The association of human papillomavirus vaccination with sexual behaviours and human papillomavirus knowledge: a systematic review.

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The association of human papillomavirus vaccination with sexual behaviours and human papillomavirus knowledge: a systematic review Victoria AH Coles, Ajay S Patel, Felicity L Allen, Sam T Keeping and Stuart M Carroll Int J STD AIDS published online 8 October 2014 DOI: 10.1177/0956462414554629 The online version of this article can be found at: http://std.sagepub.com/content/early/2014/10/08/0956462414554629

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Int J STD AIDS OnlineFirst, published on October 8, 2014 as doi:10.1177/0956462414554629

Review article

The association of human papillomavirus vaccination with sexual behaviours and human papillomavirus knowledge: a systematic review

International Journal of STD & AIDS 0(0) 1–12 ! The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0956462414554629 std.sagepub.com

Victoria AH Coles1, Ajay S Patel2, Felicity L Allen2, Sam T Keeping1 and Stuart M Carroll1

Abstract Since the 2008 introduction of the human papillomavirus (HPV) vaccination programme for adolescent girls in the UK, parents and other groups have expressed fears that immunisation condones sexual activity, promotes promiscuity and encourages risky sexual behaviour. This study aimed to explore whether HPV vaccination programmes have increased knowledge surrounding HPV and associated disease and whether uptake has influenced sexual behaviour. MEDLINE, Embase, Cochrane Library and PsycINFO electronic databases were interrogated. Studies of behaviour, attitudes and knowledge associated with HPV vaccination (or vaccination intent) in subjects of any age and gender in programmes reflective of UK practice were included in the review (n ¼ 58). The evidence regarding the association of HPV vaccination with high-risk sexual behaviour was varied, primarily due to the heterogeneous nature of the included studies. Young females typically exhibited better knowledge than males, and vaccinated respondents (or those with vaccination intent) had higher levels of knowledge than the unvaccinated. However, knowledge surrounding HPV and genital warts was generally poor. This review highlights the need to provide effective education regarding the HPV vaccine and HPVassociated disease to adolescents of vaccination age, nurses, teachers, parents and guardians to ultimately allow informed decisions to be made regarding receipt of the HPV vaccine.

Keywords Human papillomavirus, vaccination, sexual behaviours, genital warts Date received: 4 June 2014; accepted: 15 September 2014

Introduction Human papillomavirus (HPV) is a highly prevalent sexually transmitted infection (STI) which has been identified as a causative agent in the development of cervical cancer.1 There are two HPV vaccines available, a bivalent vaccine and a quadrivalent vaccine. Both protect against persistent infection with HPV 16 and 18, which cause 70% of cervical cancers2 and have been shown in clinical trials to be 94.9%–98.2% efficacious against moderate- to high-grade cervical lesions caused by these subtypes, after an average of 3.3–3.6 years’ follow-up.3,4 The quadrivalent vaccine also protects against persistent infection with HPV 6 and 11,3 which cause 90% of genital warts cases.5 Now that these effective and well-tolerated vaccines are available, various countries have made the decision to institute national vaccination programmes.

In the UK, an HPV vaccination programme was introduced in 2008 for adolescent girls,6 with the primary aim of preventing cervical cancer. Initially, the bivalent HPV vaccine was used in the UK’s routine vaccination programme, but in 2012, this was replaced with the quadrivalent vaccine. Data representing all primary care trusts in England indicate that uptake of the HPV vaccine in 12- to 13-year-old girls from September 2012 to August 2013 was 86.1% for all three doses.7 Some countries, such as Australia and the US, have 1 2

Sanofi Pasteur MSD, Maidenhead, UK Abacus International, Bicester, UK

Corresponding author: Victoria AH Coles, Sanofi Pasteur MSD, Mallards Reach, Bridge Avenue, Maidenhead, Berkshire SL6 1QP, UK. Email: [email protected]



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extended the recommendation to include boys in the immunisation programme, due to the protection offered against persistent HPV infection, anogenital pre-cancerous lesions and genital warts.8,9 Given that HPV is primarily transmitted through sexual intercourse, there is fear among parents and other groups that the UK HPV vaccination programme condones sexual activity, promotes promiscuity and encourages other risky sexual behaviour.6,10,11 The current review aims to address such concerns and to determine the impact immunisation against HPV has on sexual behaviour and awareness of HPV (and associated diseases) in countries with HPV vaccination programmes reflective of UK practice.

Methods This systematic review was conducted in accordance with a pre-defined protocol and PRISMA guidelines.12 Search strings were used to interrogate the MEDLINE, Embase, Cochrane Library and PsycINFO electronic databases for papers published between January 2003 and May 2013. Hand searches were conducted for meetings/congresses of interest held between January 2010 and May 2013 and for other grey literature published since January 2003. The meetings/congresses searched were: The International Society for Sexually Transmitted Diseases Research (ISSTDR), British Association for Sexual Health and HIV (BASHH), European Research Organisation on Genital Infection and Neoplasia (EUROGIN), International Papillomavirus conference (IPC), STI and AIDS World Congress, and the International Association for Adolescent Health World Congress. Grey literature sources searched were: Public Health England (PHE; formerly the Health Protection Agency), Department of Health (UK), Joint Committee on Vaccination and Immunisation (JCVI), European Centre for Disease Prevention and Control (ECDC) and the National Institute for Health and Care Excellence (NICE). Only English language publications were reviewed. Key inclusion criteria were: respondents of any age and gender receiving HPV vaccine or with future intent to be immunised, and studies with 100 participants. Geographical regions included were Europe, Canada, Australia and New Zealand, as the vaccination programmes in these areas are most similar to that in the UK. Studies from the US were excluded, as access to HPV vaccines is not comparable with that in the UK. The school-based vaccination programme in the UK results in high vaccine uptake nationwide in the routine cohort of 12- to 13-year-old girls (86.1% for three doses in 2012/13),7 whilst in the US, coverage rates are much lower; in 2012, even among females aged 17 years (the most highly vaccinated age group), only

44.5% had received three doses.13 Furthermore, HPV vaccines are administered in a health care setting in the US and are funded predominantly through private health insurance, only being provided free of charge to those who are Medicaid eligible, uninsured or underinsured. Outcomes considered were: sexual activity-related behaviours (sexual debut, number of sexual partners, levels of sexual activity, promiscuity, use of contraception or other safe sex practices, other risky sexual practices, risk compensation); clinical outcomes (history of genital warts, diagnoses of other STIs, visits to genitourinary medicine (GUM) or sexual health clinics or other health professionals (gynaecologists, general practitioners, contraceptive counselling)); perceptions (including vulnerability to HPV infection, perceived vulnerability to HPV-associated diseases and efficaciousness of vaccine); knowledge and awareness of issues (surrounding contraception, safe sex practices, HPV infection and genital warts, Pap smear (cervical screening) and cervical cancer, receipt of HPV vaccine and availability of sexual health services). Included studies were non-randomised controlled trials or randomised controlled trials (RCTs). Citations yielded by the searches were imported into a database and assessed based on title and abstract. Full publications of potentially relevant citations were examined using the pre-defined eligibility criteria and verified by a second reviewer. Disputes were resolved via discussion with a third party until a consensus was reached. Data from relevant publications were extracted into a data extraction table (Microsoft ExcelÕ ) and double-checked by a second reviewer. RCTs were quality assessed using the methodology checklist from the NICE Guidelines Manual 200914; case–control, cohort and longitudinal observational studies were quality assessed using Chambers criteria15 and cross-sectional studies using modified Chambers criteria.15 Details of the inclusion and exclusion criteria, extracted studies and their main results can be found in Appendices 1 and 2. Details of the search strings, grey literature searches, studies excluded at the full text stage and quality assessment of included studies can be found in Optional Appendices 1–3.

Results Study selection A diagram illustrating the flow of studies through the systematic review process is provided in Figure 1. The final dataset included 58 studies: two RCTs16,17 and 56 non-RCTs. Of the non-RCTs, three contained data from longitudinal studies,18–20 52 contained data



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Figure 1. Systematic review PRISMA flow diagram. yOf the 18 conference abstracts, 16 were included from formal conference proceeding searches and two from electronic database searches.

from cross-sectional studies and one publication reported details of both a cross-sectional and longitudinal study.6 Of the included studies, 11 were UKbased,6,10,21–29 nine were from Australia,17,30–36 seven from Canada,16,20,37–41 five each from Italy42–46 and Sweden,47–51 four from the Netherlands,52–55 three

each from France56–58 and Greece,59–61 two each from Germany,62,63 Hungary19,64 and Turkey,65,66 one each from Denmark,67 Finland,68 Ireland69 and New Zealand,70 as well as a multinational study.71 The following items were reported/recorded: sexual debut;6,10,16,22,31,33,49,52,54,56,60,61,63,66,68 number of



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sexual partners/levels of sexual activity/promiscuity;6,17,22,25,39,40,42,49,52,54,65,72 use of contraception or other safe sex practices/risky sexual practices (not including risk compensation);6,25,29,33,39,44–51,54,57,60,61,69,72 risk compensation;22,23,28,29 previous history of genital warts;39 previous diagnoses of other STIs, excluding HPV infection/genital warts;22,27,28,39,54,72 previous visits to other health professionals;59,60,65,66 perceptions surrounding vulnerability to HPV infection;19,22,25,33,36,38,42,43,48,50,53,63,64,67,68,70 perceptions surrounding efficaciousness of HPV vaccine;19,25,31,32,42,43,49,50,63,64,70 knowledge/awareness of issues surrounding contraception or other safe sex practices;24,30,37,42–46,52,57,64,71 knowledge/awareness of issues surrounding HPV infection and genital warts;16,17,22,24,26,30,31,35–39,43,44,48,50,52,54,62–64,66,68,69,71 knowledge/awareness of issues surrounding Pap smear (cervical screening) and cervical cancer;19,20,30,38,44–46,49,50,52,54,57,64 knowledge/awareness of issues surrounding receipt of HPV vaccine;17,21,30,31,35,36,41,42,45,56,59,63,64,69 knowledge/ awareness of access to sexual health services.22

Sexual activity-related behaviour Sexual debut was reported in 15 studies;6,10,16,22,31,33,49,52,54,56,60,61,63,66,68 however, the definition was variable, referring to anything from first sexual contact to first full intercourse. Perhaps as a consequence, the evidence surrounding early sexual debut and HPV vaccination was conflicting. Nine studies compared sexual debut in HPV vaccinated (or intending to be vaccinated) and unvaccinated (or not intending to be vaccinated) individuals.6,22,33,49,52,54,56,60,66 Two studies revealed that some adolescents believe HPV vaccination may lead to an earlier age of sexual debut,10,68 whereas there was no association in another four studies.6,22,54,56 In two studies, girls reaching sexual debut were significantly more likely to receive HPV vaccination in the future,54,66 but a third study found this not to be the case.52 No significant difference was observed between men who had and had not reached sexual debut with regard to intention to be vaccinated.66 Only one study revealed a significant association between not having reached sexual debut and increased uptake of the HPV vaccine.60 Sexual debut appeared to have been reached in significantly more vaccinated than unvaccinated female university students aged 18–30 years from one educational establishment in Australia.33 This finding was replicated in a Swedish study of young adults aged 18–30 years which found that individuals who had not debuted were less likely to be HPV vaccinated.49 Those sexually debuting at a younger age also had the

highest willingness to be vaccinated and to pay for the vaccine.49 Although both studies33,49 suggest that earlier sexual debut is associated with greater uptake of HPV vaccination, neither study investigated whether immunisation led to sexual debut, and in both cases, participants were older than the target age for HPV vaccination in the UK. Therefore, although a correlation was observed, causation cannot be inferred, and it cannot be concluded that HPV vaccination leads to earlier sexual debut. Rather, it appears that sexually active individuals may be more proactive regarding the adoption of preventative practices against STIs. Conflicting evidence was provided in 12 studies regarding the association between HPV vaccination and sexual activity.6,17,22,25,39,40,42,49,52,54,65,72 An equal number of studies (n ¼ 6) demonstrated that being sexually active (including number of sexual partners) was17,25,49,54,65,72 and was not6,22,39,40,42,52 associated with vaccination status or intention to be vaccinated. Outcomes regarding contraception and safe or unsafe sexual practices were captured in 20 studies;6,23,25,29,33,39,44–51,54,57,60,61,69,72 of these, 18 compared vaccinated and unvaccinated individuals or considered perceptions surrounding vaccination.6,23,25,29,33,39,44–46,48–51,54,57,60,69,72 The majority of studies (12/18) found that vaccinated individuals (or those with an intention to be vaccinated) were not less likely to use contraceptives than the unvaccinated (or without an intention to be vaccinated).6,29,33,39,44–46,48,49,54,60,72 One such study demonstrated that women (aged 20–29 years) who received free HPV vaccination were statistically significantly more likely to be currently using hormonal contraception than unvaccinated peers.72 Six (6/18) studies indicated that safe sex practices (including condom use) were less likely (or perceived less likely) to be adopted by vaccinated individuals.25,48,50,51,57,69 In a UK-based study of 16- to 19-year-old girls, 43% of participants thought ‘girls in general’ would be more likely to have sex or unprotected sex if they had the HPV vaccine.25 In older females (20–64 years) from Ireland, a much lower percentage (14%) felt that vaccination could encourage unprotected sex.69 Although there appears to be a perception that vaccination is associated with more risky sexual practices, outcomes data are inconclusive. For example, in a UK-based study including females aged 16 years, 37.5% agreed that HPV vaccination would encourage ‘girls in general’ to have unprotected sex.23 However, with regard to their own sexual behaviour, a much smaller proportion (only 8.4%) believed that they would partake in unprotected sex after vaccination.23 Unsafe sexual practices in response to HPV vaccination may be described as ‘risk compensation’, i.e. behavioural adjustments made by an individual in



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response to their perceived level of risk. If an intervention creates a feeling of safety, which in turn leads to excess risk elsewhere, the overall protective effect of the original measure is reduced.73 Five UK-based studies were identified which specifically considered risk compensation.6,22,23,28,29 Two studies evaluating girls who were eligible for the HPV vaccine implied that vaccinated (versus unvaccinated) individuals were taking fewer sexual risks,28,29 although risk compensation was reported in a minority (1.5%).29 One study indicated that vaccinated girls were no more likely to have changed their condom use or increased their total number of sexual partners when compared with unvaccinated peers.6 In another study, a low HPV knowledge score was identified as a significant predictor of personal risk compensation levels among adolescent girls.23 Finally, in women aged 16–18 years with a stronger belief that provision of sexual health services or STI vaccines would lead to more risky sexual behaviour, bivariate analysis demonstrated that uptake of HPV vaccination is less likely.22

Clinical outcomes Although four studies were conducted in a GUM/ sexual health clinic setting,27–29,35 visits to such establishments were not captured as an outcome in any of the identified studies. Three studies reported outcomes concerning visits to health care professionals other than GUM/sexual health clinics.60,65,66 Two of these studies reported significantly greater willingness to receive the HPV vaccine among individuals who had previously visited an obstetrics and gynaecology physician.60,66 In the third study, acceptance of the vaccine was significantly greater among 17- to 80-year-olds with a history of an abnormal versus normal Pap smear test.65 No studies considered a history of genital warts in females. Six studies reported on outcomes related to the association of vaccination with a history of STIs other than HPV.22,27,28,39,54,72 Three studies demonstrated no significant difference concerning STIs between the vaccinated (or intending to be vaccinated) and unvaccinated (or not intending to be vaccinated).22,39,54 However, for vaccinated versus unvaccinated (or partially vaccinated) women, one study found that a prior STI diagnosis was more likely.72 In contrast, two studies reported lower rates of chlamydia in women who received full vaccination.27,28

Perceptions Sixteen studies reported outcomes surrounding beliefs of vulnerability to HPV infection.19,22,25,33,36,38,42,43,48,50,53,63,64,67,68,70 In four of the

16 studies, some respondents appeared unconcerned about infection with HPV or HPV-associated disease,22,36,50,64 for example, 17.3% of 15- to 16-yearold Swedish schoolchildren did not believe they would ever be infected.50 However, stronger intentions to accept the HPV vaccine were significantly related to greater worries about STIs other than HPV.22 Perceptions relating to cervical cancer were recorded in two studies.36,64 In Hungary, 19.4% of study participants (aged 12–19 years) did not believe that HPV causes cervical cancer,64 and nearly one-third (31%) of 18- to 28-year-olds in an Australian study were ‘not really concerned about getting cervical cancer’.36 Three out of four studies considering gender differences and perceived susceptibility to HPV48,50,63,70 found that males were less likely to be concerned about being infected with HPV50,70 or STIs in general.48 One study noted that significantly more males than females cited their perception of ‘not being at risk of contracting HPV’ as a reason for non-vaccination.63 Five studies reported no association between perceived severity of HPV or HPV-associated disease and vaccine uptake.25,33,38,67,68 Surprisingly, considering the known association with HPV, only 3% of 16- to 20year-old females and 7.9% of those aged 21 to 26 in Denmark mentioned ‘high risk of cervical cancer’ as a primary reason for accepting HPV vaccination and only 5% and 4%, respectively, cited ‘high risk of HPV infection’.67 In contrast, two studies identified a link between vaccination intent and perceived HPV infection risk.42,53 Significant predictors of willingness to receive the HPV vaccine were a high perceived risk of HPV infection and of developing cervical cancer.42 In two Australian studies, 95.8% of individuals stated that protection against HPV infection and cervical cancer was a primary reason for vaccination,31 and nearly half (43.1%) of those against HPV vaccination would be more amenable if it also prevented genital warts.32 Both currently available HPV vaccines protect against persistent infection with HPV 16 and 18, which cause 70% of cervical cancers.2 The quadrivalent vaccine also protects against persistent infection with HPV 6 and 11, which cause 90% of genital warts.5 Eleven studies reported beliefs related to efficaciousness of the vaccines against HPV infection or HPV-associated disease.19,25,31,32,42,43,49,50,63,64,70 The majority of studies (6/11) found that willingness to be vaccinated or actual uptake of the vaccine was associated with the belief that it would be efficacious. However, one study reported that 6% of women wrongly believed that they would be fully protected against cervical cancer by the HPV vaccine49 and that 13% of women and 15% of men believed it would fully protect against genital warts.49 In contrast, one



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Hungarian study reported that although 86% of included adolescents (12- to 19-year-olds) believed in the general effectiveness of vaccinations, 27% did not believe a vaccine can prevent cervical cancer.64

Knowledge and awareness Knowledge and awareness of HPV infection prevention through the use of contraception and safe sex practices was reported in 12 studies.24,30,37,42–46,52,57,64,71 Poor knowledge was noted in 10/12 studies,24,30,37,42,44–46,52,64,71 with seven studies demonstrating that a large proportion of respondents were unaware that condom use reduces the risk of HPV transmission24,30,42,44–46,71 and three studies reporting that a large number of individuals incorrectly believed that condom use completely prevented HPV transmission.37,52,64 A reasonable awareness of issues surrounding HPV and contraception use was apparent in two studies comparing vaccinated and unvaccinated individuals.43,57 One study reported no impact of HPV vaccination status on knowledge and behaviours about STI prevention57 and the second demonstrated better HPV prevention knowledge in unvaccinated versus vaccinated girls.43 Twenty-five studies reported on knowledge and awareness of issues surrounding HPV infection or genital warts.16,17,22,24,26,30,31,35–39,43,44,48,50,52,54,62–64,66,68,69,71 Poor levels of general knowledge, knowledge gaps and misconceptions regarding HPV infection and disease were commonly reported.22,24,26,30,35,43,44,48,50,63,65,66 High levels of knowledge across all aspects of HPV infection and disease were not reported in any studies. Young females exhibited better knowledge than males in several studies,30,52,62–64,71 although a Swedish study reported no gender differences.48 Knowledge levels by vaccination status were considered in 11 studies.22,24,30,31,37,39,52,54,62,65,66 Nine of these reported that vaccinated respondents (or those with vaccination intent) had higher levels of knowledge versus the unvaccinated.24,30,31,37,39,54,62,65,66 Only two studies reported no significant association between knowledge levels and intention to be vaccinated.22,52 Knowledge relating to the Pap smear (cervical screening) and cervical cancer was captured in 13 studies,19,20,30,38,44–46,49,50,52,54,57,64 with awareness typically recorded as poor (eight studies).30,38,45,46,49,50,57,64 Good awareness of the need for regular Pap smears after vaccination was noted in one Italian study (93.3% of girls).44 Six studies reported on knowledge of issues surrounding Pap smear and cervical cancer by vaccination status.20,30,46,52,54,57 Of these, four reported significantly greater awareness among vaccinated versus unvaccinated individuals.20,30,46,57 One Dutch study noted that awareness of the Pap smear programme was significantly lower in vaccinated versus

unvaccinated girls, although after being informed of the programme, they were significantly more inclined to participate.54 Another Dutch study demonstrated that knowledge of cervical cancer and the Pap smear programme was not significantly associated with acceptance of HPV vaccination.52 Fourteen studies reported on respondents’ knowledge of issues surrounding receipt of the HPV vaccine.17,21,30,31,35,36,41,42,45,56,59,63,64,69 Eleven of these studies highlighted generally low levels of knowledge regarding the HPV vaccine,17,30,31,35,36,42,45,56,59,64,69 whereas reasonable knowledge levels were noted in three studies.21,41,63 Misconceptions were reported surrounding HPV vaccination and cervical cancer,31,36 immunisation before sexual debut,17,30 lack of awareness of the vaccine,35 vaccine efficacy42,45 and its preventative nature.42 One study of Italian adolescents also reported that 10.6% mistakenly believed that HPV vaccination protected against HIV.45 Two studies reported knowledge of HPV vaccine by vaccination status (or vaccination intention).36,59 An Australian study reported that unvaccinated women were more unsure or more likely to think that the vaccine could be used therapeutically versus vaccinated counterparts.36 However, there was no difference between the vaccinated and unvaccinated as to the proportions of respondents who incorrectly thought that the vaccine can prevent all cervical cancers.36 A Greek study of female university/technological institute students reported that, in multivariate analyses, vaccine uptake was significantly associated with a high level of knowledge.59 Only one study reported outcomes concerning knowledge and awareness of sexual health services.22 This UK study (in women aged 16–18 years) demonstrated, via multivariate analysis, that individuals with greater support for young people’s sexual health services had stronger intentions to accept vaccination.22

Discussion Misunderstanding has surrounded the UK HPV vaccination programme since its inception in 2008. The fears of parents and guardians need to be addressed to allow them to provide informed consent for HPV vaccination prior to the sexual debut of adolescent girls, to ensure maximum impact of immunisation and reduce the risk of genital warts and cervical cancer. The current systematic review is, to our knowledge, the first to investigate the association between HPV vaccination and sexual behaviour. Studies from Europe, Canada, Australia and New Zealand, identified in the current review, provide limited evidence to support or refute the hypothesis that HPV vaccination is associated with risky sexual



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behaviours, primarily because few studies were designed to explicitly assess sexual activity outcomes. The majority of studies reported on HPV knowledge and vaccine acceptability rather than the correlation between HPV vaccination and sexual behaviour, with the exception of a large cross-sectional and longitudinal study of 16- to 18-year-old girls in the UK, which showed that the HPV vaccine had no influence on sexual activity, condom use or number of sexual partners.6 Where considered, studies (n ¼ 5, all UK-based) were neutral or supportive of the hypothesis that HPV vaccination did not cause risk compensation in sexual behaviour.6,22,23,28,29 This is further supported by two recent studies, published since completion of the current systematic review. A UK-based study by Bowyer et al.74 demonstrated that there was no association between HPV vaccine uptake and age of sexual debut or sexual activity in adolescent girls, and a Scandinavian study found that women who were vaccinated before or at the same age as sexual debut did not subsequently engage more in sexual risk-taking behaviour than those who did not receive the HPV vaccine.75 Several studies reported significantly greater levels of HPV disease-related knowledge in individuals who had received the HPV vaccine versus unvaccinated peers. However, the general level of knowledge was reported to be low, and misconceptions were commonplace, with some individuals even confusing HPV and HIV. Variability amongst different demographics, such as religion, ethnicity, culture and socio-economic status, may influence the impact of educational interventions. As expected, knowledge was greater in females than males and is likely to consistently improve as each year group receiving the vaccine becomes aware of HPV and HPV-associated disease. Bowyer et al.74 recently reported that girls with a higher knowledge of HPV and the HPV vaccine at baseline were significantly more likely to have received the vaccine at follow-up a year later (p ¼ 0.027), demonstrating the importance of adequate education regarding the vaccination. An unexpected reduction in genital warts cases, particularly in females, has been observed since the introduction of the bivalent HPV vaccine in England in 2008,76,77 which may be due to increasing HPV knowledge and awareness of STIs. However, a more recent study78 of sexually active young women screened for chlamydia demonstrated a decline in infections with HPV 16 and 18 after immunisation with the bivalent HPV vaccine, but not in infections with HPV subtypes causing genital warts. The sample population in the latter study is unlikely to be a true representation of adolescents receiving the HPV vaccine as it was limited to sexually active women undergoing screening for chlamydia and may therefore represent those engaging

in high-risk sexual behaviours. Very recently, a group of UK-based researchers presented data suggesting an alternative explanation for the reduction in genital warts observed during the period of bivalent vaccine use. The authors proposed that the introduction of asymptomatic screening pathways over a similar time period may account for a considerable proportion of the reduction in warts diagnoses seen and estimated that failure to examine asymptomatic patients may lead to up to 12.26% of warts diagnoses being missed.79 Nevertheless, questions remain, and further studies are warranted to explore the association between the bivalent vaccine and cases of genital warts. In contrast, robust evidence from Australia, one of the first countries to implement a nationally funded quadrivalent vaccination programme, demonstrates that since its 2007 introduction, there has been a significant decline in the proportion of women diagnosed with genital warts.80 The absence of genital warts in women who took part in the Australian HPV vaccination programme indicates that the quadrivalent vaccine is efficacious in a real-world setting.80 Although education can bring about an increased understanding of HPV and associated disease, knowledge gaps exist among adolescents, and influencing attitudes towards HPV vaccination, use of condoms and Pap smear screening appear challenging. This highlights the need to ensure that educational messages are appropriately framed; in particular, making information accessible to sexually inexperienced adolescents. An opportunity also exists to educate teachers and school nurses responsible for the delivery of the HPV vaccine programme, to arm them with a superior level of knowledge as well as to make them aware that there may be misconceptions surrounding vaccination. This would empower them to answer questions from adolescents regarding HPV and to know which resources are appropriate to use. This systematic review is subject to limitations. First, the included studies were highly heterogeneous, and there is a paucity of data from longitudinal or followup studies; most evidence is derived from cross-sectional surveys. Such surveys are also prone to bias such as recall and social desirability bias. The included studies varied considerably, particularly regarding demographics (e.g. university students, adolescents), and therefore care should be taken when generalising their results. Furthermore, vaccinated and unvaccinated populations are likely to be fundamentally different; in some cases, the reasons for non-vaccination may also affect current or future sexual behaviour (e.g. religious or cultural views and social deprivation). Although the ultimate aim of this systematic review was to look at the impact of being immunised, due to the paucity of data, it was necessary to include evidence



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of an empirical (i.e. behaviour of the vaccinated) and subjective (beliefs of those intending to be vaccinated) nature. Empirical data are of course preferable and considered more robust; however, in the absence of sufficient studies reporting such data, those investigating beliefs and intentions may also need to be considered. In addition, it could be argued that the presence of an HPV vaccination programme and exposure to any related information could be having an impact on knowledge, attitudes and sexual behaviour even in the unvaccinated. Correlations reported in the published literature do not necessarily indicate causation and should be interpreted with care. Additionally, the systematic review did not consider qualitative (thematic analysis) studies or those reporting data from the perspective of parents, guardians or health care professionals. The inclusion of US-based studies would have provided further data; however, studies from the US were excluded due to large differences in vaccine access and procedures between the US and the UK. Evidence suggests that educational interventions may improve health-protective behaviours and that adolescents are receptive to such methods. For example, in 2010, Miyamoto and Chevalier81 indicated that causal evidence exists for the relationship between education and improvements in mental health and drinking in the UK and US and that education can raise the level of individuals’ health whilst helping to reduce health inequalities. In the area of sexual behaviour, educational interventions may encourage sexual risk reduction and have the potential to reduce HPV transmission and cervical cancer incidence.82 Other educational interventions in the UK have been designed to encourage healthy behaviour; the ‘Change4Life’ campaign has successfully managed to help parents make the association between behaviours that lead to excess weight gain and poorer health outcomes in their children.83 Drink-driving campaigns, such as ‘THINK!’ have successfully facilitated sustained behavioural changes and are estimated to have saved 2000 lives and prevented over 10,000 serious injuries, with a value to society of £3 billion.84 The Department of Education has stated that sex and relationship education is an important part of personal, social, health and economic (PSHE) education programmes in UK schools; such programmes are designed ‘to equip pupils with a sound understanding of risk and with the knowledge and skills necessary to make safe and informed decisions’.85 Furthermore, PHE support public education and social marketing campaigns to help people take better control of their well-being, including sexual health.86 The schools-based vaccination programme in the UK provides an ideal opportunity for knowledge building. There is a need for educational establishments and the Department of Health to work together to maximise the opportunity

for success, including educating males on the issues surrounding HPV. The impact of tailoring educational messages for girls receiving the HPV vaccine needs to be evaluated, given that the influence of different messages may vary between demographic groups. Unfortunately, the evidence identified in the current analysis does not allow firm conclusions to be drawn regarding the association of HPV vaccination with sexually risky behaviour in the UK or similar settings. In the US, HPV vaccination in girls aged 11–12 years has been shown not to be associated with increased sexual activity-related outcome rates.87 A similar retrospective study of linked vaccine records and clinical obstetrics, gynaecology and GUM would be of value to objectively ascertain the impact of HPV vaccination on sexually risky behaviours in the UK. Although levels of knowledge surrounding HPV were typically reported as low in the current review, there did appear to be a trend towards greater levels of knowledge in young females versus males and in vaccinated versus unvaccinated individuals. This suggests that HPV vaccination may influence, or be influenced by, awareness of HPV. Results from a US study in college-aged women support this and demonstrate that there is a statistically significant relationship between knowledge, attitudes and intention to be vaccinated.88 The current review highlights some of the misconceptions surrounding HPV vaccination and the need to provide effective education regarding immunisation and HPV-associated disease. Adolescents need clear messages to ensure that the vaccine is seen as complementary to – and not a replacement for – safe sex. Furthermore, improving HPV education for adolescents, nurses, teachers, parents and guardians should ultimately allow informed decisions to be made surrounding receipt of the HPV vaccine. Conflict of interest VC, SK and SC are employees of Sanofi Pasteur MSD, which holds a marketing authorisation for one of the HPV vaccinations in use in the UK. AP and FA have received consultancy fees from Sanofi Pasteur MSD.

Funding This work was funded in full by Sanofi Pasteur MSD.

References 1. Gottvall M, Tyden T, Hoglund AT, et al. Knowledge of human papillomavirus among high school students can be increased by an educational intervention. Int J STD AIDS 2010; 21: 558–562. 2. Smith JS, Lindsay L, Hoots B, et al. Human papillomavirus type distribution in invasive cervical cancer and highgrade cervical lesions: a meta-analysis update. Int J Cancer 2007; 121: 621–632.



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