begg' s test was used to evaluate publication bias.
ResultsA total of 33 literatures were included, with a total number of 46013 people.The results showed that the total awareness rate of HPV in the population was 65.9%, the lowest rates were 16.0%, 41.2% and 14.4% in Northeast, rural areas and middle school students, respectively; while the highest rates of HPV were 77.4%, 56.3% and 71.0% in Central China, cities and towns and college students, respectively.The main source of HPV knowledge was the network/WeChat official account number (38.9%), and the lowest was family/friend (4.5%).The population's awareness rate of HPV vaccine related knowledge was 41.4%, the highest rates were 51.8% and 69.7% in East China and medical staff, respectively, while the lowest were 23.6% and 12.7% in Southwest and middle school students.
ConclusionIn order to achieve the total elimination of cervical cancer in China by 2030 as soon as possible, people should strengthen their awareness of HPV and HPV vaccine related knowledge.
-
Key words:
- HPV infection /
- Ucognition /
- System evaluation
-
0 引言
目前,化学治疗仍是三阴性乳腺癌的主要治疗方法之一,但是肿瘤细胞对化疗药物的耐药性严重影响了治疗效果,化疗药物与肿瘤细胞的接触是诱导继发性耐药的主要原因[1]。由于阿霉素是乳腺癌化学方案的常用药物[2],本研究观察阿霉素对三阴性乳腺癌耐药性的诱导作用并探究其机制。
ATP结合盒(ABC)转运蛋白在耐药的发展中起着至关重要的作用。ATP结合盒亚家族G成员2(ATP-binding cassette, sub-family G member 2, ABCG2)能排出大量异质化合物,导致耐药,引起治疗抵抗[3]。细胞耐药性的产生及耐药蛋白的表达受多种转录因子的调控。有研究报道cMyc能够调控包括ABCG2在内的ABC转运蛋白的表达[4]。cMyc是一个多功能的转录因子,参与调节细胞对阿霉素的敏感度[5],而cMyc的表达受其上游基因Stat3的调控。Stat3在肿瘤组织中异常激活,引发其下游靶基因cMyc转录,从而使正常细胞转化为癌细胞,并增加肿瘤细胞的耐药性[6]。因此,本研究观察阿霉素对MDA-MB-468细胞耐药性的诱导作用并探讨Stat3-cMyc通路是否介导了耐药性的发生。
1 材料与方法
1.1 细胞株、试剂、仪器
人乳腺癌MDA-MB-468细胞株购自美国标准细胞库(American type culture collections, ATCC)。本研究实验剂和仪器包括:RPMI 1640培养基(Hyclone,美国)、青霉素/链霉素(索莱宝,北京,中国)、胎牛血清(四季青,杭州,中国)、阿霉素(索莱宝,北京,中国)、RIPA裂解液/苯甲基磺酰氟(索莱宝,北京,中国)、聚偏二氟乙烯膜(Millipore,Billerica,美国)、ABCG2抗体(Abcam,Cambridge,美国)、WP1066抑制剂(Selleckchem,上海,中国)和二甲基亚砜(索莱宝,北京,中国)等。
1.2 细胞培养
人乳腺癌MDA-MB-468细胞用含10%FBS和1%青霉素/链霉素的RPMI 1640在37℃、5%CO2培养箱中培养。以不同浓度的阿霉素(0、0.05、0.1和0.5 μmol/L)孵育细胞24 h,观察并筛选最适阿霉素浓度进行后续实验。
1.3 MTT法检测
细胞以3 000个/孔的密度接种至96孔板,然后分别加入终浓度为0、0.05、0.1和0.5 μmol/L的阿霉素。24 h后,每孔加入20 μl MTT溶液(5 mg/ml)继续培养4 h,吸弃培养液,每孔加150 μl DMSO溶液,振荡15 min后测定570 nm处的吸光度(OD570)。
1.4 细胞爬片及免疫荧光染色
将盖玻片置于24孔板孔底,分别将MDA-MB-468和MDA-MB-468/ADM细胞以1×104个/孔接种,待细胞爬满盖玻片后进行免疫荧光染色。用PBS轻轻冲洗后在4%多聚甲醛中固定15 min。PBS洗涤爬片3次,山羊血清封闭1 h。将细胞用ABCG2一抗在4℃冰箱中孵育、过夜。PBS洗涤后,用二抗于37℃温育1 h。PBS洗涤细胞,用DAPI染色10 min,再次洗涤3次后滴加荧光防淬灭剂,观察免疫荧光染色并拍照。
1.5 蛋白质印迹分析
抽提各组细胞的总蛋白,利用BCA法测定总蛋白浓度,以每个泳道20 μg浓度的蛋白样品上样,经SDS-PAGE电泳后,利用半干电转化法将蛋白转移至PVDF膜上,经过封闭、一抗(稀释倍数1:1 000)孵育、TBST洗脱、HRP标记的二抗(稀释倍数1:5 000)孵育、TBST再洗脱等步骤后,用增强化学发光法检测信号及X线片曝光,并且经定影显影处理,获得清晰条带。
1.6 统计学方法
运用SPSS13.0统计软件进行分析,所有结果采用(x±s)表示,组间均数的比较采用独立t检验(双侧),P < 0.05为差异有统计学意义。
2 结果
2.1 持续低剂量阿霉素刺激诱导MDA-MB-468细胞产生耐药性
不同浓度阿霉素作用于MDA-MB-468细胞24 h后可见0.05 μmol/L与0.1 μmol/L浓度的阿霉素未引起细胞明显的损伤,大部分细胞生长良好。当浓度增加到0.5 μmol/L时,几乎所有细胞都受损,可见大量坏死细胞;MTT法测得在0.05 μmol/L、0.1 μmol/L及0.5 μmol/L浓度下阿霉素对MDA-MB-468细胞的抑制率分别为0.14、0.20、0.38,而且阿霉素对MDA-MB-468细胞的半数最大效应浓度(concentration for 50% of maximal effect, EC50)为0.94 μmol/L(P=0.038)。综合以上结果,我们选用0.1 μmol/L的阿霉素继续进行后续研究。
用0.1 μmol/L的阿霉素持续刺激MDA-MB-468细胞4周后获得耐药细胞,命名为MDA-MB-468/ADM。MTT实验检测MDA-MB-468/ADM细胞对阿霉素敏感度,结果显示MDA-MB-468/ADM的EC50为5.2 μmol/L,较MDA-MB-468的EC50(0.94 μmol/L)显著升高(P=0.041),说明长期使用0.1 μmol/L的阿霉素后,MDA-MB-468细胞对阿霉素的敏感度显著下降,产生耐药,见图 1。
2.2 MDA-MB-468/ADM细胞中高表达耐药蛋白ABCG2
与正常MDA-MB-468细胞相比,MDA-MB-468/ADM细胞中代表ABCG2表达水平的红色荧光明显增多增强,见图 2A。Western blot检测结果也表明了MDA-MB-468/ADM细胞中ABCG2的高表达,见图 2B。提示用0.1 μmol/L阿霉素持续刺激后,三阴性乳腺癌MDA-MB-468细胞对阿霉素产生耐药。
图 2 MDA-MB-468/ADM细胞中耐药蛋白ABCG2的表达Figure 2 Expression of drug resistance protein ABCG2 in MDA-MB-468/ADM cellsA: Immunofluorescence staining results showed the increased expression of ABCG2 (red) in MDA-MB-468/ADM cells, staining with DAPI (blue); B: Western blot analysis results showed high expression of ABCG2 in MDA-MB-468/ADM cells (n=3, *: P < 0.05)2.3 MDA-MB-468/ADM细胞高表达p-Stat3与cMyc
为探究MDA-MB-468细胞对阿霉素产生耐药的机制,我们进一步检测了MDA-MB-468/ADM细胞中转录因子p-stat3与cMyc的表达水平,观察MDA-MB-468细胞对阿霉素耐药性的产生是否与Stat3-cMyc途径有关。Western blot结果显示,MDA-MB-468/ADM中p-Stat3与cMyc的表达均明显升高,而两组细胞中总的Stat3表达水平未见显著变化。这些结果表明Stat3的激活和cMyc表达的增多可能参与了MDA-MB-468细胞对阿霉素耐药性的产生,见图 3。
2.4 抑制Stat3活化可下调cMyc及ABCG2的表达
为进一步证明Stat3-cMyc途径在阿霉素诱导三阴性乳腺癌MDA-MB-468细胞耐药性产生中的作用,我们用Stat3磷酸化的抑制剂WP1066抑制Stat3活化,观察转录因子cMyc的表达是否受到影响。结果显示WP1066(1.25 μmol/L)作用于MDA-MB-468/ADM细胞后,磷酸化的Stat3显著降低(P=0.014),同时cMyc表达水平明显下降(P=0.044)。另外WP1066处理后MDA-MB-468/ADM细胞耐药蛋白ABCG2的表达也显著减少(P=0.000)。这些结果进一步说明阿霉素通过Stat3-cMyc途径诱导了MDA-MB-468细胞耐药性的产生,而抑制Stat3的活化后,耐药蛋白表达减少,细胞的耐药性减弱,见图 4。
2.5 抑制Stat3活化增强了MDA-MB-468/ADM细胞对阿霉素的敏感度
由于WP1066下调了耐药蛋白ABCG2的表达,因此我们进一步通过MTT法检测MDA-MB-468/ADM细胞对阿霉素敏感度的变化。结果显示,阿霉素对MDA-MB-468/ADM细胞的EC50为6.774 μmol/L,而在使用WP1066之后的EC50降低至1.29 μmol/L(P=0.000),这表明WP1066抑制Stat3的活化增强了MDA-MB-468/ADM细胞对阿霉素的敏感度,见图 5。
3 讨论
目前肿瘤细胞的耐药性是临床治疗的难点与研究的热点,阐明肿瘤耐药的机制可以为肿瘤的治疗提供新的治疗方向和靶点。
本研究应用低剂量阿霉素持续诱导人三阴性乳腺癌MDA-MB-468细胞,导致细胞产生耐药性,对阿霉素的敏感度显著下降,耐药蛋白ABCG2表达增高。为探究MDA-MB-468细胞对阿霉素产生耐药的机制,本实验进一步检测了MDA-MB-468/ADM细胞中转录因子p-stat3与cMyc的表达水平,观察MDA-MB-468细胞对阿霉素耐药性的产生与Stat3-cMyc途径有关。为进一步证明Stat3-cMyc途径在阿霉素诱导三阴性乳腺癌MDA-MB-468细胞耐药性产生中的作用,实验用Stat3磷酸化的抑制剂WP1066抑制Stat3活化,发现转录因子cMyc的表达也受到影响。进一步的机制研究揭示了Stat3-cMyc通路在阿霉素诱导的耐药中具有重要作用。
文献报道,Stat3信号通路与肿瘤细胞对化疗的耐药性有关[7]。Stat3的激活可以帮助癌细胞逃避由药物引起的死亡,从而诱发耐药性。Yue等[8]证明了Stat3的过度活化可以促进顺铂耐药的卵巢癌进展,相反,如果抑制Stat3信号通路则会促进耐药性癌细胞的凋亡,增加癌细胞对各种药物的敏感度。Li等[9]研究也有相似的发现,抑制Stat3信号通路后人胃癌细胞的凋亡增强,耐药性减弱。那么Stat3在三阴性乳腺癌耐药性的产生中有何作用?文献报道,乳腺癌组织中Stat3的活化增强与乳腺癌的临床分期和侵袭转移密切相关[10]。多种致癌性细胞因子与细胞膜的相应受体结合后导致Stat3与酪氨酸磷酸化通道相偶联后被激活,激活后的Stat3可在核内与特异性DNA启动子相结合,调节cMyc、Oct4、Sox2等相关基因表达[11]。作为调节多种转录因子功能的重要枢纽,Stat3有望成为肿瘤基因治疗中的有效靶点。有研究表明,在肿瘤中cMyc的表达水平与耐药性有关[4, 12-13],cMyc能够调控ABC转运蛋白的表达水平,而ABCG2与肿瘤细胞的耐药性直接相关,但Stat3/cMyc在三阴性乳腺癌产生耐药性方面的影响及机制却未见报道。
本研究发现低浓度(0.1 μmol/L)阿霉素持续刺激使MDA-MB-468细胞对阿霉素的敏感度明显降低,MDA-MB-468/ADM细胞中p-Stat3和cMyc的表达较MDA-MB-468细胞显著增加,这些发现与上述文献中对Stat3和cMyc在肿瘤耐药性中的作用相一致。另外,刘丽等[6]在喉鳞癌细胞的研究中也揭示了Stat3-cMyc通路的重要作用,与本研究的结果相吻合。由此推测,MDA-MB-468/ADM对阿霉素耐药的机制很可能与Stat3的激活和p-Stat3介导的cMyc表达的增多有关。为进一步证明Stat3-cMyc通路在阿霉素诱导的乳腺癌耐药性中的关键作用,本实验应用WP1066抑制MDA-MB-468/ADM中Stat3的活化,发现随着p-Stat3的降低,cMyc和ABCG2的表达也相应下降,这与Granato等[14]证实抑制Stat3信号可下调cMyc的表达一致。再次MTT检测发现WP1066作用后MDA-MB-468/ADM细胞对阿霉素的敏感度显著增强,这与Li等[9]研究结果一致。
总之,本实验结果表明阿霉素可以诱导Stat3活化,上调转录因子cMyc及耐药蛋白ABCG2的表达,促进了三阴性乳腺癌MDA-MB-468细胞对阿霉素耐药性的产生。因此,抑制Stat3的表达与活化可有效逆转乳腺癌对阿霉素的耐药性,特异性靶向Stat3-cMyc途径联合化疗药物治疗有望成为一种有效治疗乳腺癌的新措施,改善乳腺癌患者的预后。
Competing interests: The authors declare that they have no competing interests.作者贡献:石郑阳:数据分析、文章撰写郝金奇:数据分析石继海:课题指导苏征、刘书君:文献检索张希、徐慧芳:核对数据高静茹、付颖:提取数据、资料整理乔友林、余艳琴:课题设计、数据核对、指导文章 -
表 1 人群HPV相关知识知晓情况
Table 1 Awareness of HPV related knowledge in population
表 2 HPV知晓情况的亚组分析
Table 2 Subgroup analysis of HPV awareness
表 3 人群HPV疫苗相关知识知晓情况
Table 3 Awareness of HPV vaccine related knowledge in population
表 4 HPV疫苗相关知识的知晓情况
Table 4 Awareness of HPV vaccine related knowledge
表 5 人群对HPV及HPV疫苗相关知识的来源
Table 5 Sources of people's knowledge about HPV and HPV vaccine
表 6 相关研究的发表偏倚
Table 6 Publication bias of related studies
-
[1] Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3): 209-249. doi: 10.3322/caac.21660
[2] Lu Y, Li P, Luo G, et al. Cancer attributable to human papillomavirus infection in China: Burden and trends[J]. Cancer, 2020, 126(16): 3719-3732. doi: 10.1002/cncr.32986
[3] Brisson M, Kim JJ, Canfell K, et al. Impact of HPV vaccination and cervical screening on cervical elimination: a comparative modelling analysis in 78 low-income and lower-middle-income countries[J]. Lancet, 2020, 395(10224): 575-590. doi: 10.1016/S0140-6736(20)30068-4
[4] Arbyn M, Weiderpass E, Bruni L, et al. Estimates of incidence and mortality of cervical cancer in 2018: a worldwide analysis[J]. Lancet Glob Health, 2020, 8(2): e191-e203. doi: 10.1016/S2214-109X(19)30482-6
[5] Rasheed Z. Why is cancer becoming a global endemic today?[J]. Int J Health Sci (Qassim), 2020, 14(5): 1-2.
[6] Cain JM. Answering the Call to Accelerate the Elimination of Cervical Cancer[J]. Rev Bras Ginecol Obstet, 2019, 41(2): 67. doi: 10.1055/s-0039-1679864
[7] Ning Y, Liu Y, Xu XY, et al. Knowledge of Cervical Cancer, Human Papilloma Virus (HPV) and HPV Vaccination Among Women in Northeast China[J]. J Cancer Educ, 2020, 35(6): 1197-1205. doi: 10.1007/s13187-019-01582-7
[8] Lin W, Wang Y, Liu Z, et al. Inequalities in Awareness and Attitude towards HPV and Its Vaccine between Local and Migrant Residents Who Participated in Cervical Cancer Screening in Shenzhen, China[J]. Cancer Res Treat, 2020, 52(1): 207-217. doi: 10.4143/crt.2019.053
[9] Lin W, Zhou L, Hu H, et al. The number and gender of children synergistically impact on a mother's practice of human papillomavirus testing and attitudes towards vaccination in Shenzhen, China[J]. Cancer Epidemiol, 2020, 65: 101682. doi: 10.1016/j.canep.2020.101682
[10] Li X, Cao X, Yang Y, et al. Human Papillomavirus awareness and vaccine acceptability among men who have sex with men from mainland China[J]. Sci Rep, 2019, 9(1): 8763. doi: 10.1038/s41598-019-45258-0
[11] 贾鑫华, 许琪, 杨红, 等. 赣州市女大学生对HPV及其疫苗的认知情况与接种意愿调查分析[J]. 实用临床医学, 2019, 20(3): 86-90, 102. https://www.cnki.com.cn/Article/CJFDTOTAL-LCSY201903031.htm [Jia XH, Xu Q, Yang H, et al. An Investigation on HPV Cognition Status and Vaccination Intention of Female College Students in Ganzhou[J]. Shi Yong Lin Chuang Yi Xue, 2019, 20(3): 86-90, 102. ] https://www.cnki.com.cn/Article/CJFDTOTAL-LCSY201903031.htm
[12] 陈慧, 张荣, 刘春容, 等. 我国西部地区城市和农村中学生对人乳头瘤病毒及其预防性疫苗的认知及态度调查[J]. 现代预防医学, 2020, 47(13): 2400-2404. https://www.cnki.com.cn/Article/CJFDTOTAL-XDYF202013024.htm [Chen H, Zhang R, Liu CR, et al. Knowledge and attitudes towards HPV and its vaccines among junior middle school students in urban and rural schools in Western China[J]. Xian Dai Yu Fang Yi Xue, 2020, 47(13): 2400-2404. ] https://www.cnki.com.cn/Article/CJFDTOTAL-XDYF202013024.htm
[13] 徐佳薇, 王青, 杨琳. 重庆市儿童母亲人乳头瘤病毒疫苗接种意愿和影响因素研究[J]. 中国疫苗和免疫, 2019, 25(3): 299-302. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGJM201903015.htm [Xu JW, Wang Q, Yang L. Acceptance of human papillomavirus (HPV) vaccine and its influencing factors among children' s mothers of Chongqing city[J]. Zhongguo Yi Miao He Mian Yi, 2019, 25(3): 299-302. ] https://www.cnki.com.cn/Article/CJFDTOTAL-ZGJM201903015.htm
[14] 刘春容, 蒲晨. 四川省某地农村女性对人乳头瘤病毒(HPV)预防性疫苗的认知及接种意愿调查[J]. 现代预防医学, 2019, 46(8): 1404-1407. https://www.cnki.com.cn/Article/CJFDTOTAL-XDYF201908015.htm [Liu CR, Pu C. Investigation on women' s awareness of human papillomavirus (HPV) preventive vaccine and their willingness to vaccinate in a rural area of Sichuan Province[J]. Xian Dai Yu Fang Yi Xue, 2019, 46(8): 1404-1407. ] https://www.cnki.com.cn/Article/CJFDTOTAL-XDYF201908015.htm
[15] Tian T, Wang D, Papamichael C, et al. HPV vaccination acceptability among men who have sex with men in Urumqi, China[J]. Hum Vacc Immunother, 2019, 15(4): 1005-1012. doi: 10.1080/21645515.2018.1520591
[16] Liu CR, Liang H, Zhang X, et al. Effect of an educational intervention on HPV knowledge and attitudes towards HPV and its vaccines among junior middle school students in Chengdu, China[J]. BMC Public Health, 2019, 19(1): 488. doi: 10.1186/s12889-019-6823-0
[17] Liu Y, Jiang X, Xu L, et al. Difference Between Medical and Nonmedical Students on Knowledge, Practice, and Attitude Towards the Human Papillomavirus Vaccine in China: a Cross-Sectional Study[J]. J Cancer Educ, 2021, 36(5): 1014-1021. doi: 10.1007/s13187-019-01682-4
[18] Ma QF, Guo YL, Yan B, et al. The Changes in the Awareness of Cervical Cancer Prevention and the Acceptability of HPV Vaccines among Women after Their Introduction in China[J]. Biomed Environ Sci, 2019, 32(11): 864-868.
[19] Chen AC, Astroth C, Reifsnider E, et al. Exploring Chinese College Students' HPV Awareness, Knowledge, Attitudes, and Intent of HPV Vaccination: a Qualitative Study[J]. J Cancer Educ, 2020, 4(20): 112-119.
[20] Zou H, Wang W, Ma Y, et al. How university students view human papillomavirus (HPV) vaccination: A cross-sectional study in Jinan, China[J]. Hum Vaccin Immunother, 2016, 12(1): 39-46. doi: 10.1080/21645515.2015.1072667
[21] 张华, 杨中华, 曹芹, 等. 2019年某地女教师人乳头瘤病毒及其疫苗知晓率及接种意愿调查[J]. 江苏预防医学, 2020, 31(5): 592-593. https://www.cnki.com.cn/Article/CJFDTOTAL-JSYF202005047.htm [Zhang H, Yang ZH, Cao Q, et al. Investigation on awareness rate and vaccination intention of human papillomavirus and its vaccine among female teachers in a certain place in 2019[J]. Jiangsu Yu Fang Yi Xue, 2020, 31(5): 592-593. ] https://www.cnki.com.cn/Article/CJFDTOTAL-JSYF202005047.htm
[22] 马昕玥, 蒋静, 汤月芳, 等. 广州市高校女大学生人乳头瘤病毒疫苗接种意愿和影响因素调查[J]. 中国妇幼保健, 2020, 35(24): 4820-4823. https://www.cnki.com.cn/Article/CJFDTOTAL-ZFYB202024058.htm [Ma XY, Jiang J, Tang YF, et al. Investigation on HPV vaccination willingness and influencing factors among female college students in Guangzhou[J]. Zhongguo Fu You Jian Kang, 2020, 35(24): 4820-4823. ] https://www.cnki.com.cn/Article/CJFDTOTAL-ZFYB202024058.htm
[23] 黄玲, 黄良玉, 卓霞, 等. 海口市0~6岁儿童母亲人乳头瘤病毒疫苗接种意愿及影响因素分析[J]. 实用预防医学, 2020, 27(11): 1358-1360. doi: 10.3969/j.issn.1006-3110.2020.11.020 [Huang L, Huang LY, Zhuo X, et al. Analysis of human papillomavirus vaccination willingness and influencing factors of mothers of children aged 0-6 in Haikou[J]. Shi Yong Yu Fang Yi Xue, 2020, 27(11): 1358-1360. ] doi: 10.3969/j.issn.1006-3110.2020.11.020
[24] 何佳露, 洪琳佳, 刘垚鑫, 等. 杭州9~14岁女童家长对HPV及疫苗认知和接种意愿调查[J]. 中国公共卫生, 2020, 36(10): 1478-1481. doi: 10.11847/zgggws1124125 [He JL, Hong LJ, Liu YX, et al. Knowledge about human papillomavirus (HPV) and HPV vaccine and willingness for their children' s vaccination among parents of 9-14 years old girls in Hangzhou city[J]. Zhongguo Gong Gong Wei Sheng, 2020, 36(10): 1478-1481. ] doi: 10.11847/zgggws1124125
[25] 孟凡莉, 宋凤斌, 叶佳瑶, 等. 杭州女大学生人乳头瘤病毒及疫苗认知与接种意愿[J]. 中国学校卫生, 2020, 41(11): 1737-1741. https://www.cnki.com.cn/Article/CJFDTOTAL-XIWS202011039.htm [Meng FL, Song FB, Ye JY, et al. Human papillomavirus and vaccine awareness and vaccination intention of female college students in Hangzhou[J]. Zhongguo Xue Xiao Wei Sheng, 2020, 41(11): 1737-1741. ] https://www.cnki.com.cn/Article/CJFDTOTAL-XIWS202011039.htm
[26] 张颂, 岳和欣, 任继禹, 等. 济宁市某高校在校生HPV疫苗接种意愿及影响因素[J]. 中国校医, 2020, 34(11): 801-804, 877. https://www.cnki.com.cn/Article/CJFDTOTAL-XIYI202011002.htm [Zhang S, Yue HX, Ren JY, et al. Investigation of intention of HPV vaccination and influencing factors among college students in Jining City[J]. Zhongguo Xiao Yi, 2020, 34(11): 801-804, 877. ] https://www.cnki.com.cn/Article/CJFDTOTAL-XIYI202011002.htm
[27] 周静, 李静, 马剑桥, 等. 健康教育对四川省医务人员HPV及其疫苗认知及态度的影响[J]. 现代预防医学, 2020, 47(20): 3764-3768. https://www.cnki.com.cn/Article/CJFDTOTAL-XDYF202020031.htm [Zhou J, Li J, Ma JQ, et al. Effect of health education on knowledge and attitude of HPV and its vaccines among healthcare professionals in, Sichuan province[J]. Xian Dai Yu Fang Yi Xue, 2020, 47(20): 3764-3768. ] https://www.cnki.com.cn/Article/CJFDTOTAL-XDYF202020031.htm
[28] 欧阳礼辰, 汪诗琪, 胡美玲, 等. 江汉大学女医学生对HPV及其疫苗的认知及接种意愿调查[J]. 江汉大学学报(自然科学版), 2020, 48(5): 47-54. https://www.cnki.com.cn/Article/CJFDTOTAL-WHZG202005006.htm [Ouyang LC, Wang SQ, Hu ML, et al. Investigation on Cognition and Vaccination Willingness of Female Medical Students of Jianghan University on HPV and HPV Vaccine[J]. Jianghan Da Xue Xue Bao(Zi Ran Ke Xue Ban), 2020, 48(5): 47-54. ] https://www.cnki.com.cn/Article/CJFDTOTAL-WHZG202005006.htm
[29] 邵海枫, 杜国明, 邹艳, 等. 江苏省张家港市成人女性对HPV及其疫苗的认知状况及影响因素[J]. 医学动物防制, 2020, 36(2): 171-174. https://www.cnki.com.cn/Article/CJFDTOTAL-YXDZ202002022.htm [Shao HF, Du GM, Zou Y, et al. Cognitive status and influencing factors of HPV and its vaccine in adult women in Zhangjiagang City of Jiangsu Province[J]. Yi Xue Dong Wu Fang Zhi, 2020, 36(2): 171-174. ] https://www.cnki.com.cn/Article/CJFDTOTAL-YXDZ202002022.htm
[30] 任文静, 高静, 呼琴琴. 男性护士对HPV疫苗接种和推荐意愿及其影响因素分析[J]. 中国病毒病杂志, 2020, 10(3): 204-208. https://www.cnki.com.cn/Article/CJFDTOTAL-ZRYX202003009.htm [Ren WJ, Gao J, Hu QQ. Influencing factors of the willingness of male nurses to HPV vaccination[J]. Zhongguo Bing Du Bing Za Zhi, 2020, 10(3): 204-208. ] https://www.cnki.com.cn/Article/CJFDTOTAL-ZRYX202003009.htm
[31] 赵晨宇, 朱浩, 郑娅楠, 等. 内蒙古高校学生人乳头瘤病毒疫苗接种意愿和影响因素调查[J]. 中国疫苗和免疫, 2020, 26(1): 71-75. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGJM202001016.htm [Zhao CY, Zhu H, Zheng YN, et al. Investigation on human papillomavirus vaccination willingness and influencing factors of college students in Inner Mongolia[J]. Zhongguo Yi Miao He Mian Yi, 2020, 26(1): 71-75. ] https://www.cnki.com.cn/Article/CJFDTOTAL-ZGJM202001016.htm
[32] 刘凯燕, 郭玮玮, 刘淑敏. 宁夏高校护生对HPV疫苗的认知及接种意愿调查分析[J]. 卫生职业教育, 2020, 38(12): 104-106. https://www.cnki.com.cn/Article/CJFDTOTAL-ZDYX202012053.htm [Liu KY, Guo WW Liu SM. Investigation and analysis of nursing students' cognition of HPV vaccine and vaccination willingness in Colleges and universities in Ningxia[J]. Wei Sheng Zhi Ye Jiao Yu, 2020, 38(12): 104-106. ] https://www.cnki.com.cn/Article/CJFDTOTAL-ZDYX202012053.htm
[33] 徐帅师, 聂文佳, 王小楠, 等. 石家庄市某高校大学生对HPV相关知识认知及态度调查[J]. 肿瘤预防与治疗, 2019, 32(10): 920-924. doi: 10.3969/j.issn.1674-0904.2019.10.010 [Xu SS, Nie WJ, Wang XN, et al. Investigation on knowledge and attitude towards HPV among college students in Shijiazhuang[J]. Zhong Liu Yu Fang Yu Zhi Liao, 2019, 32(10): 920-924. ] doi: 10.3969/j.issn.1674-0904.2019.10.010
[34] He J, He L. Knowledge of HPV and acceptability of HPV vaccine among women in western China: a cross-sectional survey[J]. BMC Womens Health, 2018, 18(1): 130. doi: 10.1186/s12905-018-0619-8
[35] 陈鹏, 姜珊, 李冰洋, 等. 烟台高校学生对宫颈癌及HPV疫苗的认知情况的调查[J]. 现代预防医学, 2019, 46(13): 2466-2469, 2487. https://www.cnki.com.cn/Article/CJFDTOTAL-XDYF201913038.htm [Chen P, Jiang S, Li BY, et al. Cognition of HPV and its vaccine among college students, Yantai[J]. Xian Dai Yu Fang Yi Xue, 2019, 46(13): 2466-2469, 2487. ] https://www.cnki.com.cn/Article/CJFDTOTAL-XDYF201913038.htm
[36] 史金晶, 张肖肖, 郑徽, 等. 中国大陆青少年家长人乳头瘤病毒疫苗认知度和接受度Meta分析[J]. 中国疫苗和免疫, 2019, 25(4): 464-470. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGJM201904025.htm [Shi JJ, Zhang XX, Zheng H, et al. Awareness and acceptance of human papillomavirus vaccine among parents of adolescents in Chinese mainland: a meta-analysis[J]. Zhongguo Yi Miao He Mian Yi, 2019, 25(4): 464-470. ] https://www.cnki.com.cn/Article/CJFDTOTAL-ZGJM201904025.htm
[37] 梁铭康, 张瑞航, 达娃曲珍, 等. 拉萨市高校女性大学生对HPV疫苗的认知及接种意愿[J]. 西藏医药, 2021, 42(2): 85-88. https://www.cnki.com.cn/Article/CJFDTOTAL-XZYY202102039.htm [Liang MK, Zhang RH, DaWa QZ, et al. Cognition of HPV vaccine and vaccination willingness of female college students in Lhasa[J]. Xizang Yi Yao, 2021, 42(2): 85-88. ] https://www.cnki.com.cn/Article/CJFDTOTAL-XZYY202102039.htm
[38] 王晓妮, 宁超, 李海龙, 等. 西安市民办高校大学生HPV相关核心知识知晓现状及其影响因素[J]. 中国艾滋病性病, 2021, 27(2): 159-163. https://www.cnki.com.cn/Article/CJFDTOTAL-XBYA202102012.htm [Wang XN, Ning C, Li HL, et al. The current status and influencing factors of HPV related core knowledge of college students in xi' an private universities[J]. Zhongguo Ai Zi Bing Xing Bing, 2021, 27(2): 159-163. ] https://www.cnki.com.cn/Article/CJFDTOTAL-XBYA202102012.htm
[39] 郭凤芝. 浙江省金华市女性对接种HPV疫苗的认知和接种意愿调查分析[J]. 中国乡村医药, 2021, 28(2): 38-39. https://www.cnki.com.cn/Article/CJFDTOTAL-XCYY202102025.htm [Guo FZ. Investigation and analysis of women' s cognition and willingness to vaccinate HPV vaccine in Jinhua City, Zhejiang Province[J]. Zhongguo Xiang Cun Yi Yao, 2021, 28(2): 38-39. ] https://www.cnki.com.cn/Article/CJFDTOTAL-XCYY202102025.htm
[40] 农秋锋. 宫颈癌疫苗及其应用研究进展[J]. 内科, 2020, 15(1): 57-59. https://www.cnki.com.cn/Article/CJFDTOTAL-NKYT202001022.htm [Nong QF. Research progress of cervical cancer vaccine and its application[J]. Nei Ke, 2020, 15(1): 57-59. ] https://www.cnki.com.cn/Article/CJFDTOTAL-NKYT202001022.htm