子宮頸癌疫苗接種策略與孕婦垂直傳染防治之評估與探討

HPV vaccination implantation strategy associated with maternal vertical transmission

丁雅飛(Ting,YA-FEY)

指導教授 ： 陳秀熙

國立臺灣大學/公共衛生學院/公共衛生碩士學位學程/碩士(2020年)

https://doi.org/10.6342/NTU202000632

摘要

摘要:
目的：概述HPV疫苗的目前成效,以及了解是否可預防母性(maternal)感染後的相關併發症。
背景:目前已知HPV對女性有著非常大的健康影響，WHO也提出建議各國採取疫苗施打的預防政策，但疫苗是否能有效預防孕婦感染HPV帶來的危險，或者能否預防對胎兒的健康不良影響。目前還未系統性的回顧或廣泛的理解。
研究設計和方法：採用綜合審查(integrative review)，利用Google學術及Airiti Library華藝線上圖書館，檢索HPV疫苗成效及HPV垂直感染的相關文獻 ，閱讀論文的研究主題及目的，決定是否納入研究文獻，最終將收納的文章閱讀後，進行分析，分類摘要信息。
結果：總共116篇相關的文獻,在排除無全文的文章及滴蟲或HIVD垂直感染的文獻,納入共14篇HPV疫苗成效的文章及10篇HPV垂直感染的文獻。
目前HPV疫苗施打成效上，針對女孩(12歲)施打二價疫苗具有保護及健康/成本效益。(2009美國,2014挪威,2015高收入國家, 2017德國,2019台灣。) 而男孩施打二價疫苗,幾篇研究都顯示無明確的成本效益(2009美國, 2015高收入國家) ,除非疫苗價格低於$36/劑(2014挪威)。而在疫苗安全上，在芬蘭的14838名的受試者,二價HPV疫苗與B型肝炎疫苗(HBV)相比，沒有觀察到不良反應及自身免疫疾病增加的現象。而四價HPV疫苗及九價疫苗分別有相關研究證明，疫苗具有致免疫性的效果 (2007 十個國家及2019德國) 。但由於九價的疫苗的本較高，並未顯示出具成本效益 (2016德國, 2018高收入國家)。
而在母性感染HPV對胎兒的影響方面, 研究結果證明懷孕期間具有垂直傳染給胎兒的情形(Lee, Park, Norwitz et al. 2013, Freitas, Mariz, Silva et al. 2014, Ambühl, Baandrup, Dybkær et al. 2016 , Mariusz Skoczyński1 et al.2019) 。而垂直感染的影響下與足月妊娠的孕婦相比,孕婦自然流產及早產機率是明確更高的(LeaMariaMargareta Ambühl et al. 2016)。影響還有子宮內生長遲滯(IUGR)胎兒體重過輕的情形(Judith Helen Ford et al.2019)。新生兒出生感染HPV除了與母親為HPV陽性一致性相關，研究也發現家庭成員及父親感染HPV也會導致新生兒感染HPV的風險增加，包含胎兒眼瞼、口腔HPV (Sasidharanpillai Sabeena et al. 2017, Mariusz Skoczyński et al. 2019)。另外,也有研究證明,陰道分娩的新生兒其垂直感染的情形,明顯高於剖腹產。(Ulla Bonde, et al. 2014 , K. Chatzistamatiou al. 2016)。在疫苗與預防垂直感染的成效上，Smith, Parker, Rubenstein et al. (2010)的研究檢測婦女懷孕前使用口服HPV疫苗，不能有效預防垂直感染。但Ulla Bonde 在2014年的研究，觀察38190名接種HPV疫苗的孕婦,其胎兒分娩時臍帶血具有HPV疫苗的抗體,而提供防止HPV傳染得保護力。
結論：證實了人類乳突病毒不僅對女性帶來極大的健康影響，甚至對對胎兒都造成了重大的危害風險。早期預防是公共衛生上非常重要的健康預防措施，期待未來有更多的大型實證研究,以得出母性疫苗接種是否確實能預防胎兒HPV的垂直感染的答案。

關鍵字

人類乳突病毒 ； 垂直感染 ； 流產 ； HPV 垂直感染 ； 孕期感染 ； 成本效益 ； 疫苗接種

並列摘要

Abstract
Objective: To describe the effectiveness of HPV vaccine thus far and understand whether it can prevent infant from maternal infection and relevant complications
Background: Effects of HPV on the health of female have known and recommendations from WHO have delivered to implement vaccine prevention policy, the effective prevention to the jeopardies of HPV infection of pregnant female and the health of embryo and fetus are still unclear without systematic review and comprehension.
Research design and method: By using integrative review such as Google scholar and Airiti Library, searching relevant studies about the outcomes of HPV vaccine and Vertical HPV Transmission, and then to determine whether they can be adopted by comprehensive reading. Later, analyzing those selected studies and categorizing key information.
Results: Within 116 studies, 14 HPV vaccine outcome studies and 10 Vertical HPV Transmission studies are adopted, excluding trichomonas or HIVD vertical infection.
Recently the outcome of bivalent HPV vaccine to protection and health/cost effectiveness is significantly positive for 12y girl (US, 2009; Norway, 2014; high income states, 2015; Germany, 2017; Taiwan, 2019) whereas there is no significantly positive cost effectiveness for boy (US, 2009; high income states, 2015) unless the prices of HPV vaccine are under $36 per dose (Norway, 2014). For the safety of vaccine, there is no negative reaction and increased autoimmune disease between bivalent HPV vaccine and HBV within 14838 examinees in Finland. As for tetravalent vaccine and nine-valent vaccine, studies prove they have significant immunogenic effect (ten states, 2007; Germany, 2019); however, there is no evidence to show the cost effectiveness due to the costs of nine-valent vaccine are high (Germany, 2016; high income states, 2018). As for maternal infection, evidences confirm the vertical infection during pregnancy (Lee, Park, Norwitz et al. 2013, Freitas, Mariz, Silva et al. 2014, Ambühl, Baandrup, Dybkær et al. 2016, Mariusz Skoczyński1 et al.2019), and by the effects of vertical infection, the ratios of miscarriage and premature are higher than full-term pregnancy (LeaMariaMargareta Ambühl et al. 2016). Furthermore, vertical infection can bring IUGR and underweight infant. Besides the HPV-infected newborn is correlated with its HPV positive mother, the HPV members of family and HPV father can also raise risks, including eyelid and oral HPV (Sasidharanpillai Sabeena et al. 2017, Mariusz Skoczyński et al. 2019). Moreover, newborn by vaginal birth is significantly infected higher than caesarean section (Ulla Bonde, et al. 2014, K. Chatzistamatiou al. 2016). In the effectiveness of vaccine on vertical infection prevention, Smith, Parker, Rubenstein et al. (2010) argued the effects of oral HPV vaccine are insignificant on vertical infection prevention for female before pregnancy. By observing 38190 females who have taken HPV vaccine, Bonde (2014) argued umbilical cord blood has antibodies to HPV vaccine to prevent HPV infection.
Conclusion: Affirmatively that human papillomavirus not only bring great negative effects on health but also jeopardize the safety of embryo, fetus, and infant. Early prevention indeed is a critical measure for public health and hoping relevant studies can answer whether HPV vaccine could prevent Vertical HPV Transmission in the future.

並列關鍵字

Human Papillomavirus ； HPV ； miscarriage ； Vertical HPV Transmission ； perinatal HPV transmission ； Cost-effectiveness ； vaccination.

參考文獻

1. Ambühl, L. M. M., Baandrup, U., Dybkær, K., Blaakær, J., Uldbjerg, N., & Sørensen, S. (2016). Human papillomavirus infection as a possible cause of spontaneous abortion and spontaneous preterm delivery. Infectious Diseases in Obstetrics and Gynecology, 2016, 1-19.

2. Bonde, U., Joergensen, J. S., Mogensen, O., & Lamont, R. F. (2014). The potential role of HPV vaccination in the prevention of infectious complications of pregnancy. Expert Review of Vaccines, 13(11), 1307-1316.

3. Burger, E. A., Sy, S., Nygård, M., Kristiansen, I. S., & Kim, J. J. (2014). Prevention of HPV-related cancers in Norway: cost-effectiveness of expanding the HPV vaccination program to include pre-adolescent boys. PloS One, 9(3), e89974.

4. Chatzistamatiou, K., Sotiriadis, A., & Agorastos, T. (2016). Effect of mode of delivery on vertical human papillomavirus transmission: a meta-analysis. Journal of Obstetrics and Gynecology, 36(1), 10-14.

5. Damm, O., Horn, J., Mikolajczyk, R. T., Kretzschmar, M. E., Kaufmann, A. M., Deleré, Y., ... & Greiner, W. (2017). Cost-effectiveness of human papillomavirus vaccination in Germany. Cost Effectiveness and Resource Allocation, 15(1), 18-37.