Explaining the determinants of Human Papillomavirus Vaccine uptake and Strategies to Increase Its Uptake among young adults in Capital of Iran: a qualitative study CURRENT

The HPV vaccine prevents the most common cancer in women, which is cervical cancer. This study aimed to determine the factors affecting the uptake and non- uptake of HPV vaccine in the young adult in Tehran and strategies to increase their vaccine uptake. This is the first qualitative study with the conventional content analysis approach in this context in Iran in 2018-2019. Participants, with a maximum variation in terms of age, sex, educational level, occupation, income, work experience, marital status, were selected purposefully to take part in a semi-structured interview. The data were recorded and analyzed according to the interview continued until data saturation. MAXQDA software version 10 was used for data management. Results The participants were 20 health professionals and 10 young adults from Tehran. Factors affecting HPV vaccine uptake and non- uptake identified as seven categories, including knowledge, health value, external stimuli, outcome expectations, perceived threat, healthcare services, and Contextual factors. Moreover, the strategies to increase vaccine uptake included Compulsory vaccination, vaccine availability, and implementing the educational process.


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Less it is currently understood about male HPV-attributable cancers. Thirty-HPV-associated cancers eight percent diagnosed in men, with oropharyngeal being the most common [3]. Estimations of prevalence indicate that about 79 million individuals infected with HPV, and approximately 14 million people become infected each year [4].
The human papillomavirus (HPV) vaccine can as a primary prevention tool [5]; vaccination reduces HPV-associated diseases like cervical cancer, vulvar cancer, anal cancer, and genital warts [6]. The vaccine first became widely available in 2006 for females [7], And 2010 for males [8], and vaccination rates have steadily increased since then [9,10]. Currently, the HPV vaccination among young adults (19)(20)(21)(22)(23)(24)(25)(26) years of age) with at least one dose ever is 8% for men 40% for women [11]. And Mortensen et al. identified two major factors influencing vaccination uptake -knowledge and structural incentives: 'When structural barriers are low, as in Italy and the UK, acceptability is high, but knowledge does not necessarily follow. When structural barriers are higher, as in Germany and France, the need for knowledge and reassurance is higher [12].
Studies indicate that the following factors were most likely to be associated with future acceptance of the HPV vaccine perceived risks of the vaccine, perceived effectiveness of the vaccine, perceived barriers (e.g., vaccine costs, concerns that the vaccine would promote adolescent sexual behavior), physicians' recommendations and the opinions of significant others (i.e., subjective norms) [13][14][15][16] Human Papilloma Virus (HPV) knowledge is an essential determinant for vaccine acceptance and uptake [17,18]. Very many studies have measured knowledge or awareness of HPV/HPV vaccination [19,20]. An international review of surveys of young women aged up to 26 years reported poor knowledge and misconceptions about HPV and its vaccine [21].
Moreover, a meta-analysis of studies centering on European adolescents reported a poor perception of basic HPV and HPV vaccine knowledge [22].
Few people in Iran use the HPV vaccine, which is one of the most important causes of the lack of knowledge among the public about the vaccine in Iran and when it is injected [23].
Because the HPV vaccine has only recently introduced worldwide, most studies have focused on determinants of future acceptance of the HPV vaccination. None of the studies investigated the 4 causes of uptake and non-uptake between boys and girls. The purpose of this study was to determine the causes of vaccine uptake and non-uptake among girls and boys aged 18 to 27 years and to determine strategies for increasing vaccine uptake in a low vaccine country.

Study design:
An exploratory qualitative study was conducted using in-person and face-to-face interviews with a health professional and young adult.

The participants and the study setting
The present study included 30 participants, including 20 health professionals in various fields (health education and health promotion, gynecology, infectious diseases, dermatology, urology, reproductive health, social practitioner, psychologist) and ten young adults in the age range of 18-27 by purposeful sampling with maximum variation in age, sex, educational level, occupation, income, work experience, marital status .The health professional inclusion criteria included having experience and knowledge about HPV and informed consent to participate in the study. The inclusion criteria for young adults included knowing HPV, informed consent to participate in the study, and the age range of 18-27. The research environment was hospitals affiliated to Shahid Beheshti University of Medical Sciences.

Data collection
The authorization was received from Shahid Beheshti University of Medical Sciences for 12 hospitals.
By referring to different hospitals and talking to the health professional, they were asked to participate in the interview. Young participants were also asked to be interviewed, either as a patient or companion, and if accepted, they offered the time and place of the interview. The interviews were conducted in a place where was most appropriate for the participants (for example, in the hospital and at the university). No one was present at the interview except the researcher and the participants. Each interview began with the purpose of the study, and the participants voluntarily participated in the study. They were asked to answer demographic questions, and then the interview began. The interview guide is listed below. The interviews were recorded, and each interview 5 generally lasted 30 to 60 min. Data collection continued until further information was obtained, and the study saturated with 29 interviews. The interviews were conducted from May to November in 2019, and each interview was transcribed immediately after that. All interviews were conducted by the main researcher (S.Y).

Interview Guide
A semi-structured interview guide was used. The main question asked from the health professionals was: "What do you think of the barriers and facilitators of uptake and non-uptake of HPV vaccine by young adults?" The main question asked from the young adults was: "Which factors encourage or prohibit you from uptake HPV vaccine?". Follow-up and probe questions were also used, such as: "Can you explain more about it?". Two pilot interviews were conducted before the study began. These interviews were not included in the present study. After pilot interviews, there was no significant change in the interview guide.

Data analysis
Data analysis was performed simultaneously with data collection using Graneheim and Lundman's content analysis approach [24]. This method can reveal the hidden themes and patterns of the study from the content of the data obtained from the participants [25].
Immediately after the interview, the interview was transcribed. The transcripts were read several times to get an overall picture of what was said. The transcripts of the interviews were then entered into the MAXQDA Version 10 software. Subsequently, semantic units consisting of related sentences or paragraphs were identified, and the initial codes were extracted. The codes were merged and categorized according to similarities and differences and named as subcategories at different abstracts levels [19]. Regarding the controversial codes, the researchers argued and agreed.
To establish reliability in this study, the four strategies recommended by Schwandt et al. were used [26], including credibility, confirmability, transferability, dependability. To establish credibility, continuous and prolonged engagement researcher involvement used in the present study. Peer check was conducted through the research team by holding meetings and discussing the data and analysis 6 among the researchers themselves and with the specialists. Furthermore, all interviews were recorded and transcribed into written versions. The interviews were summarized, and the data and codes were analyzed by the member check and their feedback was considered. Confirmability indicates the relationship between the data and the resources used. The observance of this criterion emphasizes that the results of the study are not relevant to the researcher's knowledge [27]. Data Confirmability was performed by the main researcher by reviewing and collecting the ideas of other researchers and obtaining relevant studies documentation. Moreover, the Confirmability or review method was performed by the supervisors. To this end, the interviews, codes, and classes obtained by several experts were studied.
Transferability in this study was performed by providing a comprehensive description of the topic, participants, method of data collection, and analysis. To achieve dependability, detailed, and accurate note-taking was also used to provide details to other researchers to study or develop similar cases.

Ethical considerations
The Ethics Committee approved the study at a meeting of the Faculty of Health and Safety at the Neuroscience Research Center of Shahid Beheshti University of Medical Sciences. Moreover, some cases were observed, including obtaining consent from the participants, anonymity, confidentiality, obtaining permission to record audio interviews, and the right to withdraw when they desired.

Results
In this study, data saturation was obtained after 30 interviews. Finally, the data were categorized into 20 subcategories and seven categories. A total of 20 health professionals in different specialties and nine young adults participated in the study. Their mean age was 2.40 ± 0.224 and 24.86 ± 3.761, respectively. The participants' specifications are presented in Tables 1 and 2.
The Qualitative content analysis led to seven categories, including health value, knowledge, external stimuli, outcome expectations, perceived threat, healthcare services, and Contextual factors ( Table   3).

Health value
This category consists of two subcategories, including taking care of health and taking responsibility 7 for health.
Females uptake the vaccine to maintain their health and that of their partners, while males do not care about their health and uptake the vaccine only to maintain their partner's health.
"Girls uptake the vaccine for their health as well as those around them" (Young participant,27 years old).
The participants believed that males do not usually refer to a physician for their illness, and they believe the disease was unrelated to them.

Outcome expectations
This category consists of two subcategories, including the fear of vaccine side effects, the uncertainty of the vaccine's outcome.
Side effects, such as infertility of girls by vaccine uptake, can be a cause for both young people and parents as well as some physicians not to uptake the vaccine. The participants were not sure of the benefits of the vaccine and feared that they would become ill with the vaccine.
"People's trust in the medical system has diminished, and this can play a role in non-uptake. She says maybe I will become ill with the vaccine" (psychologist, 31 years old)

Perceived threat
This category consists of two subcategories called perceived danger, perceived severity.
The perceived danger is the belief that the young person is likely to get the disease. Most of the participants believed that girls were more at risk of illness than boys. Moreover, a lack of confidence in a future partner and having multiple partners are factors for vaccine uptake. Some of the participants did not consider themselves susceptible to the disease due to a lack of sex.
The boys believed that they are not vulnerable to the disease; since they have the devices to prevent sexually transmitted diseases, and they could prevent the disease. The factor that prompts the boys to uptake the vaccine is that their genitalia becomes ugly due to the disease, and as a result, their partner will avoid them.
"The boys in my relatives are not impressed. I talk to them about these issues, but it is useless.
Unless I show them a picture of the disease and tell them you may be like this in the future, for example." (Healthy young participant, 25 years old) "Using condoms can make men think they are not vulnerable, and will never have a problem" (Psychologist, 31

years old)
The perceived severity is the belief that young people have about the losses from no-vaccination.
Most of the participants reported that the cause of vaccination in girls is the fear of cancer.

Contextual factors
This category consists of four subcategories, including education role, sex role, personality characteristics, and culture effects. 9 The participants mentioned that educated people find it easier to accept the health professionals' words.
"Education is important for both knowledge and acceptance of the health professionals' words and regular visits to the physician and various health professionals. Furthermore, it can be effective in vaccine uptake." (Young participant, 23

years old)
Women are usually more likely to uptake vaccines because of their gender role of being a mother.
Men, on the other hand, think that they do not need the vaccine because they are empowered. Men also consider the HPV vaccine a women-only vaccine and believe it has nothing to do with them.
"Boys think they do not get the disease at all because they think men are strong enough not to get it"

(Reproductive Health Specialist, 49 years old)
Risky individuals are more likely to uptake vaccines than others, and some do not uptake the vaccine due to the fear of the needle.
"After finding out about the vaccine, I did not uptake again because I was afraid of the needle."

External stimuli
This category consists of five subcategories, including peer effects, parental effects, physician effects, media effects, and observational learning.
In peer effects, usually, friends, who have knowledge, information, and experiences about the disease and HPV vaccine, can be useful in uptake the vaccine. Parents believe that uptake the vaccine by their children will increase their sexual freedom. Parents' lack of knowledge about HPV and its vaccine, family religiousness, and lack of belief in sexual intercourse outside marriage in their children can be the reasons for non-vaccination.

"Parents say that if their children get the vaccine, they can go and do any sexual activity." (Health Education and Health Promotion, 36 years old)
Concerning the physicians' effects on vaccine uptake, the participants believed that physicians could be a contributing factor to the vaccine uptake by scaring the patient about the disease risk. They also sometimes deny the illicit sex of young adults because of their religious affiliation.
"When physicians scare the patient about the disease and its complications, then patients search the internet, and they will be terrified. Then they come back and ask for the vaccine uptake."

(Gynecologist, 60 years old)
The media has created confusion in public with anti-vaccine advertising and misinformation about the vaccine side effects, and this can be a reason for non-vaccination.
In observational learning, the participants believed that young adults by modeling those who uptake the vaccine and seeing those who were protected with HPV vaccine uptake could be encouraged to uptake the vaccine.
"When a person sees those who uptake and finds that they have not been harmed and have been protected against the disease, it could be an encouragement to uptake the vaccine." (Health Psychologist, 40 years old)

Health services
This category consists of two subcategories, including costs and service coverage.
Most of the participants mentioned the high cost of the vaccine as a reason for non-vaccination. They also demanded the government free vaccines or covered by insurance. Another factor that has delayed vaccine uptake was that young adults were busy. Moreover, the vaccine requires a threeperiod injection, which creates a barrier to uptake. It creates a barrier to uptake. The participants believed that health care providers' behavior could also affect vaccine uptake and non-uptake. Illtreatment of the patient with the patient is a known cause of vaccine failure. Inappropriate physician's behavior with the patient is a known cause of non-uptake.
"The vaccine is costly, and it is a financial issue, and we do not uptake it." (Dermatologist, 64 years old) "One of the barriers to vaccine uptake can be time and being busy." (Reproductive Health Specialist,

years old)
The participants believed that one of the reasons for the non-uptake in young adults is the vaccine shortage and not be readily available as well as the distance from the uptake location and the inappropriate place for the vaccine uptake privacy.

Strategies to increase vaccine uptake in a low-vaccine country
During the interview, all participants were asked to make suggestions on vaccine uptake enhancement strategies, including providing free vaccine, vaccine availability, and the educational process (Table 4).

Discussion
In this study, factors affecting uptake and non-uptake HPV vaccine were evaluated from the perspective of health professionals and young adults, and also the strategies to increase vaccine uptake were identified.
In the present study, the majority of the participants mentioned the lack of knowledge on HPV and HPV vaccine as an effective factor for non-uptake vaccination. This may be due to a person's unwillingness to be aware of the disease and its vaccine, on the other hand, due to the culture and values of the society where talking about sex is thought taboo. Many studies have also reported that lack of HPV vaccine uptake is due to a lack of knowledge about the vaccine and related cancer in men and women [28][29][30][31].
The vaccine cost was reported as a major obstacle in this study. On average, each dose of the vaccine in Iran is 325,000 tomans, meaning that a complete vaccine series is 975,000 tomans. Many people spend more money on trivial things compared to the vaccine cost; since the importance of uptake, the vaccine has not yet been determined. Many people did not do the uptake vaccination due to its high cost. Many studies have also mentioned cost as a barrier to HPV vaccine uptake [32][33][34]. In the present study, girls tended uptake the vaccine due to the lack of trust in their future sexual partner, vulnerability to infectious diseases, fear of cancer, and boys due to fear of the appearance of the disease and transmission of the disease to their sexual partner. Some of the participants stated that some boys were reluctant to uptake vaccines because of the use of condoms to prevent sexually transmitted diseases and their invulnerability to the disease.
In the study of Kwan et al., some participants reported that they did not receive uptake vaccine by the age of 18 and above; since they did not intend to have sex [35]. Moreover, in the study of Marlow et al., they reported that specific religious beliefs about avoiding sexual intercourse outside marriage have caused some women to feel that the risk of HPV will not be worrying [36]. Many studies have also cited fear of cancer and its prevention as a reason for the vaccine uptake [37][38][39][40][41].
The present study showed that friends could be effective in the uptake of the vaccine. The study of Katz et al. showed that adults feel that peers provide inaccurate information about sex to their children and encourage one another to engage in high-risk behaviors. At the same time, adolescents acknowledge the positive impact of peers, especially on encouraging uptake vaccines [32]. The participants in the study by Francis et al. also pointed to the role of friends in decision making for health services [42].
In the present study, factors preventing parents from vaccination of their children included parents' difficulty in talking to their children about sex issues, beliefs about sexual freedom in children with vaccination, and parents' fear of children being infected with the disease by vaccine uptake, and belief in lack of sexual intercourse outside marriage in children. Several studies have also pointed to these factors [35, 37-39, 43, 44].

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Physicians also had an encouraging and inhibiting role in the vaccine uptake. Physicians' advice may be more effective than others in the uptake of the vaccine. Sometimes physicians may also have religious bias and deny having the disease and do not consider the vaccine uptake necessity. Several studies have also pointed to these factors [33,45,46].
In the present study, the participants noted the inaccurate advertising about the vaccine in the mass media as well as creating confusion among the public, which may cause non-uptake of the vaccine.
The study by Cover et al. showed that the media, with positive and negative messages, may affect people's decision to uptake the vaccine [40].
In the current study, taboo and stigma are reported as the other factors of non-uptake of the vaccine.
In most of the areas studied (lack of knowledge about HPV disease and the HPV vaccine, perceived threat, external stimuli), there are traces of taboo and stigma. They included parents' shame about talking about sex with children, fewer men's referrals to the physician due to their shame, lack of vaccination due to the prevailing atmosphere in the society and family, and misbehavior of the staff with people with sexual problems. Several studies have also pointed to these factors [35,[47][48][49].
In the present study, the most important recommendations of young adults and health professionals for increasing vaccine uptake strategies are to educate different people to become familiar with HPV and HPV vaccine. By focusing on the education process, which includes the trainer, the learner, the conditions of education, the content of the education, the timing and channels of knowledge transfer and awareness, the proper training can be implemented.
In the present study, the participants preferably suggested the health professionals as trainers; since they are more reliable and knowledgeable. Moreover, the importance of the role of virtual networks and their impact on vaccine uptake, including mass media, can be the essential source of information for health professionals. Various studies have also emphasized the role of physicians and the media in knowledge transfer [35,39,43].
Given the culture of the society, it is difficult to talk about sex issues, especially sexually transmitted diseases. These issues are better to be educated individually. In the study by Yarmohammadi et al., it was believed to provide sex education individually [50]. Information should also be provided step-by-step from school to the elderly period, and there should be proper planning and compulsory education in sexually transmitted diseases. Health education models should also be used to change behavior in educational content design. In the study by Ferrer et al., most female participants reported that they received the vaccine information through school and classrooms [51].
The learner could be teenagers, youth, parents, and health professionals, educational content is designed for each one according to their knowledge and awareness, as well as the cultures and values of each country. Fontenot's study showed that the family had a facilitating role in vaccine uptake and should be educated about HPV and the vaccine [48].
In the study by Tissot et al., the participants generally agreed that written material should be provided separately for teenagers, youth, and parents. They also suggested that educational materials, including graphic images of HPV, are effective in emphasizing the infection for teenagers and youth [52].

Strengths
The strength of this study was that some of the health professionals and young adults were mothers and stated the factors of uptake and non-uptake vaccinate from their maternal perspective, which made the study information more complete Given that the study results are also transferable to younger ages, the other strength of the study was that the maximum variable was considered in terms of demographic characteristics between the participants. The study also asked the views of both sexes about the vaccine uptake, and the important strength was that the young adults in the study decided to the vaccine uptake.

Limitations
This study also had limitations. Qualitative studies are not inherently generalizable; therefore, more attention needs to be paid to the population when using the findings of this study. Also, it was difficult to interview HPV patient participants and those who received the vaccine due to the community culture.

Conclusion
In conclusion, our study indicates that deciding about uptake or non-uptake of the HPV vaccine is a multilateral decision for young adults. With associated with knowledge, trust in the vaccine benefit, social norms and values, perceived danger of HPV vaccine and cervical cancer, parental approval, sex partners, friends and doctors, and sexual activity. This study also helps to increase HPV vaccine uptake in Iranian youth. If vaccination coverage has to be improved, there is a pressing need for culture-appropriate education about the HPV vaccine and health care providers' recommendations.    27 costs for the government, it has been suggested to provide free vaccination for those at risk.

Vaccine availability:
Given the scarcity of the vaccine, the government should provide facilities that make it easy for everyone to access the vaccine and make it available to different groups of society.
Some vaccine types should be available to upta Psychologist, 31 years old)

Educating and informing:
The most important strategy mentioned by the participants was to educate different groups of people to raise awareness and sexual literacy in the community. According to the information obtained, the participants demanded a public educational process as follows.

1-Audience Groups:
The participants believed that the first step is that the community leaders, as well as celebrities, who are influential, including religious people, athletes, actors, should be aware of HPV and its vaccine; since they are as a factor for the vaccine uptake.
The health system should also be responsible for educating parents, Educating young parents about sex and sexually transmitted diseases and how to later inform their children was also a part of the participants' suggestions to increase knowledge.

3-The appropriate time to provide education:
The participants believed that education should take place at all stages of life, at junior high school and high school levels before sexual activity Furthermore, education for sexual abstinence when someone is single, Including What are the high-risk behaviors? Different preventive methods, etc.
Include pre-marriage counseling on sexually transmitted diseases, including HPV and its related vaccine.
Education is at high school and junior high scho (urologist, 46 years old) Sexual abstinence is the practice of refraining f of sexual activity until marriage, educateding w means, and how to prevent it They can also include education in premarital c years old)

4-Educational channels:
The participants believed that relevant experts should provide education in mass media, such as television, which plays an essential role in informing people. First sex programs need to be shown on channels, such as health channels and then slowly in popular channels.
Advertising should also be carried out on rural and city health networks, and information has to be provided to the patients in clinics by physicians.
Mass media, radio, and television will play an im uptake (dermatologist, 64 years old) Doctor is very effective in uptake the vaccine. F another illness. The doctor then gives you this i for example, this is a new disease, and you mu and so on. (young participant, 27 years old)

5-How to present the content:
The participants believed that because it is taboo to talk about sex, it is better to have individual education for young adults.
There are also many models of behavior change in health education. The most important of them are the Health Belief Model and the Transtheoretical model and other models that can motivate behavior change. It is advisable to develop materials on sex and related diseases and their prevention based on these models.
Some of the participants believed that media education is not valuable; since it is one-sided, and it is better to have face-to-face and question In my opinion on stigma issues such as HPV dis counseling should be provided (health educatio old) We discuss how social liberation in the transthe affect other people, and also how the incentive increase the motivation to uptake the vaccine a education and health promotion specialist, 36 y The media is one-sided, such as television, and people. However, when someone explains to 20 one disagrees and talks about the issue, there 29 and answer education. the TV does not answer (young participant, 25

6-Educational Conditions:
Education should take place in a way that information is told very slowly and consistently, and then acceptance and analysis of the contents should be done. It requires planning and compulsion.
Regarding sensitive issues, such as sex, a supportive environment should be created based on health promotion principles both in education and the rest of the stages.