Equity in human papilloma virus vaccination uptake?: sexual behaviour, knowledge and demographics in a cross-sectional study in (un)vaccinated girls in the Netherlands

Human papillomavirus (HPV) infection is one of the most common sexually transmitted infections (STI) worldwide. By the age of 50, about 80% of sexually active women will acquire HPV [1‐3]. Most infections are transient and around 90% clears within two years [4, 5]. However, a persisting high-risk HPV infection is the most important risk factor for the development of premalignant cervical intraepithelial neoplasia (CIN1-3) and cervical cancer [6].

Since 2006, a quadrivalent vaccine that induces protection against HPV types 6, 11, 16 and 18 (Gardasil®), and in 2007 a bivalent vaccine against HPV type 16 and 18 (Cervarix®) are available. Both have shown an efficacy of >90% in preventing CIN2/3 [7, 8].

In the Netherlands, the bivalent HPV vaccine (Cervarix®) targeting 12-year-old girls became part of the National Immunisation Program in 2010. In 2009, girls aged 13 to 16 years were offered this vaccine during a “catch-up” vaccination program where the uptake amounted to 52% [9]. HPV vaccination uptake depends on diverse factors. In the United Kingdom, schoolgirls from ethnic minorities had a lower vaccine uptake and in the United States, girls with lower socio-economic status were less likely to take up the full 3 doses of the vaccine [10, 11]. In the Netherlands, a cervical cancer screening program runs since 1976. Currently, the program provides organized cervical cytological screening every five years for women aged 30–60 years. In 2005, there was a 65% attendance to the cervical screening program [12]. However, when including opportunistic screening figures, the overall coverage for cervical screening amounted to 77% nationwide [13]. It has been shown that in the Netherlands, socio-economically disadvantaged women and women of non–Dutch nationality attend the national cervical screening program less frequently [14]. More than half of the cervical cancers are diagnosed in women who do not attend the Dutch screening program [15, 16]. Reducing the occurrence of cervical cancer might thus be hampered if girls who tend to decline HPV vaccination now are also screened less often in the future. This might lead to inequity, i.e. unequal fairness or justice in the way people are treated.

Prior to introduction of vaccination, some studies have reported on girls’ intention to be vaccinated [17‐19]. However, little is known about the characteristics of girls in relation to actual HPV vaccination uptake [20, 21]. This study aims to explore differences between vaccinated and unvaccinated girls with regard to characteristics such as education, ethnicity, (sexual) risk behaviour and knowledge of HPV. Understanding the features of these two groups could provide insight in future vaccine and screening targeting efforts.

This population-based study is one of the first that examined actual determinants for individual vaccine uptake instead of willingness to be vaccinated. Vaccinated and unvaccinated girls were comparable with regard to education, education of parents, ethnicity, most sexual risk behaviour and had similar scores on knowledge of HPV infection and HPV transmission. They differed with respect to characteristics such as urbanisation degree, religion, contraceptive use, number of lifetime sexual partners and importantly, their opinions on the use of condoms after HPV vaccination and the protection of vaccination against all HPV types.

Studies in the Netherlands have shown that women who are non-Dutch nationals and have a lower socio-economic status are less likely to participate in the cervical cancer screening program [14, 15]. These risk factors for non-attendance were not observed in this study for girls who chose not to be vaccinated. We found no relationship between uptake and ethnicity, nor education of the girl or their parents or SES score (both indicators of socio-economic status), which could suggest that the two programs might strengthen each other Another Dutch study also concluded that vaccination and screening (assessed by reported screening behaviour of the mother) complement each other to a large extent [25].

Religion has influenced vaccination decision-making process since the beginning of vaccination efforts [26]. Anti-vaccination proponents were most common in countries with a high proportion of Protestants [27]. In our study, identifying as a Protestant Christian was related to a lower vaccination uptake, as opposed to identifying as a Catholic or not following a religion. In addition to specific religious groups among the Protestant Christians (such as Orthodox reformed), the reluctance towards HPV vaccination might be extended amongst a broader group of Protestant Christians because of the link with a sexually transmitted infection. Participation in screening programs has not been found to be lower in Dutch regions with higher proportion of religious groups [25], highlighting again the possible complementarity between screening and vaccination.

Contradicting results regarding the influence of HPV knowledge and perceptions on vaccination uptake have been reported [28]. Consistent with a Dutch study on acceptance of HPV vaccination [29], we obtained no differences on vaccination uptake with regard to the general HPV knowledge score, nor on the HPV transmission knowledge score. Regardless of vaccination status, as many as 80% of the girls knew of the relationship between HPV and cervical cancer, which was similar to some other studies (81% Lenselink CH et al. [29], 84% Gerend MA and Shepherd JE [28], 85-93% Marlow LA et al. [30] program.

In general, only 50% of the young girls in our study recognised that after an HPV vaccination it is still indicated to participate in the cervical cancer screening program (which takes place from age 30 onwards in the Netherlands). This fact has also been reported by Bowyer HL et al. [31] amongst a group of 15–16 year old girls, where only 47% was aware cervical screening is still necessary after vaccination. We also found that vaccinated girls were less aware of the fact that vaccination does not protect against all HPV types. The continued importance of cervical screening in the Netherlands has to be emphasised along with the benefits of HPV vaccination. The finding that vaccinated girls report more often that their mothers participate in the cervical cancer screening program seems somewhat contradictory to their lower awareness about this program. Paulussen TG et al. [32] reported that a major part of the population does not make a well thought decision with regard to vaccinations in the regular National Immunization Program). These parents regard vaccination as self-evident. Similarly, this might be so for a part of mothers with regard to participation in screening, which possibly results in less discussion on the topic and thus less knowledge among their daughters.

In our study, only 2-3% reported that HPV vaccination had changed their sexual behaviour in the first year after vaccination. However, Marlow LA et al. [33] found that one-third of adolescent girls interviewed, thought that HPV vaccination would make girls in general more likely to have unsafe sex. Swedish high-school students did not think it that they themselves would engage in more unsafe sex after HPV vaccination but that other girls might [34]. We found a similar opinion concerning anticipated risk behaviour and condom use. Nearly all girls reported that they would not reduce condom use after HPV vaccination (only 1% for both groups), but 17% (vaccinated) and 26% (unvaccinated) thought other girls would.

There were no significant differences amongst vaccinated and unvaccinated girls for reported condom use with a casual or steady partner. However, sexually active vaccinated girls were more aware of the risk of HPV infection when engaging in unprotected sex. Irrespective of vaccination status, only a quarter of the girls reported to always use condoms with a casual partner and 18% with a steady partner. In line with Mather T et al. [35] inconsistent or no condom use was reported by 50% of the girls with a casual partner. Although most of the girls (65%) in our study reported using other contraceptive methods, the risk of acquiring HPV or another STI through unprotected sex seems to be high in this population. Therefore, early HPV vaccination of 12-year-old girls will considerably decrease the risk of HPV infection at a later and more sexually active age.

With regard to other sexual risk factors we found that among the vaccinated sexually active girls, a somewhat lower mean number of lifetime sexual partners was reported. However, no differences were found for other sexual behavioural characteristics such as age of sexual debut and history of STIs. These results imply that girls who decided not to get vaccinated were not the ones with increased (sexual) risk behaviour. Thus in contrast to screening, where it has been found that more than half of the cervical cancer cases were found in women who did not attend screening, it seems that although these girls are not benefiting from vaccination, they have no disproportional disadvantage compared to vaccinated girls.

This study has several strengths. Firstly, it was a randomly selected, large, nationwide population-based study. Secondly, vaccination status was derived from a national vaccination database instead of being self-reported. Thirdly, we obtained information on the actual vaccination uptake instead of the intention to vaccinate.

Although a limitation of this study was a relatively low response rate (15%), online surveys/questionnaires, while advantageous, are known for their average lower response rate compared to mail or telephone surveys [36, 37]. Similar or lower response rates were obtained in other studies directed to parents of girls targeted for HPV catch-up vaccination (16%-24%) [38] or to participants recruited from Praeventis (7%) [39]. The response was higher amongst vaccinated than unvaccinated girls (19% vs. 11%) similar to other studies [38]. In order to assess the effect of this response rate we determined if the characteristics of the study population were similar to those of girls in the general population, by comparing our data on education, ethnicity and age of sexual debut. Girls in our study were comparable with respect to sexual debut with another Dutch study [40] but were slightly higher educated than the general Dutch population (59% vs. 47%), and were more often not Dutch (4.7% vs. 3.3%) [41]. Nevertheless, our sample size was adequate for the proposed statistical analysis of association with vaccine uptake and the possible influence of differences in ethnicity and education were controlled for in the multivariable analysis. Finally, although we have no indications that our results are not applicable to 12-year old girls that are targeted in the routine HPV vaccination program, we cannot rule out that this might be somewhat different. That is, the decision-process towards vaccine uptake may be more influenced by parents/caregivers in this younger age group.

Routine HPV vaccination in the Netherlands has the potential to reduce the inequity of prevention of cervical cancer. In particular, vaccination uptake was not associated with factors that are known to be associated with non-attendance in the cervical cancer screening program, such as education and ethnicity. Furthermore, most sexual characteristics were comparable amongst both groups indicating that unvaccinated girls are probably not at higher risk of exposure to HPV compared to vaccinated girls. Although in general knowledge could be improved, the large majority of participants knew HPV caused cervical cancer suggesting an informed vaccination choice was made.

Madelief Mollers and Karin Lubbers shared first authorship.