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Environmental factors associated with human papillomavirus vaccine coverage in adolescents: 2016-2020 analysis

Abstract Objective: to analyze the association between the factors of the social environment and the coverage rates of the human papillomavirus (HPV) vaccine in adolescents, in the State of Minas Gerais, Brazil. Method: this is an epidemiological, ecological study, with panel and trend analysis from 2016 to 2020. The population consisted of adolescents aged 9 to 13 years. The environmental variables were coverage rates, the municipal index of human development, income, education, and longevity; and the rate of violence. The Prais-Winsten autoregression and the panel regression model were used, in addition to the estimate of the mean annual percentage variation. Results: the vaccination coverage rates are below the goals recommended by the Ministry of Health for all regions analyzed. Moreover, these rates are associated with factors related to the application of the first dose and to aspects inherent to the social environment, such as the rate of violence. Conclusion: our findings showed that, although tenuous, aspects of the environment, in addition to individual characteristics, provide relevant information to understand the occurrence of health outcomes, since this vaccination campaign presents a strong influence of the environment and age as factors associated with the low rates.


Introduction
The human papillomavirus (HPV) is one of the most prevalent sexually transmitted infections in the world (1) .
HPV is a virus capable of infecting the skin and mucous membranes of humans and, depending on its subtype and the persistence of the infection, is associated with the appearance of anogenital and cutaneous warts and neoplasms of the anogenital tract, the most frequent being cervical cancer (1)(2) .
Cervical cancer is a preventable, curable disease with high morbidity and mortality worldwide. In Brazil, this type of cancer ranks third among malignant neoplasms in women and fourth in mortality (2) . The main strategy to control this neoplasm is primary prevention using the HPV vaccine (1) .
The HPV vaccine was introduced worldwide more than ten years ago, but many countries still find barriers to maintain vaccination coverage rates at recommended levels (1,3) . In Brazil, the goal estimated by the Ministry of Health (MS), for each dose, is 80% (4)(5) . Previous studies prove that the goal recommended by the MS covers a large part of the target population, adolescents, since this vaccine should preferably be administered before the beginning of sexual life due to the natural history of the disease. Moreover, this goal aims to achieve collective protection against HPV, thus avoiding cervical cancer (1,(3)(4)(5)(6) .
In 2020, the World Health Organization (WHO) launched a global strategy for the elimination of cancer, establishing the increase of goals by the year 2030 (3) .
One of these goals is for countries to reach a 90% HPV vaccination rate for all target audiences, i.e., girls and boys aged 9 to 15 years (3) .
In Brazil, the implementation of the HPV vaccine in the calendar of the National Immunization Program (PNI) occurred in 2014 and, since then, a vaccination routine has been gradually established (4)(5) . Currently, this vaccine is offered to both female and male adolescents, in the age groups 9 to 13 years and 11 to 14 years, respectively, in a two-dose regiment, with a six-month interval in between (4) . To achieve fully effective immunity, the vaccine must be applied in its complete regimen, that is, in two doses, according to the age group and the established criteria (4)(5) .
Regarding HPV vaccine coverage rates in Brazil, they are not considerably different from vaccine coverage in other countries but are insufficient to achieve the global goal for the eradication of cervical cancer (3,(6)(7) .
In 2014, soon after its implementation, 87% of Brazilian municipalities reached the goal recommended with the first dose, but only 32% of them reached the goal recommended with the second dose (6) . Currently, the coverage rates of the second dose are increasingly lower throughout the Brazilian territory.
The analyses on the vaccination strategy of the first and second dose of this vaccine show that the first was performed on a large scale and with great coverage by the media, being widely disseminated and offered in municipal and state schools (6)(7)(8) . This aspect may justify the above average rates recommended in almost the entire national territory. Regarding the second dose and subsequent years, however, the HPV vaccine started to be offered only in health centers, which may be one of the reasons for the low rates of vaccination coverage (6)(7)(8) .
The search for increased vaccination rates for adolescents creates many challenges. Among which, we highlight the decision to vaccinate, either made by those responsible for the adolescents or by the adolescents' themselves. Regarding the rejection of this vaccine, it occurs mostly due to the spread of fake news (8) .
Overall, the acceptability of vaccines is a complex process that can be affected by several factors. Regarding the decision to vaccinate, in 2014, the Strategic Advisory Group of Experts (SAGE) sought to understand the determinant factors of vaccination (9) .
The group developed a model organized in three main areas: (1) contextual influences: historical, sociocultural, environmental, health system/institutional, economic or political factors; (2) individual and group influences: arising from the personal perception of the vaccine or influences of the social environment; and (3) specific vaccines issues: which are those directly related to the characteristics of the vaccine or the process of vaccination (9) . The term "vaccination hesitation" was defined as the delay in accepting or the rejection to the vaccine, despite its availability (9) .
Other contributing factors are added to the adolescents' low access to vaccines, such as: social and economic vulnerability and issues related to the difficulties for this public to access health services, often because they do not seek care and, when they seek it, they find little guidance (few of which are correct) from health professionals (1,8,(10)(11)(12) . Thus, we can observe the significant role the nursing professional plays in this scenario. In Brazil, this professional is mostly responsible for the management of primary health care services and is at the forefront of vaccination campaigns, playing an extremely politically relevant role in gaining a better adhesion of adolescents, besides being a reference for the health team (7)(8)(10)(11)(12) .

Study design
This is an epidemiological, ecological study, in which panel and trend analysis were carried out.

Location
The study was conducted in the state of Minas Gerais, Brazil.

Period
The study was conducted from 2016 to 2020.

Study population
The study population consisted of female and male adolescents, aged 9 to 13 years, who were vaccinated against HPV.
The period and age group framing of this study is justified since it focuses the target audience of the vaccine in question and encompasses the completeness/ consolidation of the online system data from 2016.
The municipalities are delimited from cultural, economic, and social identities and shared transport networks and networks, with the purpose of integrating the organization and planning of health actions and services (14) .

Study variables
All data from this study were extracted through secondary databases, available on government websites.
The HPV vaccine data were extracted from the Information System of the National Immunization Program

Data processing and analysis
In the formula, Y represents the dependent variable, β represents the variation observed in Y when the independent variable, X, increases in one unit and ε indicates the stochastic nature of the model. Finally, the Hausman test was performed to verify the consistency of the model.

Ethical aspects
Since this study used free access data, the project was not required to be submitted to the Research Ethics Committee, according to resolution 466/2012 of the National Health Council (17) .  Table 1 shows HPV vaccine coverage rates by age group, year, and trend. We observed that the variations in coverage rates had a higher proportion in the 9-year-old age group, and in 2017 the highest rate occurred for D1.

Results
On the other hand, the lowest rate occurred for the older ages, with the 13-year-old age group being the one that stood out the most from the other groups. Regarding trend analyses, we found that only the 9-year-old age group was increasing, and all other age groups were decreasing.      was the year in which the HPV vaccine was introduced for the male adolescent population in Brazil. However, these rates did not reach the expected increasing values, nor the ones obtained in other countries (18) .
Australia, a pioneer country in the introduction of HPV vaccine in its national vaccination program for both girls and boys, currently has good results in reducing the incidence of cervical cancer thanks to the vaccination coverage rate, which ranges from 70% to 80% throughout its territory (18)(19) .
Brazil was the first country in South America and the seventh in the world to offer the HPV vaccine to boys in national immunization programs. The availability of immunobiological strains for boys also provides crossprotection for girls, in addition to protecting against cancers in the penis, throat, and anus, all diseases that are directly related to HPV (1,5,18) . However, for this to happen, the coverage rates for this public must be within the established goals (5-6, 18) .
Another finding of this study refers to the fact that Studies show that the COVID-19 pandemic had a significant influence on public health and that HPV vaccine coverage was also affected (20) . However, this reality is not exclusive to this vaccine, but it is one shared with other regular vaccines (20)(21)(22)(23) .
In the comparison between the cohorts, the presenting an increasing trend. This is an extremely relevant factor within the context of HPV vaccination; the population in this age group is the one that benefits most from this immunobiological, since people have not yet been exposed to the viral subtypes of HPVwhich makes the vaccine have a greater power of efficacy and immunogenicity against the subtypes of the applied vaccine (8,18,23) .
This targeted age group of the HPV vaccine is an important and relevant factor for public health, since historically most immunization programs have focused on childhood vaccination. Thu, health services may be less experienced in reaching and vaccinating adolescents (3,(7)(8) . This fact can be proven by the low rates of vaccination coverage found in this study, as well as in other countries, since many have limited experience in providing and continuing health care to adolescents, in addition to beliefs/barriers imposed in the context of this immunobiological (6)(7)(8)10) .
In this study, we also found similarity in vaccination coverage rates among the regions of Minas Gerais (SRS/ GRS), which may be associated with regional and even state-level public policies.
To improve HPV vaccine coverage rates, low-and middle-income countries, such as India, Peru, Uganda, and Vietnam, have adopted vaccination strategies within community and schools. They emphasize that, to increase the acceptability of this vaccine, other interventions are needed, such as sex education, knowledge, and good health practices. Many of these actions are performed by the nursing professionals (8,(18)(19)(22)(23) .
Regarding the characteristics of the social environment, the analysis presented here suggests an association between low vaccination coverage and high crime rates by region. Studies show that regions with higher value of this indicator can represent both more rural areas and urban areas of low economic level, which causes strong consequences for economic, social, and health development (23)(24)(25) .
Geographical barriers can also influence the reduction of access to vaccination services (24) . The SAGE group related, for example, geographical barriers to the hesitation to vaccinate. This occurred when the population was motivated to receive a vaccine but hesitated due to the fact that the health center was distant, or its access was hindered (9) -this difficulty may be imposed by the insecurity of going to the health service (24) due to the rates of violence in each region.
Thus, crime can directly interfere in the performance of health care by limiting access to services, causing the population not to attend the health unit (25)(26)(27) . Again, we emphasize that, to our knowledge, there are few national studies that address the impact of crime index, especially on the health of adolescents.
Territorial characteristics, such as regional inequalities and the peculiar characteristics of each state/ region (public security policies, economic infrastructure, health, education, and demographic structure), are extremely important factors for the development of public health strategies (18)(19)23) . When developing strategies to raise awareness of the importance of HPV vaccination, it is necessary to adapt them according to the socioeconomic and socio-environmental characteristics of the location. In this case, the nursing professional is able to contribute to this process through situational analysis of the population and with the use of tools, such as situational diagnosis (7,27) .

Conclusion
The evidence found in this study may contribute to improve the understanding of the complex relationship between environmental and individual determinants and vaccination, which may play an important role in expanding public health strategies and policies. We aim to contribute to the increase in vaccination coverage rates in adolescent public not only within the State of Minas Gerais but also within the entire country.