SCIFED. Publishers. SciFed Vaccines Research Journal

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1 Research Article SCIFED Publishers Charbell Miguel Haddad Kury,, 2018, 1:1 SciFed Vaccines Research Journal Open Access STD/AIDS Service Genital Warts Incidence Reductions after Quadrivalent HPV Vaccine Introduction in Campos Dos Goytacazes-RJ Municipality *1 Charbell Miguel Haddad Kury, 2 Marcus MHK, 2 Laura WPS, 2 Marcela RF, 2 Andreya Moreira de SSM, 2 Cinthia GL, 2 Hugo OF, 2 Silvia BC, 2 Andrei VVL, 2 Gustavo Siqueira de Castro *1 Camara Junior Street, 42, apt 102 center, municipality of Campos dos Goytacazes, State of Rio de Janeiro, Brazil 2 Universidade Federal do Rio de Janeiro, Campus Macae city, Aloísio da Silva Gomes avenue, 50 - Novo Cavaleiros, ZIP CODE , Brazil, Municipality of Macae, State of Rio de Janeiro, Brazil Abstract There are over 200 different types of human papillomavirus (HPV), but only 30 affect the genital tract. HPV types 6 and 11 are of low risk and cause approximately 90% of genital warts. HPV quadrivalent vaccine is one of the strategies for early prevention of this condition. In September/2010, the municipality of Campos dos Goytacazes were the first one in Brazil that has implemented the quadrivalent HPV vaccination for girls aged between years. In 2011, vaccination was extended for HIV positive women aged 9-26 years. Methods This is a retrospective study who analyzed medical records of teens and women with genital warts treated at Municipal Program of STD/AIDS before and four years after the vaccination started in this city. This study aimed to assess occurrence of genital warts in all patients treated each year for each age group (16-20; 21-25; 26-30; 31-35; 35-40; >40 years old). A survey of vaccination coverage was also performed. Results From , a total of 793 medical records with 247 cases of genital warts (31, 15%) were analyzed. From 2011 to 2014, a total of 817 medical records were analyzed with 244 cases (29, 86%).The most significant reductions in the prevalence of genital warts occurred in and years old. Conclusion Although the studied population was treated in a specific STD program, which caused a tendency to select the candidates, a slight reduction of 1.3% in the prevalence of genital warts was observed, especially in younger vaccinated populations, showing that the vaccination might play an important role in prevention of genital warts. Keywords Sexually Transmitted Diseases; Measures of Disease Occurrence; Genital Warts; Papillomavirus Quadrivalent Vaccine Abbreviations VG: Vaccines Given; PoP: Adolescent Population in the years ; VC: Vaccination Coverage Introduction Human papillomavirus (HPV) is a sexually transmitted infectious agent classified into high and low risk types [1]. There are over 200 types of viruses already * Corresponding author: Charbell Miguel Haddad Kury, Camara Junior Street, 42, apt 102 center, municipality of Campos dos Goytacazes, State of Rio de Janeiro, Brazil. charbellkury@hotmail.com; Tel: Received March 21, 2018; Accepted July 17, 2018; Published July 30, 2018 Citation: Charbell Miguel Haddad Kury (2018) STD/AIDS Service Genital Warts Incidence Reductions after Quadrivalent HPV Vaccine Introduction in Campos Dos Goytacazes-RJ Municipality. 1:1. Copyright: 2018 Charbell Miguel Haddad Kury. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. page 1 of 8

2 Campos Dos Goytacazes-RJ Municipality. 1:1. described [2]. High-risk types, for example, including HPV 16 and 18, are associated with high-grade intraepithelial lesions and invasive carcinomas. While low-risk types such as HPV 6 and 11 are associated with low-grade intraepithelial lesions, they are benign and are related to condylomata acuminate [3]. The average duration of HPV infection is around eight months. After 12 months, 70% of women are no longer infected, and after 24 months, only 9% are still infected, which reveals that the process is transitory. In most cases, the virus is eliminated in a period of two years without medical interventionas it asymptomatic without sequelae [4]. However, persistent HPV infection causes almost all cancers of the cervix and many cancers of the vulva, vagina, penis, anus and oropharynx [5]. Condylomata acuminata, which is one of the most common forms of HPV manifestation, has a small incubation period after viral infection, lasting for about three months. Its incidence is ideal for measuring the effectiveness of the anti-hpv vaccine [6]. Recent studies report that the incidence of genital warts has increased significantly in the period prior to vaccination against HPV. In countries such as Australia, free vaccination was made available for women between 12 and 26 years of age in 2007 [7].The survey carried out by Read et al. in Australia, 2011, reports that disappearance of genital warts in heterosexual men and women under the age of 21 belonging to a population of girls and young women vaccinated 4 years ago should occur in a few years to come. It should be noted that HPV vaccines was not included in the Brazilian National Immunization Program (NIP) until March, Exceptionally, the city of Campos dos Goytacazes, by using its own funds, included the quadrivalent vaccine against HPV in the municipal vaccination calendar on September 13th, 2010, making it available for residents aged years old. Moreover in 2011, using international data, this municipality introduced this vaccine in a specific population; HIV-infected people aged 9-26 years old. This study aims to evaluate the possible reduction in the occurrence of genital warts HPV in Campos dos Goytacazes after the introduction of this vaccination in this population by the investigation of the cases by analyzing the medical records. There was also made a survey of vaccination coverage to access the relationship between the incidence of cases and vaccination coverage. Material and Methods Type of Study The study is observational, historical cohort, retrospective. Features of the City The municipality of Campos dos Goytacazes (Figure 1) is the main city in the interior of the State of Rio de Janeiro, the main national producer of Petroleum, with about 4,032 km² distributed in urban and rural areas with an estimated population of 463,545 inhabitants, of those, 240,000 are women [8]. It is the largest city outside the metropolitan region of Rio de Janeiro, with approximately 276,000 properties (Houses, trade and others) and cut by BR-101 highway, which connects the north to the south of the country. Figure 1: The Municipality of Campos Dos Goytacazes The Municipality was the pioneer in providing 51,000 doses of the quadrivalent vaccine against HPV for a population of 20,000 girls aged 11 to 15 years in the State of Rio de Janeiro in October, Vaccination occurred in all public and private schools. Two fixed health posts were also made available aimed at vaccinating absents, out-ofschool children, or exception cases. The School Health Program conducted educational lectures at all schools receiving the vaccine on HPV. The municipality also began to vaccinate all HIV-positive women from 9 to 26 years of age through the municipal STD / AIDS program [9]. The municipality used its own resources to make the vaccine available and showed that the cost of the vaccine page 2 of 8

3 Campos Dos Goytacazes-RJ Municipality. 1:1. would be less than the cost of treating genital warts and consequently the risk of developing cervical cancer and other HPV-related diseases [10]. Features of the STD (Sexually Transmitted Diseases) / AIDS Program The Program offers services provided by the Center for Infectious and Parasitic Diseases (CDIP), where other services from instances such as the Specialized Attention Service (SAE) and the Center for Testing and Counseling (CTA) are offered. It provides care to patients with general infectious diseases such as toxoplasmosis, and attendance to victims of sexual violence and biological accidents (continuity treatment). It serves the general population (children / adolescents / adults) offering diagnosis of STD / HIV / AIDS and hepatitis B and C. Calculation Method of Vaccination Coverage The calculation of HPV coverage was carried out using the method described by Jose Cassio de Moraes and colleagues (2003) [11], which imputes a ratio between the number of vaccinated and the total number of individuals of the same age group. The female population used in the denominator was calculated for the years 2010, 2011 and 2012, according to the IBGE [12]. They were inserted in the numerator data vaccination for the first and third doses (complete scheme). Description of the Immunobiological The recombinant quadrivalent vaccine against human papillomavirus (types 6, 11, 16 and 18), licensed for pediatric and adult use in Brazil (MSD, 2006), is a sterile preparation for intramuscular administration. Each 0.5 ml dose contains approximately 20mcg of HPV 6 L1 protein; 40mcg of HPV 11 L1 protein, 40 mcg protein of HPV 16 L1 protein and 20 mcg of HPV 18 L1. Its excipients are 225 mcg of aluminum (amorphous aluminum hydroxyphosphate sulfate as an adjuvant); 9.56 mg sodium chloride, 0.78 mg of L-histidine, polysorbate 80 50mcg, 35 mcg of sodium borate and water for injection. The vaccine is given from 9 to 26 years old, in a months of age scheme. Study Population Medical records of women aged 16 years and older, residents in Campos dos Goytacazes who presented with condyloma at the time of medical examination and that are not immunosuppressed, transplanted or pregnant. Collection of Samples The data collection was done with only one consultation to the medical records, and the Term of Free and Informed Consent was exempted of use. The research was carried out with analysis of all medical records of women attended in the Municipal STD/AIDS Program, between 2007 and 2009 (before vaccine implementation) and 2011 to 2014 (after vaccination that started in 2010) in the following age groups: 16 to 20 years, 21 to 25 years, 26 to 30 years, 31 to 35 years, 35 to 40 years and over 40 years, in Campos dos Goytacazes - RJ. Sampling Analysis The study was divided into pre-vaccination period (January 2007 to December 2009) and post-implementation period of the vaccine (January 2011 to December 2014). The incidence of patients diagnosed with genital warts was calculated in perceptual from the number of women diagnosed with genital warts by the total number of women treated in the STD/AIDS program. In addition, data were stratified by age groups of 16 to 20 years, 21 to 25 years, 26 to 30 years, 31 to 35 years, 35 to 40 years and over 40 years. The data were inserted in Epidata system, and the Epidata Analysis was used to report in percentuals the incidence of genital wartsin pre- and post-vaccinal periods. Results From 2007 to 2009, 793 medical records were analyzed, with a total of 247 cases of genital warts, which corresponds to a percentage of 31.15%. The highest incidence was observed in From 227 medical records, 74 cases were diagnosed with condyloma, representing 32.60% cases in this year (Table 1), which corroborates results of Australian studies that indicate an increase in the incidence of condyloma in the pre-vaccine period [7]. It is observed that from a total of 41 cases of condyloma, 30% occurred in women between years old. With the free implementation of the vaccine in the municipality of Campos dos Goytacazes in September 2010, initially 3 doses were administered, respecting the interval of months. The year 2011, as well as the year 2010, was conceived as a transition year, which did not show incidence reduction of condyloma cases; on the contrary, compared with 2009, there was an increase of 3.24% cases. When analyzing the 212 medical records of 2011, 76 of them were diagnosed as condyloma, page 3 of 8

4 Campos Dos Goytacazes-RJ Municipality. 1:1. corresponding to 35.84% of cases. From that year on, the incidence of genital warts gradually decreased: 32.13% in 2012, 27.5% in 2013, and 20.83% in 2014 (Table 2). When comparing incidence of 2009 and 2014, a significant reduction of 11.77% in condyloma incidence was observed (Table 3). When analyzed by age groups, the most significant reduction in prevalence of genital warts occurred in women between 16 and 20 years of age (Graphs 1 and 2): in 2009 incidence was of 41.90% and of % in 2014, showing decrease of 9.64% in cases. The age groups who did not receive the vaccine showed increase in case incidence, the most significant occurred in the age group Table 1: Before Anti HPV Vaccine (2007, 2008, 2009) that ranged from 21 to 25 years, with increase of 6.89%; 31 to 35 years, with increase of 5.63%; and over 40 years, with increase of 8.85%. In Table 4 is disclosed the cumulative coverage for each age, considering the years , showing the methods used to calculate coverage, and distributed by each age in each year of interest. *In 2010 there was not given the 3rd dose in any teen, because the implementation of the quadrivalent vaccine started in September, In 2014 the HPV vaccination schedule changed for a two doses scheme only for girls aged years old Age 2007 % 2008 % 2009 % Total % y % % % % y % % % % y % % % % y % % % % y % % % % > 40 y % % % % Total condyloma % % % % total medical records % Table 2: After Anti HPV Vaccine (2011, 2012, 2013, 2014) Age (years) 2011 % 2012 % 2013 % 2014 % Total % years % % % % % years % % % % % years % % % % % years % % % % % years % % % % % > 40 years % % % % % Total condyloma % % % % % total medical records % Table 3: Comparison of Pre and Post Vaccination Age (years) Percentage of cases in 2009 Percentage of cases in years 41.90% 32.26% years 18.92% 25.81% years 13.51% 3.26% years 4.05% 9.68% years 5.41% 6.45% > 40 years 4.05% 12.90% Total condyloma* 32.60% 20.83% * Regarding the general medical records analyzed page 4 of 8

5 Campos Dos Goytacazes-RJ Municipality. 1:1. Graph 1: Occurrence of Genital Warts in Campos dos Goytacazes Graph 2: Occurrence of Genital Warts in Campos dos Goytacazes page 5 of 8

6 Campos Dos Goytacazes-RJ Municipality. 1:1. Table 4: Quadrivalent HPV Vaccine Coverage among Adolescents By Dose And Year Of Vaccination, Campos Dos Goytacazes, Brazil years 13 years 14 years 15 years 1st dose 1583/4083 = 38.7% 1695/3923=43.2% 2321/3969=58.4% 1930/4031=47.8% 3219/4280=75.2% 52.90% 3st dose* years 13 years 14 years 15 years 1st dose 3756/4122 = 91.1% 3121/3960=78.8% 3948/4007=98.5% 3210/4069=78.8% 4231/4321=97.9% 89.02% 3st dose 2650/4122 = 64.2% 2054/3960=51.8% 3218/4007=80.3% 2430/4069=59.7% 2980/4321=68.9% 65.10% years 13 years 14 years 15 years 1st dose 3680/4159 = 88.4% 3054/3996=76.4% 3890/4042=96.2% 3460/4105=84.2% 4087/4359=93.7% 87.90% 3st dose 2423/4159 = 58.2% 3112/3996=77.8% 2980/4042=73.70% 2646/4105=64.4% 2530/4359=58% 66.20% years 13 years 14 years 15 years 1st dose 3998/ 4250= 94% 4201/4059=103% 3200/4134=77.4% 2478/4230=58.5% 2356/4489=52.4% 77.00% 3st dose 1982/4250 = 46.6% 1568/4059=38.6% 1365/4134=33% 1785/4230=42.1% 1465/4489=32.6% 38.00% years 13 years 1st dose 4550/4320= 105% 5215/4220=123% 4165/4321=96.3% % 2st dose 4128/4320= 95.5% 4687/4220=110% 3998/4321=92.5% 99.30% Discussion and Conclusion HPV is considered a sexually transmitted disease and HPV infection is associated with occurrence of the most varied types of disease outcomes, from benign associations such as condyloma, to other malignant morbid forms such as cancer of the uterus and the anus. Prevention of all these conditions occurs with use of the condom, but more effectively with quadrivalent vaccine administration [13, 14]. The present study demonstrates how the vaccine is one of the actions that are of greatest impact on society in public health. However, phobia of injection, access to social networks and dissemination of information, sometimes erroneous or false, amplifies resistance to vaccinate. Therefore, it is necessary to have clear, accessible scientific information to demonstrate society of the importance of this and other vaccines [15]. This study showed that the use of the quadrivalent HPV vaccine reduced the incidence of genital warts in 11.77% from 2009 to 2014, specifically in younger populations, to which the vaccine was available. Part of these patients was given the vaccine at school, probably before they became sexually active. In the age groups that did not receive the vaccine, there was a significant increase in the incidence of cases. Similar results were reported in recent studies carried out in Australia, one of the first countries that made the vaccine available throughout its territory for free. In 2007, vaccination was offered in schools for girls between 12 and 13 years of age; from 2007 to 2009, other programs carried out in schools covered girls between the ages of 13 and 18 years old and another program, carried out in the community covered women between the ages of 18 and 26 years. Two years after starting of vaccination, the page 6 of 8

7 Campos Dos Goytacazes-RJ Municipality. 1:1. incidence of genital warts was reduced by 59% in women between 12 and 26 years old, representing the population for which the vaccine was made available [16-18]. Sweden also published a study demonstrating a significant decline in incidence of genital warts in girls and women vaccinated before the age of 20. The effectiveness of the vaccine was of 76% for those who received the three doses, the first before the age of 20 years. The maximum effectiveness of the vaccine, around 93%, occurred among girls vaccinated before the age of 14 [6]. Other coutries like Israel and Belgium are also showing this tendency in reduction of the genital warts [19, 20]. This study presents several limitations. The first did not know the following information, since they were not registered in the medical records: from the group of girls entitled to receive the vaccine, how many were actually vaccinated. And also, from the vaccinated group, how many doses they received. The second limitation is related to the population treated in a specific STD program, where practically all patients diagnosed with genital warts in the municipality (except private health care) are referred for both treatment and follow-up. This procedure may lead to a tendency for patient selection. The third limitation refers to the temporal nature of the condylomatous disease, which may regress regardless of the use of the vaccine, thanks to the individual s immune system, and therefore the observed reduction may have occurred at random. However, despite biases, a significant reduction in the incidence of condylomata was observed, confirming that the only possible intervention in that specific group in the period of time treated in this study was the vaccine at the time of its introduction, showing its unequivocal possibility of protection. We conclude that the use of the quadrivalent prophylactic vaccine against HPV was an adequate public health strategy in populations that attended the specific STD treatment programs. This was demonstrated by reduction in the prevalence of condylomatous lesions after mass vaccination of girls in this municipality. It should be noted that in 2014 the Brazilian Minister of Health started HPV vaccination for girls, which led the municipality exclusively to extend vaccination for boys aged years. So, there might be a possibility for a more intense reduction in genital warts after all. References 1. Girianelli VR, Thuler LCS, Silva GA (2010) Prevalence of HPV in women assisted by the Family Health Strategy in the Fluminense Bay of Rio de Janeiro State. Braz Ginecol Obstet 32: Nakarawa JTT, Schirmer J, Barbieri M (2010) HPV and Uterine Cervical Cancer Virus. Braz J Nurs 63: Carvalho MOO, Carestiato FN, Perdigão PH, et al. (2005) Human Papillomavirus Infection in Rio de Janeiro, Brazil: a Retrospective Study. Braz J Infect Dis 9: Giraldo PC, Silva MJPMA, Fedrizzi, et al. (2008) Prevention of HPV infecton and lessions assoaciated with the us e of vaccines- Review Article. Braz J Sex Transm Dis 20: Afonso LA, et al. (2013) Human papillomavirus infection among sexual partners attending a Sexually Trasmitted Disease Clinic in Rio de Janeiro, Brazil. Braz J Med Biol Res 46: Leval A, Herweijer E, Ploner A, et al. (2013) Quadrivalent Human Papillomavirus vaccine Effectiveness: A Swedish National Cohort Study. J Nat l Cancer 105: Baandrup L, Blomberg M, Dehlendorff C, et al. (2013) Significant Decrease in the Incidence of Genital Warts in Young Danish Women After Implementation of a National Human Papillomavirus Vaccination Program. Sex Transm Dis, Denmark, 40: Demographic Census (2010) Ministry of Planning, budget and management. Brazilian Institute of Geography and Statistics -IBGE. Brazil. 9. Venancio GAP, Kury CMH (2012) Letter to the Editor. DST- Braz J Sex Transm Dis 24: Kury CMH, Kury MMH, Silva RMH, et al. (2013) Implementation of the quadrivalent vaccine against HPV in the Municipality of Campos dos Goytacazes, Brazil- A combination of strategies to increase immunization coverage and early reduction of genital warts. Trials in vaccinology 2: Moraes JC, Ribeiro MCS, Simoes O, et al. (2003) What s the real vaccination coverage? Epidemiol Serv Saude 12: Merck Sharp, Dohme (MSD ) (2011) Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant Vaccine. Internationally known as Gardasil. Product Monograph Villa, Prophylatic L (2006) HPV vaccines: reducing the burden of HPV-related diseases. Vaccine 24: Ayres ARG, Silva GA (2010) Prevalence of HPV infection page 7 of 8

8 Campos Dos Goytacazes-RJ Municipality. 1:1. in the uterine cervix in Brazil: a systematic review. Rev Saude Publica 44: Roitman B. (2015) HPV: a new vaccine in the public network, Bol Cient pediatric 04: ALI H, Donovan B, Wand H (2013) Genital warts in Young Australians Five years into national human papillomavirus vaccination programme: national surveillance data.bmj, 346: Brotherton JML, et al. (2011) Early Effect of the HPV Vaccination Program on Cervical Abnormalities in Victoria, Australia: an Ecological Study. The Lancet, Austrália 377: Donovan B, Read TR, Hocking JS, et al. (2011) The near disappearance of genital warts in young women 4 years after commencing a national Human papillomavirus (HPV) vaccination programme. Sex Transm Infect 87: Lurie S, Mizrachi Y, Chodick G (2017) Impact of quadrivalent human papillomavirus vaccine on genital warts in an opportunistic vaccination structure. Gynecol Oncol 146: Dominiak-Felden G, Globbo C, Simondon F (2015) Evaluating the Early Benefit of Quadrivalent HPV Vaccine on Genital Warts in Belgium: A Cohort Study. PLoS One 10: e Citation: Charbell Miguel Haddad Kury (2018) STD/AIDS Service Genital Warts Incidence Reductions after Quadrivalent HPV Vaccine Introduction in Campos Dos Goytacazes-RJ Municipality. SF Vacc Res J 1:1. page 8 of 8