基于层次-K 均值混合聚类法的中国人乳头瘤病毒疫苗双边国际合作优先程度评估

Evaluation of bilateral vaccine cooperation priority countries on Chinese human papillomavirus vaccine using hierarchical K-means hybrid clustering

摘要

目的：评估中国人乳头瘤病毒（human papillomavirus，HPV）疫苗双边国际合作中的优先国家及对应的合作方式，为优化中国的 HPV 疫苗合作策略提供参考与借鉴。方法：借助已建立完成的中国国际疫苗合作优先国家篮选指标体系，使用加权评分法对处于全球疫苗免疫联盟第三、第四援助阶段29个国家的 HPV 疫苗合作优先程度进行评分和排序。基于一级指标得分情况运用层次聚类和 K 均值聚类结合的层次-K 均值混合聚类法进行分析。结果：评分排序中，排名前 10 的国家大多为亚洲国家，非洲国家排名较靠后。29 个国家在 HPV 疫苗合作中可分为 3 个类别：技术转移优先型、基础援助型、高壁垒潜力型。技术转移优先型国家有 3 个，为印度尼西亚、越南和乌兹别克斯坦，该类别在经济、科技和政治因素上得分较高，有良好的支付能力和疫苗进口规模，具有一定的疫苗研发、生产能力，政治稳定性较强，推荐优先开展合作；基础援助型国家有25个，各因素得分接近平均水平，多为人口较少或低收入国家，适合通过援助和优惠采购开展合作；高壁垒潜力型国家有1个，为印度，其在社会因素和科技因素上得分较高，但法律及规章因素得分极低，提示 HPV 疫苗需求量大，具有成规模的疫苗产业基础，疫苗产品注册壁垒高，开展合作难度大。建议与印度尼西亚开展优惠价格成品出口、疫苗临床试验方面的合作，同时探索授权生产、技术转移的合作；与越南开展疫苗临床试验的合作；与乌兹别克斯坦开展授权生产、技术转移方面的合作。结论：中国开展 HPV 疫苗双边国际合作的优先国家为印度尼西亚、越南和乌兹别克斯坦这类技术转移优先型国家，应以涵盖成品出口、临床试验、授权生产与技术转移的方式与其开展合作。

Abstract

Objective：To evaluate priority target countries and formulate context-specific cooperation modalities for China＇s bilateral international collaboration on human papillomavirus（HPV）vaccines， thereby furnishing an evidence-based reference for optimizing China＇s bilateral vaccine cooperation stra-tegies and contributing to global health equity. Methods：Using a previously established index system de- signed for selecting preferred countries in China＇s international vaccine cooperation，we comprehensively applied a weighted-scoring approach to quantitatively rank 29 Phases 3 and 4 Global Alliance for Vaccines and Immunization（Gavi）eligible countries in HPV vaccine cooperation.Based on 5 first-level index （legal and regulatory factors，economic factors，political factors，social factors，and technological fac- tors）scores，a hierarchical K-means hybrid method was used for clustering the countries.Hierarchical clustering was initially utilized to explore the underlying data structure and determine the optimal number of clusters，followed by K-means clustering to precisely categorize the evaluated nations based on their multidimensional characteristics. Results：The top10 countries were mostly Asian countries.African countries were mostly in the lower ranks.The countries were clustered into three types：（1）Technology transfer priority（n=3 ：Indonesia，Viet Nam，Uzbekistan），characterized by above-average economic， techno-scientific and political scores，robust vaccine-import volumes，non-negligible domestic manufac- turing capacity and high political stability-recommended for priority collaboration；（2）Basic assistance (n=25) ，approximating mean indicator values，typically low-population or low-income economies sui-table for aid-based or concessional-procurement models；（3）High barrier (n=1 ：India），exhibiting high socio-demographic and scientific base yet minimal legal-regulatory scores，indicating large demand， established vaccine industry，but formidable registration barriers.Policy recommendations included：con- cessional product export plus clinical-trial cooperation with Indonesia，with prospective licensing and technology transfer；clinical-trial collaboration with Viet Nam；and licensing/technology-transfer schemes with Uzbekistan. Conclusion：Indonesia，Viet Nam，and Uzbekistan are identified as the priority target countries for China＇s bilateral international cooperation on HPV vaccines.For these technology-transfer priority nations，cooperation should be strategically conducted through diverse mo- dalities encompassing vaccine product export，clinical trial collaboration，authorized licensing，and technology transfer.

关键词

国际合作 / 人乳头瘤病毒疫苗 / 聚类分析 / 层次聚类 / K 均值聚类

Key words

International cooperation / Human papillomavirus vaccine / Cluster analysis / Hierarchical clustering / K-means clustering

参考文献

[1] de Martel C, Georges D, Bray F, et al. Global burden of cancer attributable to infections in 2018:A worldwide incidence analysis[J]. Lancet Glob Health, 2020, 8 (2):e180-e190.

[2] World Health Organization. Global strategy to accelerate the elimi- nation of cervical cancer as a public health problem[R]. Geneva: World Health Organization, 2020.

[3] Dorji T, Nopsopon T, Tamang ST, et al. Human papillomavirus vaccination uptake in low-and middle-income countries:A meta- analysis[J]. EClinicalMedicine, 2021, 34: 100836.

[4] Cernuschi T, Gaglione S, Bozzani F. Challenges to sustainable immunization systems in Gavi transitioning countries[J]. Vac- cine, 2018, 36(45):6858-6866.

[5] Li AJ, Kyesi F, Mwengee W, et al. Impact of the human papillo- mavirus(HPV)vaccine supply shortage on Tanzania＇s national HPV vaccine introduction[J]. Vaccine,2022,40:A26-A29.

[6] Wu T, Hu YM, Li J, et al. Immunogenicity and safety of an E.coli-produced bivalent human papillomavirus(type 16 and 18) vaccine:A randomized controlled phase 2 clinical trial[J]. Vac- cine, 2015, 33(32):3940-3946.

[7] Zhu FC, Zhong GH, Huang WJ, et al. Head-to-head immuno- genicity comparison of an Escherichia coli-produced 9-valent hu- man papillomavirus vaccine and Gardasil 9 in women aged 18-26 years in China:A randomised blinded clinical trial[J]. Lancet Infect Dis, 2023, 23(11):1313-1322.

[8] Li J, Shi LW, Li K, et al. Comparison of the safety and persis- tence of immunogenicity of bivalent HPV16/18 vaccine in healthy 9-14-year-old and 18-26-year-old Chinese females:A rando-mized,double-blind,non-inferiority clinical trial[J]. Vaccine, 2023, 41(48):7212-7219.

[9] Bown CP, Snyder CM, Staiger RW. Vaccine supply chain resi-lience and international cooperation[R]. Hanover: Dartmouth College Economics Department, 2022.

[10] Pratiwi FI, Muttaqien M, Samy M, et al. International cooperation during COVID-19:Case study vaccine cooperation and its impact in Indonesia[J]. Asian Polit Policy, 2022, 14(3):403-422.

[11] Sirleaf EJ, Clark H. Achieving vaccination justice:A call for global cooperation[J]. PLoS Glob Public Health, 2021, 1(10): e0000036.

[12] 吴音格, 崔宇煊, 黄旸木. 中国国际疫苗合作优先国家篮选指标体系构建研究[J]. 中国卫生政策研究, 2024, 17(9):60-67.

[13] 王谋, 康文梅, 张莹. 应对气候变化南南合作优先合作国家选择方法探讨[J]. 气候变化研究进展, 2021, 17(6):744-751.

[14] 王怀豫, 肖尧, 李奕辰, 等. ＂一带一路＂建设背景下中国与东盟国家农业科技合作的选择机制[J]. 科技管理研究, 2022, 42(16):35-44.

[15] Peterson AD, Ghosh AP, Maitra R. Merging K-means with hierar-chical clustering for identifying general-shaped groups[J]. Stat (Int Stat Inst), 2018, 7(1):el72.

[16] Chen TS, Tsai TH, Chen YT, et al. A combined K-means and hierarchical clustering method for improving the clustering efficien-cy of microarray[C]// 2005 International Symposium on Intelligent Signal Processing and Communication Systems.Piscataway, USA: IEEE, 2006:405-408.

[17] Gavi. Eligibility＆Co-financing policies[EB/OL].( 2025-06-18) [ 2025-09-15].

[18] 李文超, 周勇, 夏士雄. 一种新的基于层次和 K-means 方法的聚类算法[C]// 第二十六届中国控制会议论文集. 张家界: 中国自动化学会控制理论专业委员会, 2007:2331-2335.

[19] 胡伟. 改进的层次 K 均值聚类算法[J]. 计算机工程与应用, 2013, 49(2):157-159.

[20] World Health Organization.IA 2030 Global Report 2024 [EB/OL]. (2025-04-26)[ 2025-09-15].

[21] Ver AT, Notarte KI, Velasco JV, et al. A systematic review of the barriers to implementing human papillomavirus vaccination pro-grams in low-and middle-income countries in the Asia-Pacific[J]. Asia Pac J Clin Oncol, 2021, 17(6):530-545.

[22] Gallagher KE, Howard N, Kabakama S, et al. Human papilloma-virus(HPV)vaccine coverage achievements in low and middle-income countries 2007-2016[J]. Papillomavirus Res, 2017, 4: 72-78.

[23] Kurniawati E, Madu L. Indonesia＇s efforts to overcome COVID-19 pandemic through international cooperation[C]// Proceedings of the RSF conference series: Business,management and social sciences. Bandung, Indonesia: Research Synergy Foundation, 2021:242-246.

[24] Yeremia AE, Raditio KH. Indonesia-China vaccine cooperationand South China Sea diplomacy[J]. ISEAS Perspective, 2021 (55):1-15.

[25] MSD in Indonesia. MSD and Bio Farma sign a framework agree- ment for technology transfer partnership to locally manufacture hu- man papillomavirus(HPV)vaccine in Indonesia[EB/OL]. (2022-12-13)[ 2025-09-15]. of％20HPV％20vaccine％ 20 in％20Indonesia.

[26] Setiawan D, Ramadani P, Lianawati L, et al. HPV vaccination program in Indonesia:Effectiveness,dose,scale-up costs,future prospects,and policy recommendations[J]. Asian Pac J Cancer Prev, 2025, 26(2):421-434.

[27] Drolet M, Laprise JF, Martin D, et al. Optimal human papilloma- virus vaccination strategies to prevent cervical cancer in low-income and middle-income countries in the context of limited resources:A mathematical modelling analysis[J]. Lancet Infect Dis, 2021, 21 (11):1598-1610.

[28] Le XTT, Nguyen PTN, Do TTT, et al. Intention to pay for HPV vaccination among women of childbearing age in Vietnam[J]. Int J Environ Res Public Health, 2020, 17(9): 3144.

[29] World Health Organization. WHO adds an HPV vaccine for single- dose use[EB/OL]. (2024-10-04)[2025-09-15].

[30] Gavi. Detailed product profiles[EB/OL]. (2025-07-13)[2025- 09-15].

[31] van Dijk RJL, Lo CY. The effect of Chinese vaccine diplomacy during COVID-19 in the Philippines and Vietnam:A multiple case study from a soft power perspective[J]. Humanit Soc Sci Commun, 2023, 10: 687.

[32] Badur S, Ota M, Öztürk S, et al. Vaccine confidence:The keys to restoring trust[J]. Hum Vaccines Immunother, 2020, 16(5): 1007-1017.

[33] Ussai S, Seyidov T, Khomasuridze T, et al. Regional alliance for cervical cancer prevention in eastern Europe and central Asia:Pro- gressing towards the target 1 of the global strategy for cervical can- cer elimination[J]. Healthcare, 2025, 13(10): 1209.

[34] Filipović A. China, Vaccine diplomacy of the United States, In- dia,and Russia during the COVID-19 pandemic:A comparative analysis[J]. Međunarodna politika, 2024, 75(1190):57-90.

[35] Yan Q, Abdurakhmonov IY, Cao J. Cooperation and innovation: An interview with Minister Ibrokhim Y.Abdurakhmonov and Pro- fessor Jinghua Cao[J]. hLife, 2024, 2(11):547-553.

[36] UNICEF.Gavi Shipments 2025 Plan-Vaccines＆Devices-All Regions[EB/OL]. (2025-08-28)[ 2025-09-15].

基金资助

国家自然科学基金与盖茨基金联合资助项目(72361127504-2023YFVA1003)