Investigating Factors Affecting the Effectiveness of Gardasil 4, Cervarix, and Gardasil 9 Vaccines Considering the Who Regions in Females: A Systematic Review Publisher Pubmed



Zadeh Mehrizi T¹ ; Ataeipirkooh A^{1, 2, 3} ; Eshrati B^{1, 4, 5} ; Ebrahimi Shahmabadi H⁸ Show Affiliations
Source: Cancer Epidemiology Published:2025

Abstract

Background: Currently, the best method for preventing Human Papilloma Virus (HPV) infection is vaccination. The present systematic review aims to review the latest findings on the factors affecting the efficacy of Gardasil 4, Cervarix, and Gardasil-9 vaccines on reducing pregenital lesions and reducing high-risk genotypes of cervical cancer in females aged 9–45 years and to examine the distribution of studies conducted in this regard in regions. In this study only the names of the vaccines were used and the vaccines were examined only according to the name. The name of WHO is only used to imply the distribution and access to health services in the world and not in terms of the vaccine approval in different organizations. Methods: A search for each vaccine was performed using PubMed, Scopus, and Web of Science. Five hundred and forty, 257, and 191 unique studies were obtained from the aforementioned databases for Gardasil 4, Cervarix, and Gardasil 9 vaccines, respectively. After applying the inclusion and exclusion criteria, 17 studies on Gardasil 4, seven studies on Cervarix, and two studies on Gardasil 9 were reviewed. Results: This study indicated that within various regions of the WHO, comprehensive effectiveness studies have not been conducted, and specifically within the Eastern Mediterranean Region (EMR) and South-East Asia Region (SEAR), no effectiveness studies have been recorded. Consequently, these regions necessitate the execution of effectiveness studies. Therefore, it is advisable to undertake investigations regarding the effectiveness of papillomavirus vaccination in the EMR and SEAR regions as delineated by the WHO. Moreover, it was demonstrated that in diverse nations, an array of factors such as age, gender, prevalent genotypes within the population, culture, the age at sexual activity initiation, the healthcare infrastructure, and timely screening can significantly impact the effectiveness of the vaccine. Furthermore, in nations with suboptimal vaccination coverage, a robust healthcare system coupled with the implementation of specialized testing and prompt follow-up can substantially aid in cancer prevention. The outcomes of this investigation confirm the administration of at least one dose of the vaccination. It reveals that in the absence of vaccination, a stringent healthcare system may contribute to the reduction of cervical cancer incidence. Additionally, in these nations, enhancements in healthcare systems, screening protocols, and public awareness play a crucial role in augmenting vaccination effectiveness. Collectively, a lower age at the time of vaccination (9–15 years), reduced sexual exposure prior to vaccination, vaccination prior to the onset of precancerous lesions, and adherence to the recommended vaccination schedule are associated with heightened vaccine effectiveness. Furthermore, the effectiveness of the vaccination dose is age-dependent, as one dose can be effective for individuals aged 15 years or younger. Conclusions: Various factors, including age, sex, common genotypes in population, culture, age at sexual initiation, healthcare system, and screening at recommended time, can play a significant role in vaccine effectiveness. Additionally, it is suggested that in the developing countries, a single dose vaccination program is sufficient for children aged 15 years or younger. Also in these countries, improving the care system, screening system, and awareness play a significant role in enhancing the effectiveness of vaccination. It is also recommended that studies on the effectiveness of the papilloma vaccination in the EMR and SEAR regions covered by the WHO to be conducted. According to the inclusion criteria, all countries were included in the study; thus, the effects of the individual's genotype, which depends on the geographical region, can affect the vaccine effectiveness. Individuals aged 9–45 who can receive the vaccine according to the guidelines, were included in the study. Age is one of the factors affecting the vaccine effectiveness. Also, according to the policies of healthcare organizations, including the Ministries of Health of countries, various health services are provided in different geographical regions. Therefore, females's access to the vaccine occurs at different ages, and the effectiveness of the vaccine decreases by increasing the age at which the vaccine is received. Countries with poor healthcare system have less access to the vaccine, which can affect the effectiveness of the vaccine and herd immunity. © 2025