J I a G E a A b U R J h 1 ournal of Infection and Public Health (2015) 8, 105—116 ndications for the HPV vaccine in dolescents: A review of the literature láucia Resende Soaresa, Rúbia da Rocha Vieiraa, duardo Piza Pellizzerb, Glauco Issamu Miyaharaa,∗ Oral Oncology Center, Department of Pathology and Clinical Propaedeutics, raçatuba School of Dentistry, UNESP — Univ Estadual Paulista, Araçatuba, SP, Brazil Department of Dental Materials and Prosthodontics, Araçatuba School of Dentistry, NESP — Univ Estadual Paulista, Araçatuba, SP, Brazil eceived 17 March 2014; received in revised form 13 June 2014; accepted 24 August 2014 KEYWORDS Vaccine; HPV; Adolescent Summary Background: The vaccine against human papillomavirus (HPV) was created to abro- gate the risk that the virus presents for the development of cervical cancers. The prevalence of HPV infection among healthy individuals is significant (20%). We per- formed a review of the literature published in the period from 2008 to 2012 regarding the use of the vaccine against HPV specifically in adolescents. Methods: The articles were selected from a search of the PubMed database with the key words ‘‘vaccine’’, ‘‘HPV’’ and ‘‘adolescent’’. This search identified 576 articles; based on readings of the titles and abstracts, the list of included article was reduced to 42. Results: We observed that the majority of authors are in favor of the vaccine for adolescents particularly females. Conclusion: Recommending the use of the HPV vaccine and other vaccines repre- sents an attempt to broaden the reach of these vaccines among both sexes of the adolescent population. Vaccination is a strategy for the prevention of pre-cancerous lesions in the genital and oropharyngeal regions. © 2014 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Limited. All rights reserved. ∗ Corresponding author at: Centro de Oncologia Bucal, Faculdade de osé Bonifácio, 1193, CEP 16015-050 Araçatuba, SP, Brazil. Tel.: +55 E-mail address: miyahara@foa.unesp.br (G.I. Miyahara). ttp://dx.doi.org/10.1016/j.jiph.2014.08.011 876-0341/© 2014 King Saud Bin Abdulaziz University for Health Scie Odontologia de Araçatuba, Universidade Estadual Paulista, Rua 18 36363275; fax: +55 18 36363332. nces. Published by Elsevier Limited. All rights reserved. dx.doi.org/10.1016/j.jiph.2014.08.011 http://crossmark.crossref.org/dialog/?doi=10.1016/j.jiph.2014.08.011&domain=pdf mailto:miyahara@foa.unesp.br dx.doi.org/10.1016/j.jiph.2014.08.011 106 G.R. Soares et al. Contents Introduction ................................................................................................ 106 Methods..................................................................................................... 106 Search strategy......................................................................................... 106 Study selection......................................................................................... 106 Inclusion/exclusion criteria............................................................................. 107 Outcomes and variables ................................................................................ 107 Results...................................................................................................... 107 Study sample........................................................................................... 107 Recommendations of physicians regarding HPV vaccination............................................. 107 Recommendation regarding HPV vaccination for females and males .................................... 107 Availability of the vaccine to society ................................................................... 113 Discussion................................................................................................... 113 Conclusion .................................................................................................. 115 Funding ..................................................................................................... 115 Competing interests ........................................................................................ 115 Ethical approval ............................................................................................ 115 References.................................................................................................. 115 Introduction World estimates have indicated that 20% of healthy individuals are contaminated with the human papillomavirus (HPV) and that this virus is primar- ily transmitted through sexual contact, although direct contact with contaminated objects can also lead to infection. HPV is related to the development of approximately 98% of the cases of cervical can- cers; thus, infection with the virus is a public health problem, and the prevention of such infections is mandatory [1—4]. The prophylactic vaccine against the HPV L1 viral particle is an effective method for the prevention of the infection of naïve women and HPV-negative persons; therefore, the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention have recommended the universal administration of the three doses of quadrivalent or bivalent HPV vaccine to girls of 11—12 years of age, although the minimum recom- mended age varies with geographic region [2,5,6]. Based on a cost—benefit analysis, the ACIP rec- ommended the administration of the anti-HPV virus to 11- or 12-year-old girls for the prevention of gen- ital warts, anal cancer and possibly cancers of the head and neck because the vaccine is considered to be highly effective and provides protection against the four types of HPV [7,8]. Parents’ interest vaccinating their children and the interest of adults (up to 26 years of age) in get- associations between some types of cancer and HPV [4,9]. To increase the knowledge of the use of the prophylactic HPV vaccine in adolescents, we per- formed a review of the published literature that broadly discussed this subject in the period from January 2008 to August 2012. Methods Search strategy The PubMed database was searched for relevant articles published in English from 2008 to August 2012. The studies were grouped according to whether they evaluated the indications for adminis- tration of the HPV vaccine to adolescents. A broad search strategy was pursued to capture the rele- vant studies of the HPV vaccine and the indications for the HPV vaccine in adolescents. The keywords ‘HPV’, ‘vaccine’ and ‘adolescent’ were used. Data from longitudinal studies were included, and the references of the retrieved articles were analyzed to identify additional relevant studies. Study selection The studies were selected based on their titles and abstracts, and articles without available abstracts ting vaccinated are directly related to the relevant party’s knowledge of the efficacy of the vaccine, and studies have demonstrated that the acceptance of the vaccine is greater people are aware of the a t c o nd full-texts were excluded. Agreement between he readers was determined statistically, and any onflicts were resolved by discussion or the analysis f a third reader (GIM). This procedure was applied I 107 a e I T t c a a e i v e o n o t H s v t s s m g c n a d O T i t i r a R S T c a f ( o Table 1 Exclusion criteria applied to articles obtained from the search of PubMed for articles pub- lished in the period from January of 2008 to August of 2012. Exclusion — subject or language Number of articles Acceptance, awareness and applicability 269 Effectiveness 56 Cost × benefit of the vaccine 39 Barriers to implementation of the vaccine 27 Impact of the vaccine 26 Estimate of population immunized 26 General concepts about the vaccine 17 Opinion of persons vaccinated 15 Perspectives of the vaccine in prevention 13 Most frequent types of HPV 11 Use of the 3 doses (clinical routine) 7 Simultaneous use of vaccines 6 Other languages 5 Ethical and legal questions 4 Vaccination strategies 3 Sexual behavior after vaccination 3 Perspectives for the control of cancer 2 Men’s intention of getting themselves vaccinated 2 Expression of genes and production of antibodies 2 Free-of-charge vaccine distribution by clinics 1 R H O m H c u n o s t c R f T ndications for the HPV vaccine in adolescents t all selection stages. The full-text articles were valuated by the readers using a pilot-test form. nclusion/exclusion criteria he inclusion criteria were the following: indica- ions for the administration of the HPV vaccine to hildren and adolescents regardless of age group nd sex, and scientific research projects. Simple nd systematic reviews were also included. Studies with the following main themes were xcluded: acceptance, awareness and applicabil- ty of the prophylactic HPV vaccine; efficacy of the accine; costs and benefits of the vaccine; barri- rs to the implementation of the vaccine; effect f the vaccine on society; estimates of the immu- ized population; general concepts of the vaccine; pinions of vaccinated persons; perspectives on he vaccine in prevention; most frequent types of PV; use of the three doses in clinical routines; imultaneous use of vaccines, including the HPV accines; other languages; ethical and legal ques- ions regarding the use of the vaccine; vaccination trategies; sexual behavior after vaccination; per- pectives for the control of cancer; intentions of en to have themselves vaccinated; expression of enes and productions of antibodies; and free-of- harge distribution of vaccines by clinics. When ecessary, the exclusion criteria were reviewed, nd the abstracts were re-assessed until a complete efinition of the exclusion criteria was determined. utcomes and variables he following information was extracted from each ncluded study: year of publication; age-range of hose for whom the vaccine was indicated; sex ndicated to receive the vaccine; recommendations egarding HPV vaccination of physicians; and the vailability of the vaccine to society. esults tudy sample he search detailed above resulted in the identifi- ation of 576 articles. After reading the titles and bstracts, 534 articles were excluded because they ocused on other subjects related to the vaccine Table 1). Thus, our review encompassed a total of nly 42 articles. p p t a Total 534 ecommendations of physicians regarding PV vaccination f the 42 included articles, five addressed recom- endations regarding the prophylactic use of the PV vaccine (bivalent or quadrivalent) by physi- ians (Table 2). Most of the physicians favored the se of the vaccine. However, many clinical opportu- ities were lost. Possible reasons for these missed pportunities included the short time of each con- ultation, forgetfulness on the part of doctor, and he population’s absence of interest in the HPV vac- ine due to lack of information. ecommendation regarding HPV vaccination or females and males he 42 included articles were in favor of the pro- hylactic use of the HPV vaccine; these articles articularly emphasized the potential benefits for he prevention of cervical cancers. The percent- ges of articles that recommended the use of the 108 G .R. Soares et al. Table 2 Recommendations regarding the prophylactic use of the HPV vaccine of each relevant article. Author and year of publication Sex Indication for Main comments Nadal and Nadal (2008) [3] Female 11—25 years Vaccination does not dispense with the need for period exams to trace anogenital cancers, and for the present moment it is indicated for women from 11 to 25 years of age, and is not indicated for men.Male Non-indicated Somasundaram (2008) [5] Female 9—26 years or more young HPV infections occur within a few years of the beginning of sexual activity, thus it is believed that the prophylactic HPV vaccine should be administered before 9 years of age in India. However, it is necessary for studies to be conducted about the efficacy of the vaccine at this age.Male — Mammas et al. (2009) [6] Female 9—26 years Understanding the natural history of HPV infection will allow the application of prophylactic HPV vaccines in the most correct age groups for the prevention of Uterine cervix carcinoma (UCC), however, it is agreed that the vaccine is beneficial to the female sex (9—26 years).Male — Wright et al. (2009) [11] Female 11—26 years and older women In addition to the benefits of the vaccine to girls from 11 to 26 years, vaccination can also benefit females over the age of 26 years who have not been previously exposed to HPV 6, 11, 16, or 18 and those who may have new sexual partners in the future.Male — Garland et al. (2011) [12] Female 12—13 years Discusses the benefits of the vaccination program in girls (12—13 years) at schools in Australia, showing that within a short time after implementation, a reduction was observed in genital warts diagnosed in STD clinics.Male — Etter et al. (2012) [13] Female 9—26 years Although the quadrivalent prophylactic HPV vaccine has been approved since 2006, and the bivalent vaccine since 2009, the rates of uptake and completion of the series of doses among young women continue to be low.Male — Kahn et al. (2009) [15] Female 9—26 years, Priority: 11—12 years The study informs that doctors are increasingly more inclined to indicate prophylactic HPV vaccine for the male sex as well, but there is still the need for specific information with respect to the vaccine for the male sex. Male Priority: 11—12 years Vadaparampil et al. (2011) [16] Female 11—26 years The study suggests that innumerable clinical opportunities for the application of HPV vaccination are lost, particularly within the first years of adolescence in the female sex (11—12 years). Male Suggest 9—26 years Weiss et al. (2010) [17] Female 13—26 years Doctors who support the use of prophylactic HPV vaccine for the female sex also believe in the benefits of the use of the vaccine for the male sex. However, they do not agree that adoption of the vaccine for both sexes would favor vaccination coverage, or even change the opinion of adolescents’ parents with regard to the importance of the vaccine.Male 13—26 years Krupp et al. (2010) [18] Female 9—26 years The article evaluates the indication of prophylactic HPV vaccine by doctors in India, and observes that the minority indicate this with the justification that there is no time during the consultation to explain the benefits of the vaccine, since they perform 40 attendances per day, which allows less than ten minutes per consultation.Male — Indications for the H PV vaccine in adolescents 109 Akinsanya-beysolow and Wolfe (2009) [19] Female 9—26 years Reinforces the need for all gynecologists to explain the benefits and safety of prophylactic HPV vaccine to the women who consult them, because in addition to being benefited by this information, they may take their children (present or future) to receive the vaccine, thus increasing this vaccination coverage. Male Licensure of HPV vaccine has been applied for Moscicki (2008) [20] Female 9—26 years Emphasizes the need for creating vaccines for women who have begun sexual activity, since the existent prophylactic vaccines are destined and efficient for women who have not yet engaged in sexual activity.Male — Frazer (2008) [21] Female Until 25 years Understands that the prophylactic HPV vaccine is a strong weapon for the prevention of uterine cancer and other lesions associated with HPV. It has been used in many countries in women up to 25 years of age, who have not engaged in sexual activity, an in men based on the safety and immunogenicity of the vaccine. Male Suggest until 25 years too Castle et al. (2009) [22] Female Until 26 years Examining data from 7 clinical centers in the USA, the median age of CIN2/3 is typically between 25 and 30 years of age in 2007; if screen-detected CIN2/3 develops on average 5—10 years after the causal infection is acquired, HPV vaccination will only prevent a significant proportion of CIN2/3 if it is given to women before the age of 26 and more so if given to women 18 and younger.Male — Westra et al. (2011) [23] Female 12—16 years, but can be used until age 25 Based on cost—benefit, it is believed that the preventive vaccination program should consider the target population of the female sex up to 25 years of age. After this age, the preventive program should be of another type, composed of routine exams.Male — Harper and Paavonen (2008) [24] Female Priority: until age 25, but indicate for older women Inform that the safety and efficacy of prophylactic HPV vaccine are maintained when used in older women (over 55 years) who do not present viral DNA; Therefore they confirm that women over the age of 26 years need to be informed about this opportunity of being immunized.Male 9—15 years Kim et al. (2010) [25] Female 10—14 years Evaluates the safety and efficacy of prophylactic HPV vaccine (CervarixTM, GlaxoSmithKline Biologicals, Rixensart, Belgium) with adjuvant AS04 in Korean girls (10—14 years), which was shown to be highly immunogenic and tolerable.Male — Bayas et al. (2008) [26] Female 8—14 years The optimal vaccination strategy is vaccination of girls aged 8—14 years. Other strategies should include the uptake of adolescent and women not yet sexually-active, as well as the vaccination of sexually-active women. The long-term HPV eradication strategy will require universal vaccination of females and males. Male Suggest the vaccine, but not for specific age Reiter et al. (2011) [27] Female Priority: 11—12 years Research conducted in the USA to verify the number of girls (11—12 years) who received prophylactic HPV vaccine, disclosed that few girls were immunized. The immunization strategy proposed is to carry out annual visits for preventive care and administration of vaccines jointly in this age group. Male — 110 G .R. Soares et al. Table 2 (Continued) Author and year of publication Sex Indication for Main comments Palefsky (2010) [28] Female 9—26 years; Priority: 11—12 years In spite of ACIP recommending the use of the vaccine for the male sex since 2009, this recommendation is permissive only and not routinely implemented. Taking into consideration the few means of anal cancer prevention, prophylactic HPV vaccine for men is the best long term approach to prevention of the disease. Male 9—26 years; Priority: 11—12 years Borsatto et al. (2011) [29] Female 9—26 years In a review of articles, informs that the target population for prophylactic HPV vaccination are girls from 9 to 26 years, preferably before they become sexually active.Male — Heideman et al. (2008) [30] Female 9—18 years By means of a review of articles, inform that the vaccine could be administered to girls of prepurbertal age (9—14 years, beginning of sexual libido), girls from 15—18 years, who lost the previous opportunity of being vaccinated, girls over the age of 18 years, who opted for the vaccine and for adolescents of the male sex (10—15 years).Male 10—15 years Mayer et al. (2012) [31] Female Older age 26 Affirms that prophylactic HPV vaccine could be safely administered in older women, a group that is not chosen by public immunization policies, nevertheless, being a group that may also benefit from the use of the vaccine.Male — Committee on Infectious Diseases (2012) [32] Female 9—26 years Provides a detailed approach to fourteen items about recommendations for the vaccine. The article succinctly recommends the vaccine for both sexes (9—16 years), irrespective of whether or not sexual activity has begun. It also recommends it for men over the age of 26 years, who maintain relationships with other men; and for those with HIV. It does not indicate the vaccine for pregnant women and affirms that use of the vaccine does not dispense with the use of condoms and undergoing preventive exams, such as the Papanicolau test (Pap smear).Male 9—26 years Panatto et al. (2009) [33] Female 12—14—16 years They suggest vaccination at three ages (12—14—16 years) as a strategy so that in a short period of time (3—4 years) the group of women from 12 to 20 years could be immunized. The initial cost would be compensated by the savings generated through the reduction in lesions related to HPV.Male — Rama et al. (2010) [34] Female Young primiparous women It was observed that young mothers (15—24 years) presented high prevalence of HPV in the cervical region. However, only 13% of this group of women contained the high risk virus, characterizing a group eligible for receiving the vaccine. Male — Torné et al. (2008) [35] Female Questions the use HPV vaccine for all The article approaches the topic of vaccination as a means that could be applied to the entire population, irrespective of age, sexual habits, sex and systemic condition. However, it makes it clear that in order to adopt this measure, it would be necessary to await the researches on the efficacy and safety of the vaccine for each population. Male — Indications for the H PV vaccine in adolescents 111 Mogensen (2009) [36] Female 9—26 years It emphasizes that prophylactic HPV vaccination is effective when used before sexual activity begins; however, there is no evidence about the efficacy of the vaccine in women over the ages of 25—26 years, which requires clinical studies.Male — Reiter et al. (2011) [37] Female 11—26 years Informs that after one year of the national recommendation for the use of prophylactic HPV vaccine for the male sex in the USA, only 2% of men received the vaccine.Male 9—26 years Eggertson (2012) [38] Female — The National Advisory Committee on Immunization says provincial governments should assess whether a human papillomavirus vaccination program for boys (9—26 years) is preferable to campaigns designed to increase female vaccination rates.Male 9—26 years Garnock-Jones and Giuliano (2011) [39] Female — Prophylactic HPV vaccination has shown a high degree of immunogenicity in the male sex within the age range of 9—26 years, and is well tolerated and recommended.Male 9—26 years Printz (2009) [40] Female 9—26 years Emphasizes the benefits of the vaccine for the male sex, for the prevention of genital warts and precursor lesions of penile cancer, in addition to informing that various doctors favor the use of the vaccine for the male sex (9—26 years) believing that the FDA will shortly support this position.Male 9—26 years Hibbitts (2010) [41] Female 9—26 years Supports the use of the vaccine for men, affirming that in the long term it would be an important factor in the prevention of diseases in women as well.Male 9—26 years Burki (2009) [42] Female — Points out the importance of elucidation as regards the benefits of the vaccine for the male sex, so that there were be greater HPV vaccine adherence by this sex. Male Support the vaccine for males. O’Connor (2009) [43] Female — The use of prophylactic HPV vaccine in the male sex, in addition to being of indirect benefit to women, prevents important lesions related to HPV, irrespective of sexual habits.Male Until age 26 Hull and Caplan (2009) [44] Female — Reinforces that the vaccination policy is still focused on the female sex, however, it should be offered to and encouraged for both sexes, making it more effective because of immunizing all possible carriers of the virus. Male Suggest the vaccine, but not for specific age 112 G .R. Soares et al. Table 2 (Continued) Author and year of publication Sex Indication for Main comments Paavonen (2010) [45] Female Priority: Young adolescents before their sexual debut In spite of the target population for receiving prophylactic HPV vaccine being girls before they become sexually active, it is believed that the inclusion of the male sex favors immunization of the population in general. Male Suggest the vaccine, but not for specific age Campos-Outcalt (2012) [46] Female — Discloses that the ACIP has recommended prophylactic vaccination against HPV to all men from 11 to 21 years and for those men from 22 to 26 years of age, who have sexual life with other men or are HIV positive.Male 11—26 years Smith et al. (2011) [47] Female Suggest the vaccine, but not for specific age Evaluates the prevalence of HPV in men, showing that the male sex presents high prevalence of both the high and low risk viruses, according to the population analyzed, the need for inclusion of the male sex in the vaccination programs is justified.Male Suggest the vaccine, but not for specific age Georgousakis et al. (2012) [48] Female 9—26 years Although men present fewer diseases related to HPV when compared with women, the prophylactic HPV vaccine must be considered for the male sex, since it present benefits not only to the men who receive it, but to their partners as well.Male 9—26 years Kubba (2008) [49] Female Suggest the vaccine, but not for specific age Defends the indication of prophylactic HPVB vaccine for adolescents of both sexes, because in addition to preventing lesions, it would also function as a strategy to make the immunization program successful, as there would be no exclusion of adolescents.Male 9—15 years Gilkey et al. (2012) [50] Female 11—17 year It was observed that the number of adolescents of the male sex who received the vaccine is three times lower tan those of the female sex. This suggests that the prophylactic HPV vaccine should be inserted together with the other vaccines in vaccination programs.Male 11—17 year Indications for the HPV vaccine in adolescents 113 Table 3 HPV vaccination in a selection of countries. Countries Vaccination system Target group (female) Vaccine Period Australiaa Routine 12—13 years 4-Valent Since 2009 Catch-up 12—26 years 4-Valent 2007—2009 Denmarka Routine, via GPs 12 years 4-Valent Since 2009 Catch-up, via GPs 13—16 years 4-Valent Since 2009 New Zealanda Routine 13 years 4-Valent School year: 2009—2010 and 2010—2011 Catch-up Girls: 14—20 years 4-Valent 2008—2011 Englanda Routine 12—13 years 2-valent Since school years 2008/2009 Catch-up 13—18 years 2-valent School years 2009/2010 and 2010/2011 USAa Routine Priority: 11—12 years 4-Valent Since 2007 Catch-up 13—26 years 4-Valent 2008—2011 Netherlanda Routine 12 years 2-Valent Since 2010 Catch-up 13—17 years 2-Valent In 2010 only Francea On prescription by physician Priority: 14 years 4-Valent Since 2007 Brazilb Routine 11—13 years 4-Valent Since 2014 a Ref. [10]. b H a t c 2 s f m a a s w s t f H 3 b d v w a O l A M v u t a a r v t g b v ( v o t Ref. [14]. PV vaccine by females beginning at the lowest ges of 8- to 14-years-old was 11.9%, and 50% of he articles recommended the use of the HPV vac- ine by females in the highest age group of 9- to 6-years-old. Other age groups were mentioned by even articles, but these age groups did not vary rom the age range of 8- to 26-years-old. Six articles entioned indications for the use of the vaccine mong males only, two articles did not specify an ge range for the use of the vaccine, and only a ingle article emphasized the indication for older omen (>26 years). However, other articles also uggested this possibility (Table 2). A similar pat- ern was observed regarding the recommendations or males; 9.5% of the articles recommended the PV vaccine for boys aged 9- to 15-years-old, and 0.9% of the articles recommend the vaccine for oys aged 9—26 years (Table 2). Seventeen articles id not mention the indication for the use of the accine by males, six articles indicated the vaccine ithout specifying an age group, and only a single rticle indicated another age group (11—17 years). ne article adopted a position against the prophy- actic use of the HPV vaccine by males (Table 2). D T t vailability of the vaccine to society any countries in which the authorities are con- inced of the safety and efficacy of the prophylactic se of the HPV vaccine are financing the adminis- ration of the vaccine to adolescents because these uthorities understand that vaccination represents preventive strategy with a favorable cost—benefit atio. Table 3 presents important data regarding the accination policies of several countries, including he adopted vaccination system, the age of the tar- et population, the type of vaccine applied (i.e., ivalent or quadrivalent) and the year in which the accination program began. We observed that 75% 6/8) of the countries adopted programs of routine accination of 12-year-old female adolescents, and nly two countries opted for the bivalent rather han the quadrivalent vaccination (Table 3). iscussion he main target populations of national immuniza- ion programs are adolescent girls regardless of H v t n e s 9 a c t m G N i w o f t m b l f t g t a c ( 1 a t c t t H o c w i b r w w s i m p t g 114 whether they have initiated sexual activity; how- ever, it is probable that many adult, sexually active women wish to receive the vaccine for their individ- ual benefit. Therefore, Wright et al. [11] considered the use of the vaccines to be acceptable in mod- ern clinical practice because these vaccines are immunogenic and safe for use in sexually active women. In Australia, young adolescents (10—17 years) are vaccinated through a project that is car- ried out in schools, and Australia is the first country to provide the vaccine via a public health program [12,13]. Many countries, including Brazil, offer pro- phylactic HPV vaccine to females, primarily those 12- to 13-years-old. In Brazil, a vaccination program for 11- to 13-year-old girls provided through the Sis- tema Único de Saúde (SUS) national health system was approved, and the campaign was scheduled to begin in March 2014 [10,14]. Studies have evaluated the recommendation that the vaccine be administered by physicians (i.e., general clinicians, pediatricians and gyne- cologists), and these studies have reported that a minority of these physicians provided their patients with guidance. This finding indicates that innumer- able clinical opportunities for vaccinations against HPV have been lost [15,16]. In the USA, despite the existence of national guidelines recommen- ding the vaccine for 11- to 26-year-old women, the proportions of physicians who indicate to their patients that they always recommend the vaccine ranges from 25.8% and 74.5% depending on the age range of the patients and the specialties of the physicians [17]. However, in another study that analyzed the indications for the use of the vac- cine in men, variation in the recommendations for the use of the vaccine also occurred with age; the vaccine was indicated for 11- to 12- (63.9%), 13- to 18- (93.4%) and 19- to 26- (92.7%) year-old males. Therefore, this medical recommendation is an important and consistent factor for use of the vaccine [16,17]. In India, it has been observed that doctors do not doubt the efficacy of the vaccine; therefore, the lack of time during consultations has been found to be the main justification for the non-indication of the vaccine. These doctors were required to pri- oritize other subjects during consultations or to discuss mandatory vaccines [18]. The author of the study explained that it is necessary for gynecolo- gists and obstetricians to explain the importance of the vaccine to women, not only to encour- age them to be vaccinated but also so that those women will have their future children vaccinated because women generally care for the health of their families [19]. Doctors believe that invest- ments in campaigns about the importance of the t [ d G.R. Soares et al. PV vaccine would make patients themselves seek accination [18]. A large portion of the authors indicated vaccina- ion for women from 11 to 26 years of age who are ot yet sexually active; i.e., those without previous xposure to the virus [3,6,20—28]. However, Bor- atto [29] indicated vaccination for all women aged —26 years regardless of sexual activity, and others uthors, such as Heideman et al. [30], included indi- ations for older women based on the perspective hat the vaccine is a safe and effective invest- ent [24,31]. The quadrivalent vaccine (HPV4; ardasil; Merck & Co, Inc., Whitehouse Station, J) is contraindicated for persons with histories of mmediate hypersensitivity to yeast and pregnant omen [32]. Despite the concern regarding the vaccination f girls who have not initiated sexual activity, i.e., requently children (9 years), authors believe that he administration of the vaccine at an early age ight reduce the immunity offered by the vaccine ecause it is used well before the phase of high evels of exposure to HPV infection [30], which requently occurs among 14- to 16-year-old girls; hus, the vaccine is needed for this latter age roup [33]. Another target population for vaccina- ion is young primiparous women (15—24 years of ge) among whom the prevalence of HPV in the ervical region is high. In one study group, 58.5% 176/301) of such women were HPV-positive, and 3% carried oncogenic types of HPV (i.e., HPV-16 nd HPV-18). This group of women is considered o be at high risk for the development of cervi- al cancer; therefore, vaccination is proposed to hese women during the post-natal consultation o prevent infections with the oncogenic types of PV [34]. The vaccine might prevent approximately 70% f the cases of cancer of the uterus and is thus onsidered a means of eliminating one of the most orrying female diseases and a disease with a high ncidence in India [5,21]. Thus, some authors have een encouraged to develop new research programs egarding the creation of effective vaccines for omen who have initiated sexual activity, those ho are infected by the virus, and for immuno- uppressed patients [20,35]. Others believe that nfection prevention programs for older women ust be of a different type because vaccination rograms are no longer economically feasible for hese women because the efficacies of such pro- rams have not been proven in clinical trials, and he virus is not highly prevalent in this age group 23,36]. Regarding males, although Nadal and Nadal [3] oes not agree about the benefits of the vaccine for I m p t a v m s p t h p A t t u [ i i f h t [ v t t b m f l h s r v o C D i i s e i T t v u n F N C N E N R [ [ [ [ [ [ ndications for the HPV vaccine in adolescents ales, in the USA, a recommendation for the pro- hylactic use of the HPV vaccine by men between he ages of 9 and 26 years was issued, but one year fter this recommendation was issued, the rate of accination among males of this age group was inimal (2%). This finding indicates the need for trategies to increase the use of the vaccine by this opulation; such strategies should include explana- ions about the disease, how it also affects men, ow it can be prevented and how the risk to sexual artners can be minimized [37—45]. Currently, the CIP states that the HPV vaccine must be adminis- ered to men between from 11- to 21-years-old and o men from 22- to 26-years-old who maintain sex- al relationships with other men or are HIV-positive 46]. HPV-16 is the most frequent type of infection n men irrespective of age; therefore further stud- es are needed to determine the best age group or the vaccination of the males, although some ave already stated that the appropriate age is he beginning of adolescence (10—15 years of age) 30,47]. In Australia, despite the belief that the accination of men would benefit to the population, here is still no program that finances the vaccina- ion of men, and the author of the relevant study elieves that it is not possible to vaccinate the ajority of the male population without financing rom the government [48]. Thus, recommendations in favor of the prophy- actic uses of the HPV vaccine and other vaccines ave made these vaccines more accessible to both exes of the adolescent populations, and such ecommendations represent a strategy for the pre- ention of pre-cancerous lesions in the genital and ropharyngeal regions [49,50]. onclusion espite the small divergences regarding the best ndications for the use of the HPV vaccine accord- ng to age, sex and sexual habits, all of the reviewed cientific articles maintained that the vaccine is an ffective means of prevention even when its use s restricted to a specific section of the population. he continuous study of articles is extremely impor- ant for our understanding of the properties of the accine and the benefits it provides to certain pop- lation groups, particularly those groups that are ot targets for this immunization. unding o funding sources. 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