Introduction

The human papilloma virus (HPV) and the HPV infection should by no means be considered as a problem of the past decades. The first reports about the HPV virus and the effects of the HPV infection have come from antiquity. HPV infection is the most common sexually transmitted disease nowadays and is the main cause of cervical cancer. Up to now, more than 100 subtypes of HPV have been identified [1]. Although most HPV infections are asymptomatic and regress spontaneously within a few years [2], it is estimated that the prevalence of genital infection from any type of HPV during 2011–2014, concern the 42.5% of adults aged 18 to 69 in the USA [3].

The types of HPV according to the risk of oncogenesis are distinguished at high and low risk. Low-risk types are detected in exorbent warts, warts, and low-grade cervical intraepithelial lesions. High-risk HPV genotypes accompany high-grade intraepithelial lesions, mainly of squamous cervical epithelium and invasive cancers [4]. Persistent infection by certain types of HPV can cause cancer and genital warts. The HPV genotypes 16 and 18 are responsible for about the 66% of cervical cancers [5], 25% of high-grade intraepithelial cervical lesions, and 50% of cervical malformations [6]. HPV types 6 and 11 are estimated to be responsible for about 90% of genital warts [7].

The comprehension of the causal relationship between the HPV infection and cervical cancer has led the scientific community of the USA, to the discovery of the first HPV vaccine that changed completely the scientific data on the primary prevention of the cervical cancer nowadays. The first vaccine (Gardasil) was released in 2006, and it was effective against four HPV genotypes, while 1 year later, the bivalent vaccine (Cervarix) was approved for distribution. In 2014, the nine-volume vaccine against HPV (Gardasil 9) was released. Indisputably, in the course of the vaccination research, many problems and controversies have arisen with regard to the disposal of vaccines (manufacturing costs, cross-prophylaxis, cost-effectiveness). Nevertheless, it is commonly accepted that vaccination against HPV leads a very important health issue close to its effective treatment [8]. Vaccination changes the natural history of the disease at an early stage, affecting not only the progression of malignancy but also the precancerous stages as well [9, 10].

Methodology

The method used in the research case of our study is the systematic review of the literature. The systematic bibliographic review aims to identify, assess, and select properly designed research studies, in accordance with predetermined and clear scientific criteria. After defining the research question and searching for relevant studies within the international literature consequently, the criteria for the inclusion and exclusion of the studies, the flow diagram of the search and selection process, the summary table of the selected studies and the quality assessment of those, form in each case steps decisive, and of paramount importance for the successful accomplishment of the systematic bibliographic review. A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines–based approach was used to query PubMed from 2010 until 2019 (22). Medical Subjects Headings (MeSH) and non-MeSH terms were applied broadly with filters, implementing key words, such as HPV OR human papilloma virus OR human papilloma viral infection); epidemiology study OR descriptive study; attitude adolescence or adultescence; vaccine OR vaccination or OR vaccination program or implementation of vaccination program OR attitude towards vaccine OR immunization OR coverage; education OR training OR education OR education education OR education initiatives OR school initiatives OR school intervention/prevention school–based OR intervention facilitate school intervention; AND (acceptance of behavior or OR attitude to health OR increase vaccination coverage), with all possible combinations, as it is described in the table below (Table 1). The reference lists of previously published reviews were also examined to identify additional potentially relevant studies.

Table 1 Key words for the systematic search for studies investigating the relationship between HPV and adolescent HPV vaccination and the role of their training in the acceptance of HPV vaccination in the Medline/PubMed database
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The search of the literature will also be carried out through additional recordings relevant to the subject under investigation, resulting from the search of other data sources, such as communication with specialized health scientists, conference proceedings, and doctoral theses.

Prespecified inclusion and exclusion criteria are listed as follows:

  1. 1.

    Publication language: Studies published in English.

  2. 2.

    Publication date: Surveys published after 2010.

  3. 3.

    Study content: Surveys analyzing the relationship between the study of the recording of adolescents’ knowledge on HPV and HPV vaccination and the role of their training in the acceptance of vaccination against HPV.

  4. 4.

    Type of study: Synchronous studies, cohort studies, observational studies and quantitative studies published in scientific journals, conducted internationally, will be included. Only studies with access to the full article will be included.

  5. 5.

    Study sample: The sample size of the studies included should be ≥ 50, consisting of both boys and girls, aged between 13 and 20 years. Participants should respond to the questionnaires or interviews themselves.

  6. 6.

    Report: Participants in the included studies should respond themselves to the questionnaires or interviews. Participants should have received even one dose of the HPV vaccine, or express a willingness to be vaccinated. Studies in which the questionnaires were answered by parents or guardians, doctors, and teachers will be excluded.

  7. 7.

    Outcome: Studies proving the relationship (or the lack of it) between education and positive perception of the HPV vaccination will be included in the review. Ideally, studies that will determine the influence factors and best educational interventions, in order to raise awareness on the HPV vaccination, will be included as well.

  8. 8.

    Studies from the most prestigious scientific journals of medical science will be included and all judged.

  9. 9.

    Studies with a date of publication before 2010 will be excluded.

Flow Chart

The depiction of the results of the research strategy will be accomplished using the following flowchart (diagram 1), which summarizes the search and selection process.

Diagram 1
figure 1

Flow diagram of the search and selection process of the studies included in the systematic literature review [11]

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Data for the points of interest were extracted from the text of included studies whenever possible. When a study met inclusion criteria but required outcome data were not obtainable, the article was excluded from the analysis.

Selection and Presentation of Studies

The following table (Table 2) presents the articles and studies found according to the relevant topic search, as described in the methodology.

Table 2 A summary of the studies selected to be included in the systematic review
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Grading Studies

Studies meeting the inclusion criteria and accepted for evaluation were assigned for clarity, completeness, and quality of non-randomized studies to be used in a systematic review. The evaluation of the studies was carried out using the quality assessment scale for witness/patient cohort studies, as defined by the “Newcastle – Ottawa Quality Assessment Scale Case Control Studies.”

This scale evaluates 8 elements and uses a star system with a maximum of 9 stars, in order to evaluate non-randomized studies using 3 criteria: choice of patients or study groups (4 stars), comparability of study groups (2 stars), and its ascertainment of the report or outcome of interest, in the case of control or cohort studies respectively (3 stars). Studies achieving a score of 6 stars or more are considered to be of good quality. Grading of the studies was performed by 2 authors (IT, GL), and presented in consensus fashion to the entire group. The final step in this systematic review is the assessment of the studies that have been included, as indicated in the tables below (Table 3 and Table 4).

Table 3 Table of assessment of the quality of cohort studies based on the Newcastle–Ottawa rating scale
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Table 4 Table of assessment of the quality of patient–witness studies based on the Newcastle–Ottawa rating scale
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Results

The systematic review questions produced 70 articles. Eleven studies were identified that met the inclusion and exclusion criteria. Seven studies were high rated on the Newcastle–Ottawa rating scale and 4 were rated as moderated. The results of the studies will be discussed here and concluded that a proportion of adolescents aged 13 to 18 years old and adults up to the age of 20, seem to be unaware of the HPV infection and the effectiveness of the HPV vaccines. The success of HPV vaccination programs will require awareness regarding HPV associated diseases and the benefits of HPV vaccination.

This study yielded two major themes. First is the knowledge of HPV infection and the perception whether there is a correlation between the HPV infection and cervical cancer. A small percentage (25%) is estimated to have heard about the HPV and the prophylactic vaccination, whereas only one-third of the participants (33%) found to have been informed about the association between HPV and cervical cancer [12,13,14,15,16,17,18]. In some studies, depicted that the adolescent participants had a good knowledge on the HPV infection while in others the frequency was very poor with a range between 15 and 80% [12,13,14,15,16,17,18]. However, the awareness was much higher in females, especially the ones belonging to urban setup compared to boys, (45–50% vs. 15–26%) respectively [19, 20]. Only 7 to 32.3% were aware that HPV causes cancer in the uterine cervix [12,13,14]. The most important factors related with the level of awareness of HPV infection and its implications were gender, socio-economic status, education, sexual habit, family history, and whether vaccination against HPV was include in the national vaccination scheme.

The second issue was the adolescence perception about the importance of prophylactic vaccines against HPV infection and the willingness to be vaccinated. The study identified a significant gap in knowledge on cervical cancer prevention could be performed through vaccination scheme. The range between the studies varied from 25.1 to 95% that had heard of HPV vaccine [14, 17, 20, 21]. The difference between intention to be vaccinated and starting vaccination was considerable large. Among women, a percentage ranged from 11.6 to 100% would plan to undergo vaccination against HPV [12,13,14,15,16, 19, 21], while men intended to vaccinate in a smaller percentage between 10.1 and 40% [1, 19]. A small portion, 4.7%, of women aged 16–26 reported that did not wish to be vaccinated and 16.3% were indecisive [21]. The uptake of HPV vaccination rates was ranged from 0.4 to 67% among the studies [6, 12, 13, 16, 18, 21, 22]. The most important factors leading to the aforementioned rejection were the uncertainty or ignorance of the benefit and utility of vaccination after the onset of sexual activity are the origin, sexual behavior, education, morals, experts’ views, role of the media, the cost of vaccine, and the inclusion or not to national vaccination program. However, the picture seems to change after the treatment and explanation of the vaccine-related barriers.

Discussion

This study presents two major themes. Nowadays, both teenagers and parents are poorly informed on issues of HPV infection and its implications. Secondly, the low tendency of vaccination against the cervical cancer is explained by the underestimation of the likelihood of infection by the virus. Factors presented barriers against or contributed towards to gain knowledge regarding the HPV infection will be analyzed thoroughly.

Which Factors Were Related to Knowledge of HPV Infection?

Gender

The results of this systematic review indicate that the majority of participants who were aware of the effects of HPV, the existence of HPV vaccines, and the benefits of vaccination were women [12,13,14,15, 19, 20]. Durusoy and his colleagues attribute this to the fact that awareness raising campaigns are addressed mainly to girls and women and less to boys and men [12]. Thus, with regard to the relationship between gender and the depth of knowledge about HPV infection and its preventive vaccination, it is estimated that in most research studies, girls had a better awareness of this issue than boys. The above statement shows the need to educate men further in order to change their perception about the risk from HPV virus. However, Gutierrez and his colleagues, analyzing the results of their studies, indicated that homosexual teenagers are much more updated on HPV transmission, than heterosexual men. This was attributed to the fact that HPV is also associated with the development of rectal cancer. This has been attributed to the fact that homosexual participants have more experience in the care of their sexual health, such as prophylactic HIV care, in comparison to the heterosexual men [17].

Socio-economic Status

The socio-economic status of the participants is also a determining factor concerning the level of information, the attitudes and the receptiveness of respondents about the HPV and vaccination. Participants with a high socio-economic status had better results in their responses and were more willing to vaccinate, or receptive to prophylactic vaccination than those who belonged to the lower and economically weaker social classes [12, 21]. Mortensen and associates in their review in 2010 indicated that the acceptance of vaccination is related to the level of education and the socio-economic status of the parents, without being able to accurately determine which of the two factors are the most important [22].

Educational Level

Furthermore, parents’ educational attitudes are slightly more significant factor than the socio-economic level, with regard to HPV virus and its implications. Two studies concluded that there is a proportional relationship between the level of education and the demonstrated knowledge, with people of higher education having a substantial level of knowledge about HPV [14, 21]. On the other hand, in 2011, Blodt and colleagues analyzed the results of their own study to show that women with migrant background, as well as the less-educated ones, have lower rates of receptiveness of HPV vaccines, and that than those of a higher educational level [20].

Sexual Habit

Furthermore, the sexual habit is another determining factor contributing to raising the awareness of participants in research studies. Sexually active respondents demonstrated better scores in questions about HPV infection, in comparison to women who were sexually inactive [12]. At the same time, Rama and colleagues found that the previous infection with a sexually transmitted disease had a positive influence on both the level of information and the intention of undergoing a prophylactic HPV vaccination [14]. The same conclusion was reached by a most recent study which indicated that sexually active teenagers, especially girls who only had vaginal intercourse, are more likely to have a higher level of knowledge about the HPV infection and were more likely to adopt a positive attitude towards the possibility of vaccination against the virus [15].

Family History

Moreover, another determinant of the level of awareness and knowledge about the HPV infection and its preventive vaccination is the existence of a family history of genital cancer. The study by Durusoy and his associates in 2010 concluded that girls with a family history of genetic cancer have a 2.3-fold higher chance of having heard about HPV vaccination [12].

Cost of the Vaccine

Finally, a very important factor that increased the knowledge of HPV virus was the inclusion of vaccines against HPV in the national vaccination program of the countries and when this type of vaccination was delivered without any financial obligation [12].

The second issue that needs to be addressed is that both teenagers and parents are poorly informed on HPV preventive vaccination program. However, the picture seems to change after the explanation of the vaccine-related benefits. Mortensen and his colleagues in their study which included 435 women from Denmark aged 16–26, found that most of the participants were up-to-date on vaccination against cervical cancer and only about 20% of them had not yet decided whether to undergo HPV vaccination or not. Of the women who had expressed their intention on HPV vaccination, only half of them eventually accepted [22]. The fact that previous studies that had been included in the systematic review, depicted a very high HPV vaccination acceptance rate internationally, suggests that the difference between intention and action may be significant. Moreover, the data from the studies indicated that the overall awareness of HPV vaccination is equally low, among both rural, and urban residents [13].We analyzed the factors that contributed to unwillingness for vaccination.

Sexual Behavior

In this review, it is revealed that there is a wide range of behavioral approaches, with regard to the intention to vaccinate against HPV from country to country, with Western countries having higher vaccination rates (75– 80%) than the Eastern ones (48–63%). It is very important to address that it was notice great difference in the level of knowledge and awareness about HPV infection and HPV vaccination, among teenagers according to their sexual behaviors. Men who have sex with individuals of the same gender, were more likely to enroll to an HPV prophylactic vaccination program than the heterosexual ones [17].

Educational Level

An important stimulating factor towards the promotion of the HPV vaccination is also demonstrated by the attitudes of girls’ parents, especially those aged 11 to 18. Studies have proposed that parental knowledge, parental counseling, and financial support are very important factors for the acceptance of the HPV vaccination by adolescents of both sexes [13, 16, 22]. In particular, aware mothers are thought to have a great potential to persuade their daughters, in order to take active measures for the primary prevention of cervical cancer [19]. The same conclusion seems to be drawn for boys on their intention on completion the HPV vaccination program, as their mothers seem to have a significant influence on their decision to vaccinate against HPV [17]. While in another study was concluded that neither parental nor teenage knowledge was related to the future vaccination tendency of adolescents. In particular, it is reported that some participants with low informational status about the HPV and its preventive vaccination, eventually ended up integrating into and completing the HPV vaccination program, while people who at first demonstrated a high level of knowledge, were not vaccinated against HPV. This suggests that for many of the participants, information was neither necessary nor sufficient for a final positive decision [18].

Morals

Additionally, the attitude towards the vaccination intention in relation to the fact that HPV is a sexually transmitted virus, depends to a large extent on the current sexual morals and moral barriers that prevail in society. In the Mortensen study in 2010, it is mentioned that both men and women, after comprehending the sexual transmission of HPV, have expressed greater interest and willingness, to undergo the preventing vaccination against the HPV infection [22]. Hussain and his colleagues, in 2014, found that Muslim religious participants demonstrated lower levels of knowledge about the HPV infection and HPV vaccination, than those of the Hindu religion. This has been attributed to the low prevalence rates of HPV among Muslims, in which sexual behavior rules are clearly stricter for girls [13].

Expert’s Views

Furthermore, the contribution of physicians in the information of the young women is another factor in forming a positive opinion on HPV vaccination [16]. Mortensen in 2010 and Blodt 1 year later concluded that while in most countries’ HPV, vaccination is now part of the national vaccination program, doctors generally overlook to inform youngsters about the HPV vaccination, but when they do, they positively influence their intention to undergo a vaccination [20, 22]. Durusoy’s and Gutierrez’s studies revealed in particular that participants who regularly attended a gynecologist had better information on the HPV and the effects of HPV infection, demonstrating higher rates of intention to undergo vaccination and participation in an HPV vaccine program [12, 17].

Role of Media

Furthermore, the importance of the role of the media and social media has been studied and evaluated by numerous research studies. In the study of Durusoy and his associates in 2010, as well as in the later study of Lee’s research team in 2014, newspapers, magazines, television, and social media were the primary source of information about this issue [12, 16]. Bearing in mind the above mentioned outcomes, it should be noted that the way the issue is presented through media and social networking, as well as the validity of the information provided, plays a decisive role, since, according to the Mortensen survey, women whose main source of information was the media, tended to believe that HPV vaccination did not concern them, nor did they have enough benefits, resulting frequently in non-acceptance of HPV vaccines [14, 22].

Cost of Vaccine Against the HPV

Additionally, the total or partial financial coverage of the vaccine’s cost by national institutions, appears to be a positive influence factor in increasing the level of HPV vaccination [12, 22]. More specifically, Mortensen in 2010 concluded that women were more likely not to be vaccinated, as well as refusing any information about HPV and prophylactic vaccination, in those cases where they had to pay for the cost of the vaccines. From the results of the qualitative study conducted, it is revealed that the lack of information was a less important inhibitor factor, when vaccination was free of charge, whereas in cases where women had to pay for the vaccines, the lack of knowledge became a decisive inhibitor factor [22].

Vaccination Program

Finally, a very interesting result from the research of Blodt and Napolitano is that the integration and completion of a preventive national vaccination program is not necessarily commensurate with the level of knowledge of vaccinated individuals. In particular, their studies indicated that women who were vaccinated against HPV, had an equal informational status about the virus as the non-vaccinated ones, although it would have been self-evident that the vaccinated women and men, had probably received at least the basic information about the virus and HPV vaccination [12, 15, 17, 20, 22].

Restrictions of the Study

This review is subject to certain limitations. It has to be mentioned that there are studies from research teams in a language other than English, so the published material may be underrepresented. It is likely that some studies would explore adolescent’s knowledge about the HPV virus, but they probably not include the other key words and/or have not taken into account because they did not meet all the criteria. The author estimates that the design followed in this review, has documented the available literature.

Conclusions

The integration of HPV education at the secondary educational curriculum could be considered for those countries that do not have yet implemented a relevant program. The common positive influence factors observed in both sexes were the outset of the sexual life and the overall informational level on the HPV and HPV vaccination. The possible inclusion of a specially formulated chapter on sexually transmitted diseases, in the high school curriculum of the general biology course, could be an important educational tool to raise awareness among school-aged adolescents.

In addition, the type of the informational campaign implemented could be a significant influence factor. Scientifically documented campaigns published in magazines, or television programs targeting to teenage groups and young adults, are estimated to be more effective than those presented in other media. Moreover, awareness raising campaigns through social networking seem to have a higher impact on the individuals than those including brochures and imprints. Also, among the conclusions of this systematic review, it is highlighted that public health campaigns concerning HPV and its vaccination, targeted to men in order to enhance their interest in the preventive health care, are fully justified. However, a better understanding of how to increase individuals’ intentions is needed.

Finally, the results indicate that the HPV prevention policy worldwide is currently centered on cervical cancer prevention, rather than on full acknowledgment on the nature of sexually transmitted diseases. The role of healthcare providers is also of high importance, since the free distribution of the vaccine was a determining factor in the vaccination intention. HPV training should be expanded so that adolescents and young adults should be able to take informed and responsible decisions about their health behavior, including how they will be sexually active, regardless of their choice of receiving or not immunization.