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Introduction
Human papillomavirus (HPV) is one of the most common sexually transmitted infections (STIs) in the world. Persistent infection with certain types of HPV can lead to cervical cancer, with around 530,000 new cases a year worldwide1. Despite being highly preventable, it is estimated that cervical cancer kills 35,700 women annually in the Americas, with 80% of deaths occurring in Latin America and the Caribbean. Rates in this region are three times higher than in North America2.
Immunization is one of the key strategies for preventing this type of cancer. In Brazil, the HPV quadrivalent vaccine was introduced into the National Immunization Program (PNI) in 2014 and is gradually being made available free of charge by the country\'s public health system, o Sistema Único de Saúde (SUS) or Unified Health System. Initially, in 2014, immunization targeted girls aged 11-13, being extended to cover the 9-13 age group in 2015, and then to girls and boys aged 14 and 11-15, respectively, in 20172-4.
However, HPV vaccination coverage is low in Brazil due to an array of factors, including low education and income levels, limited access to information and health services and obstacles such as religious beliefs5. A study on HPV vaccination in the Northeast of Brazil during the period 2013-2021 revealed that the state with the lowest coverage rates was Maranhão. In this sense, the spatial analysis of vaccination coverage using georeferencing techniques can contribute to a better understanding of the event studied⁶.
In light of the above, it is important to determine age- and gender-stratified vaccination coverage across the state to generate information that can be used to promote effective targeting of actions to encourage vaccination. The aim of this study was therefore to describe the spatial distribution of HPV vaccination coverage among girls and boys in the state of Maranhão.

Methods
We conducted a retrospective ecological study of HPV vaccination coverage in age cohorts of girls and boys living in Maranhão. The study units were the state’s 217 municipalities and 19 health regions7.
The study population consisted of all boys and girls living in the state during the study period. Vaccination data from the National Immunization Program (PNI/APIWEB) was obtained from a publicly available online database run by the SUS’s Department of Informatics (DATASUS). Population data from the 2010 national census (CD) were obtained from the Brazilian Institute of Geography and Statistics (IBGE) website. The data were collected in the second half of 2023. Vaccination records not containing information on municipality of residence were excluded, since this information is essential to carry out spatial analysis.
The vaccination data were disaggregated by age and sex and dose (first and second). Vaccination coverage was calculated using the methodology recommended by the PNI3, which is based on the total number of vaccine doses administered in each age cohort since the first year in which they became eligible for vaccination.
Each age cohort was made up of boys and girls born in the same year. Three cohorts were defined for the girls (1, 2 and 3), as follows: a) cohort 1 - aged 13 in 2021, who had the opportunity to be vaccinated at ages 9, 10, 11, 12 or 13 during the period 2017-2021; b) cohort 2 - aged 14 in 2021, who had the opportunity to be vaccinated at ages 10, 11, 12, 13 or 14 during the period 2017-2021; and c) cohort 3, aged 15 in 2021, who had the opportunity to be vaccinated at ages 11, 12, 13 or 14 during the period 2017-2021.
The following cohorts (1, 2 and 3) were defined for boys: a) cohort 1 - aged 16 in 2021, who had the opportunity to be vaccinated at the ages of 12, 13 and 14 during the period 2017-2019; b) cohort 2 - aged 17 in 2021, who had the opportunity to be vaccinated at the ages of 13 and 14 during the period 2017-2018; and c) cohort 3, aged 18 in 2021, who had the opportunity to be vaccinated at the age of 14 in 2017. Figure 1 summarizes the construction of the cohorts for girls and boys.

Based on the methodology recommended by the PNI3, vaccination coverage in girls was calculated using the total number of vaccine doses administered to each cohort as the numerator, and the number of girls living in each municipality aged 2, 3 and 4 in 2010 as the denominator. For boys, the denominator was the number of boys aged 5, 6 and 7 living in each municipality in Maranhão in 2010.
Vaccination coverage completeness was calculated based on the number of second doses of the vaccine administered to the selected cohorts in each year of the evaluation, where the numerator was the number of second doses administered and the denominator was the target population of the selected cohort, multiplied by 100. The following targets set by the PNI3 and calculated separately for the first and second dose were used to assess vaccination coverage: inadequate – under 80%; adequate – equal to or greater than 80%.
To analyze the spatial distribution of vaccination coverage, the information was georeferenced against the digital grid of the state of Maranhão using the IBGE basemap and spatialization maps built using QGIS version 3.22.
In accordance with National Health Council resolutions 466/2012 and 510/2016, the study did not require ethical approval as it was conducted using exclusively secondary data available in the public domain8.

Results
Vaccination coverage rates were highest in cohort 1 of girls and boys: girls: first dose - 86%; second dose - 67%.; boys, first dose - 68%; second dose - 31%. It is worth noting that in the girls in cohort 2, the second dose coverage rate was higher than the first dose coverage rate (Table 1).
Sixteen of the 19 health regions showed adequate first dose coverage among girls in cohort 1; however, second dose coverage in this cohort was adequate in only five regions (Caxias, Imperatriz, Pedreiras, Santa Inês and São João dos Patos). Among boys, only five regions showed adequate first dose coverage (Açailândia, Imperatriz, Pedreiras, Santa Inês and São Joao dos Patos) (Table 2).
With regard to coverage at municipal level, 131 of the state’s 217 municipalities showed adequate first dose coverage among girls in cohort 1. However, only two municipalities in cohort 2 and one in cohort 3 had adequate first dose coverage (Figure 2). With regard to the second dose, 70 municipalities in cohort 1 and 11 in cohort 2 achieved adequate coverage, with no municipalities attaining adequate coverage for cohort 3 (Figure 2).
Among boys, 83 municipalities in cohort 1 and 27 municipalities in cohort 2 achieved adequate first dose coverage, while no municipality attained adequate coverage for cohort 3. Only two municipalities obtained adequate second dose coverage, both in cohort 2 (Figure 3).

Discussion
The findings show that the implementation of HPV vaccination in Maranhão has faced challenges since its inception, failing to achieve adequate vaccination coverage across the two doses when assessed against the targets set by the PNI3. The results of the comparative analysis of the cohorts showed that coverage was higher in girls in both the first and second doses.
Some authors have reported higher than expected coverage in some age groups, especially at ages 10, 13 and 14. It is important to note that vaccination is influenced by parents\' understanding of HPV and its consequences for their children\'s health, especially in younger age groups. Factors that negatively influence vaccination include fear of adverse effects due to lack of knowledge about safety and health effects9-11.
Differences in vaccination coverage rates between girls and boys have been reported in the literature. One study showed that only 64.4% of parents of girls and 41.6% of parents of boys reported that they received a recommendation for the HPV vaccine from their clinician12. Another study also showed a higher percentage of unvaccinated boys and a positive association between being male and unawareness of the HPV campaign13.
In view of the above, stratifying rates by gender is important to gain a better understanding of vaccination coverage among children and adolescents, with the results of our study showing a lower percentage of vaccinated boys in comparison to girls. Interventions should therefore take gender differences into account when developing strategies to improve coverage. It is also important to highlight that second dose coverage was higher than first dose coverage among girls in cohort 2, which may be due to the fact that the first dose was not recorded in some cases and/or improvements in recording for the second dose14-16.
Our findings show that the number of health regions achieving adequate coverage decreased from the first to second dose in both girls and boys. At municipal level, more than half of municipalities achieved adequate first dose coverage among girls in cohort 1; however, second dose coverage, which shows vaccination completeness, was considerably lower than first dose coverage.
In line with our findings, a previous study found that 89 municipalities in Maranhão reached or exceeded the 80% coverage target for girls for the first dose, but only 17 cities reached this level for the second dose. Among boys, only four municipalities achieved the target for the first dose and one for the second dose11. Factors that may explain these findings include lack of permission for vaccination from parents/guardians, the fact that parents tend to take responsibility for immunization during childhood and tend to feel less responsible for vaccination when their children become adolescents. Furthermore, some parents/guardians do not authorize their children to take the HPV vaccine for fear that the vaccine leads to increased sexual risk behavior9-11.
The disparities in vaccination coverage rates across health regions found by this study can be explained by complex interactions between different factors, such as access to health services, adequate infrastructure, health awareness and education, local culture and beliefs, access to information, effective public policies and socio-economic conditions15.
Our findings reveal that the distribution of vaccination coverage across municipalities was uneven. Previous studies11,16 have shown that vulnerabilities, including low socioeconomic status, contribute to heterogeneity and nuances in vaccination coverage. It is worth mentioning that the state of Maranhão is characterized by deep social inequalities17, meaning it is necessary to implement strategies to increase adherence to vaccination campaigns, especially for subsequent doses. Furthermore, it is essential to understand the factors that affect vaccine hesitancy in order to develop policies and health education strategies to address this problem16.
Barriers to increasing HPV vaccination adherence in Maranhão include lack of contact tracing by family health teams, missed opportunities for vaccination, vaccination center opening hours that conflict with parents’ availability and flaws in vaccination recording14.
An important strategy to overcome these barriers is the School Health Program (PSE), which began in 2007 and aims to promote health and prevent vulnerabilities that may affect the development of schoolchildren. Health professionals collaborate to train students, teachers and staff, establishing links that help meet the specific needs of children and adolescents18. During the Covid-19 pandemic, the PSE was severely affected by restrictive measures, resulting in the interruption of face-to-face activities, affecting student access to health services and undermining health education programs. It is also important to stress that the Covid-19 pandemic affected HPV vaccination and coverage globally due to the safety measures implemented around the world19. However, the impacts of the pandemic on HPV vaccination in the state of Maranhão were limited since only female cohorts were eligible for vaccination during the period.
It is expected that Technical Note 41/2024, which recommends single-dose vaccination for boys and girls aged 9-14 and three doses for immunocompromised individuals and victims of sexual violence, will lead to an improvement in vaccination coverage20.
Study limitations include the use of secondary data, which are susceptible to underreporting, and duplication or recording errors. However, the use of spatial analysis techniques has significant potential to support crisis management, as the analysis of the distribution of vaccination coverage shows. In addition, the findings of this study can serve to help identify areas and regions with investment shortages and poor indicators, thus informing decision-making by public managers. The scarcity of previous studies on vaccination coverage across municipalities in Maranhão emphasizes the relevance of this research for understanding and improving vaccination strategies.

Conclusion
Our findings revealed significant gaps in vaccination coverage in Maranhão among both boys and girls. The uneven distribution of vaccination coverage found by this study highlights a number of challenges that need to be addressed to ensure the effective implementation of the vaccination program across municipalities in the state.
The results also reveal the difficulties faced in achieving adequate HPV vaccination coverage in the state\'s health regions and municipalities, reinforcing the need to implement strategies to promote adherence to vaccination campaigns, especially for subsequent doses, and to step up efforts to promote HPV vaccination, especially given the worrying decrease in coverage revealed by this analysis.

Funding
This work was undertaken with support from the National Program for Academic Cooperation in the Amazon (n° 21/2018 – Procad Amazônia – reference number 88881.200531/2018-01).





References
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