Facilitators and barriers HPV unvaccinated girls after 5 years of program implementation

Abstract

Understanding perceptions and characteristics of human papillomavirus (HPV) vaccinated and non-vaccinated girls can inform communication activities and vaccine delivery strategies. The purpose of this study was to evaluate knowledge and factors associated with HPV unvaccinated girls after five years of vaccination program implementation in Sicily, an Italian region with low vaccination coverage (<50.0%).

A cross-sectional study was conducted through a questionnaire designed to assess knowledge and vaccination status of girls of 1997, 1998, 1999, and 2000 birth cohorts. The sample consisted of 350 girls who attended three high schools. Multivariable logistic regression analysis was conducted to examine predictors of vaccine refusal.

The survey sample of girls shows that the 43.1% were HPV unvaccinated. A significant increased risk of being unvaccinated originated from the belief that the vaccine was too new (AdjOR = 21.08, CI_95% = 2.57–172.97) and that it may cause cervical cancer (AdjOR = 4.36, CI_95% = 1.26–15.07), along with having friends as a source of information on the vaccine (AdjOR = 3.67, CI_95% = 1.63–8.25). A significant inverse association was observed between being unvaccinated and having Pediatrician/General practitioner as a source of information on HPV vaccine (AdjOR = 0.40, CI_95% = 0.24–0.68).

Many girls lack the fundamental knowledge about the HPV vaccine. The key issue is the promotion and implementation of information programs to raise awareness of girls on the importance of the vaccine.

Keywords: :

• HPV vaccination barriers
• HPV vaccination knowledge
• HPV infection knowledge
• friends as source of information
• Pediatrician/General Practitioner as source of information
• HPV vaccine efficacy
• HPV vaccine security

Introduction

Carcinoma of the cervix is the second highest in the world among cancers in women. The etiological factor of this cancer is a pool of high-risk strains of the human papilloma virus (HPV), which are transmitted through sexual contact. Carcinogenesis is a long lasting process, in which cancer represents the final stage of evolution of a series of at risk lesions progressively higher, which, particularly at the initial stage, may spontaneously regress.¹ In Italy there are just over 53,000 women with a diagnosis of cervical cancer, and it is estimated that to experience a death due to cancer of the cervix, it is necessary to follow 1087 women for a lifetime.² Prevention strategies have made it possible to identify the 8% of this burden in less than two years after diagnosis, 14% between 5 and 10 y and 44% over 20 y.

Vaccination is the most effective method of primary prevention of cervical cancer. In Italy HPV vaccination is offered free of charge and actively to the children in the twelfth year of life from 1997 birth cohort.³ Some Italian regions have extended vaccination active offer to other age groups and they provide subsidized payment for age groups not being active call. Five years after the start of the immunization program against HPV and the dissemination of information campaigns, vaccination coverage for three doses of HPV vaccine appears to be stabilized at around 69%, without showing the expected increase in new invited cohorts. A large variability continues to be evident between regional data. Sicily is one of the regions with the lowest immunization coverage against HPV, as being the immunization coverage for three doses of HPV vaccine in the 1997, 1998, and 1999 birth cohort only 55.3%, 54.3%, and 56.0%, respectively.⁴

Barriers to vaccine adoption are multi-factorials. Understanding the perceptions and characteristics of vaccination acceptance can inform communication activities and vaccine delivery strategies.⁵ Previous studies indicate poor knowledge about HPV infection and vaccine in the general population but also in target groups.^6,7 Several studies have shown that vaccinated and unvaccinated girls have similar levels of knowledge about HPV and HPV vaccine.^8,9 Some studies have evaluated HPV knowledge in young females before that HPV vaccine was introduced. However, it is also important to assess the knowledge of girls after vaccination programs have been implemented, particularly considering that also in vaccinated cohorts of girls, the route of transmission of HPV infection and the link between HPV and cervical cancer are scarcely known.^10-12

A few Italian studies on girls under 18 y old explored the characteristics of HPV vaccinated only. One study performed on young women who underwent HPV vaccination in Local Health Units (LHU) and on women who attended University in the same city showed that under-18’s were mostly informed by General Practitioners (22.6%), pediatricians (15.4%) and healthcare workers of LHU (13.3%).¹³ Another study conducted in northern Italy three years after the beginning of HPV vaccination programs showed that, despite a broad information campaign on HPV related diseases and vaccination, routes of transmission knowledge within the vaccine eligible girls was still limited (74.6%).¹⁴ Little is known about the barriers encountered by adolescent girls against the HPV vaccine.

The purpose of this study was to evaluate factors associated with HPV vaccination refusal in Sicily, south Italy, after five years of vaccination program implementation and dissemination of information campaigns, in order to identify knowledge gaps and possible targets of educational interventions.

Material and Methods

A cross-sectional study was conducted through a questionnaire designed to assess knowledge and vaccination status about HPV of the Sicilian girls of 1997, 1998, 1999, and 2000 birth cohorts. The sample consisted of girls who attended three high schools in Palermo area, in which directors and teaching boards gave their consent to the study. This area has a population of 1 243 638 inhabitants and includes a total of 19 606 girls attending high schools in the birth cohorts under investigation.¹⁵ Participating high school where selected to be as representative as possible of the different Palermo geographical area relatively to knowledge, attitudes and behaviors toward screening and vaccination against HPV and reliable source of information. The survey was administered in April 2013 and questionnaire was managed by the working group in a single day for each school. The questionnaire was given to students as class work and filled in by all girls present on that day. Prior to administration of the questionnaire the working group explained, the purpose and the method by which the survey was conducted. Students had about ten minutes to complete the questionnaire anonymously, without any specific assistance.

The questionnaire was divided into three main sections: the first was related to demographic characteristics of the girls (i.e., age and number of family members), vaccination status (unvaccinated: no injection received; vaccinated: at least one of three-shots of HPV vaccine series received) and HPV infection knowledge; the second regarded the knowledge on HPV vaccine; the third evaluated girl’s sources of information on HPV vaccine.

Descriptive analysis were used to characterize the study sample and detect differences between unvaccinated and vaccinated girls. For categorical variables, absolute and relative frequencies were computed; continuous variables not normally distributed were represented as median (interquartile range, IQR). Differences between groups of continuous variables with normal distributions were examined using an unpaired T-test; for continuous variables non normally distributed Wilcoxon-Mann-Whitney test on the equality of medians was applied. The normal distribution was assessed with Shapiro-Wilk test. Categorical variables were compared using X² test. The odds ratio (OR) and corresponding 95% confidence interval (CI_95%) was also calculated. The level of significance chosen for all analyses was 0.05 two-tailed test. Also, bivariable associations between being unvaccinated and the characteristics in analysis were conducted; variables founded to be significantly associated were included in a multivariable model. The goodness of the fit was calculated for each model, and the model with the lowest log-likelihood ratio test was considered as having the best predictive ability. All analyses were weighted to adjust for differential participation and differential non response by using the software Stata/MP 11.2.

Results

A total of 378 girls of birth cohort from 1997 to 2001 participated in the survey. Twenty-eight girls (7.4%) were unsure of their cervical cancer vaccination status and thus were not included in the analysis.

Altogether, the study cohort consisted of 350 adolescents (Table 1), most of which (96.3%) knew that HPV was a sexually transmitted infection and that it was associated to cervical cancer (83.4%), while only a few (12.3%) knew that it causes genital warts. About 70% of the girls knew that HPV vaccine alone did not guarantee for safe sex. Only a few girls (5.7%) had obtained their information on the HPV vaccine from the school, while almost half had their mother as a source of information.

Table 1. Demographic characteristics and HPV knowledge in the study cohort

Variable	Total (n = 350)	Unvaccinated girls (n = 151)	Vaccinated girls (n = 199)	p ^a
Age [year, mean (CI 95%)]	14.8 (14.7–14.9)	14.9 (14.7–15.0)	14.8 (14.7–14.9)	0.486
Family members [n, median (IQR)]	4 (4–5)	4 (4–5)	4 (4–4)	0.519
HPV infection knowledge n (%)
HPV infection is sexually transmitted	337 (96.3)	141 (93.4)	196 (98.4)	0.002
HPV infection cause genital warts	43 (12.3)	22 (14.6)	21 (10.5)	0.259
HPV infection cause cervical cancer	292 (83.4)	117 (77.5)	175 (87.9)	0.006
HPV infection cause bladder cancer	28 (8.0)	11 (7.3)	17 (8.5)	0.664
HPV infection cause cystitis	20 (5.7)	8 (5.3)	12 (6.0)	0.767
HPV infection cause other diseases	44 (12.6)	28 (18.5)	16 (8.0)	0.003
HPV vaccine knowledge n (%).
The vaccine protects against all sexually transmitted diseases and allows to have safe sex	107 (30.6)	49 (32.4)	58 (29.1)	0.473
The vaccine protects against sexually transmitted diseases, but it is necessary to adopt methods of prevention during sexual intercourse	244 (69.7)	102 (67.5)	142 (71.3)	0.510
The vaccine is effective	114 (32.6)	32 (21.2)	82 (41.1)	< 0.001
The vaccine is safe	96 (27.4)	38 (25.2)	58 (29.0)	0.435
The vaccine can cause cancer	14 (4.0)	10 (6.6)	4 (2.0)	0.028
The vaccine is too new	14 (4.0)	13 (8.6)	1 (0.5)	< 0.001
Source of information on HPV vaccine n (%)^b
Pediatrician/General Practitioner	112 (32.0)	32 (21.1)	80 (40.2)	< 0.001
Gynecologist	21 (6.0)	7 (4.6)	14 (7.0)	0.359
Vaccination center	21 (6.0)	5 (3.3)	16 (8.0)	0.068
School	20 (5.7)	12 (7.9)	8 (4.0)	0.112
Friends	36 (10.3)	26 (17.2)	10 (5.0)	< 0.001
Mother	181 (51.7)	74 (49.0)	107 (53.8)	0.419
Other family members	23 (6.6)	11 (7.3)	12 (6.0)	0.624
Newspapers/magazines	11 (3.1)	9 (5.9)	2 (1.0)	0.008
TV/Radio	23 (6.6)	14 (9.3)	9 (4.5)	0.072
Websites	2 (0.6)	2 (1.3)	0 (0.0)	0.102
Other	18 (5.1)	10 (6.6)	8 (4.0)	0.267

^a Significant values in bold; ^bRespondents were free to select more than one source (column totals greater than 100%).

A total of 151 girls (43.1%) reported to be unvaccinated against HPV infection. A lower percentage of unvaccinated compared with vaccinated girls was aware that HPV infection was sexually transmitted (93.4% vs. 98.4%, P = 0.002) and knew that HPV infection was associated to cervical cancer (77.5% vs. 87.9%, P = 0.006). While knowledge of the association of HPV with cervical cancer was similarly in the two groups, a higher rate of unvaccinated girls believed that HPV infection was associated to diseases other than those listed in table, compared with vaccinated girls (18.5% vs. 8.0%, P = 0.003). A lower rate of unvaccinated girls thought that the HPV vaccine was effective, compared with vaccinated girls (21.2% vs. 41.2%, P < 0.001); on the other hand, more unvaccinated girls believed that HPV vaccine caused cervical cancer (6.6% vs. 2.0%, P = 0.028) and that it was too new (8.6% vs. 0.5%, P < 0.001). As far as information on the HPV vaccine was regarded, a lower rate of unvaccinated girls had the Pediatrician/General Practitioner as a source of information, compared with vaccinated girls (21.1% vs. 40.2%, P < 0.001); in contrast, more unvaccinated girls had friends and newspapers/magazines as an informative source of HPV vaccination, compared with those vaccinated (17.2% vs. 5.0%, P < 0.001 and 5.9% vs. 1.0%, P = 0.008, respectively).

Table 2 shows results from multivariable logistic regression analysis, performed by taking into account the variables found to be significant in the bivariable analysis. Factors that were confirmed as significant risk for being unvaccinated against HPV were the belief that HPV vaccine was too new (AdjOR = 21.08, CI_95%: 2.57–172.97) and that it may cause cervical cancer (AdjOR = 4.36, CI_95%: 1.26–15.07), along with having friends as a source of information on HPV vaccine (AdjOR = 3.67, CI_95%: 1.63–8.25). A significant reduction of risk to be unvaccinated was observed when Pediatrician/General Practitioner was the source of information on the vaccine (AdjOR = 0.40, CI_95%:0.24–0.68).

Table 2. Multivariable logistic regression of factors associated with vaccine refusal

	AdjOR	CI 95%
HPV vaccine is too new (yes vs. no)	21.08	2.57–172.97
HPV vaccine can cause cervical cancer (yes vs. no)	4.36	1.26–15.07
Friends as source of information on HPV vaccine (yes vs. no)	3.67	1.63–8.25
Pediatrician/General practitioner as source of information on HPV vaccine (yes vs. no)	0.40	0.24–0.68

Discussion

This study was designed to integrate public health data on HPV vaccine status and vaccine acceptance, in girls who had been trained on HPV vaccination and in the age range eligible to the first dose of HPV vaccine.

Altogether, adolescents were found to have a good degree of knowledge on HPV infection, sexual transmission and association to cervical cancer, even though only a few girls knew that the infection frequently causes genital warts. This finding is in accordance with what has been showed in previous studies performed in USA on high school and college age women.^8,9

The 56.9% vaccination coverage founded in this study is in line with that reported by the Italian National Health Services in 2013, where 62.1% of adolescents from 1997 to 2000 birth cohorts had received one dose of vaccine.² The 56.9% rate is far from the national target of at least 95% for HPV vaccination coverage 5 y after the implementation of HPV vaccination. In the light of the good level of knowledge on HPV infection evident in the study group, a likely explanation for 43.1% of the girls being unvaccinated are concerns regarding the vaccine, its effectiveness, safety and acceptability. Indeed, the risk of being unvaccinated was associated to the belief that the vaccine was too new (AdjOR = 21.08) and could cause cervical cancer (AdjOR = 4.36). These reasons for vaccine refusal differ from findings in a previous study, performed in California on adolescent girls, which reported a perceived 7% lack of safety of the vaccine.¹⁶ On the other hand, a study on college-aged women found that unvaccinated subjects were less informed on HPV infection compared with those vaccinated (median knowledge score 58.3 vs. 66.7, respectively) and also had more concerns about the vaccine’s safety (median perceived barriers: 0.5 vs. −1.0, respectively).¹⁷ These results highlight the importance of providing adequate information on the vaccine's safety and efficacy, with attention also that should be paid that such information is clearly understood.

Another finding from this study was that having friends as a source of information on HPV was associated to an about 4 times increased risk for vaccine refusal. Not surprisingly, as being HPV infection related to sexuality, it has been reported that the confidential aspect induced young girls to treat the topic with their peers, rather than with parents or caregivers.¹⁸ Not unexpectedly and as also previously showed, such a behavior can cause a distortion of the information, as being the latter provided by persons not adequately prepared and/or appointed to the task.⁹ Of note, this finding is an issue also in the light of the fact that, in the present analysis, the school was a source of information only in 5.7% of the total cohort of girls examined. It has been showed that the rate of acceptance of the vaccine is considerably lower (19–71%) in the lack of school-based programs than in the presence of the programs (65–86%).¹⁹ Thus, to achieve a higher uptake of the vaccine, it could be offered in the context of school-based voluntary vaccination and information campaigns, as already implemented in other countries.²⁰

In agreement with the previous findings from this analysis, a decreased risk of being unvaccinated was associated to having a Pediatrician/General Practitioner as a source of information on the vaccine (AdjOR = 0.40). Evidence has been provided that high school girls, in their decision-making process on the HPV vaccination, have confidence in the information provided by nurses and physicians.²⁰ Also, when provided with adequate and clear information, most of 14–17 y old girls are capable to make decisions about their own health care as competently as adults.²¹ Altogether, these findings suggest that programs aimed to increasing vaccination coverage should also involve either Pediatricians or General Practitioner, depending on the age of the target.^22,23

A limitation of this study is that information of the vaccine status of the study group was obtained from self-reporting, and this may have introduced some error in estimating of HPV immunization rates. Nevertheless, this potential bias was limited by the exclusion from the survey of the girls who had uncertainty about their vaccination status.

The strengths of the study are mainly two. First, an approach was chosen of a not prepared administration about the questionnaire at school, with a limited time for completion; this allowed to avoid biased responses, as influenced by parents and/or information media (websites, newspapers, books), which would misrepresent the true level of students’ knowledge. Second, by administering the questionnaire during school hours, as a kind of class work, the advantage was that the questionnaires were returned as duly completed by all the girls.

Altogether, the results from this analysis show that the key issue in rising knowledge and awareness of girls on HPV vaccine is the promotion and implementation of adequate and complete information campaigns. Strategic, in that sense, will also be the role played by healthcare professionals (e.g., pediatricians, general practitioners, gynecologists, operators from vaccination centers) in the context of educational campaigns, as well as in “one-on-one” discussions specifically geared toward high school girls. These perspectives should be taken into consideration when achieving a high coverage is the desired effect in vaccinating young girls against sexually transmitted HPV infection.

Abbreviations:
y	=	years
AdjOR	=	Adjusted odds ratio
CI95%	=	95% confidence interval
HPV	=	Human papillomavirus
IQR	=	Interquartile range
LHU	=	Local health units
OR	=	Odds ratio
USA	=	United States of America

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Acknowledgements

The authors thank Dr Annarita Filippi for her contribution in the administration of the questionnaire and Prof Vincenza Capursi and Prof Ornella Giambalvo for their contribution in the execution of the statistical analysis.