Human papillomavirus (HPV) infection is considered the most frequent sexually transmitted infection in the world (1). Several studies suggest a high lifetime probability of HPV acquisition early in life, as reported by a US cohort, in which more than 80% of women and men acquire HPV by the age of 45 years (2). HPV infection can lead to a variety of consequences besides cervical cancer, such as genital warts and oropharyngeal, penile, anal, vulvar, or vaginal cancer (3).

Transgender women are not exempted from HPV risk infection. Indeed, some studies demonstrate a high prevalence of high-risk serotypes and the presence of anogenital warts in adult trans women, such as that of Brown et al. (2016), which shows that up to 96% of trans women have HPV infection, 58.8% of whom were high-risk serotypes and up to 19.1% have anogenital warts (4). Along this line, Jalil et al. (2021) report that up to 77.9% of trans women were infected with HPV, with 60.7% being high-risk serotypes (5). In addition, an American study reports that transsexual women have a higher prevalence of anal HPV infection than men who have sex with men, 88.6% versus 70.9%, respectively (6). Moreover, although the prevalence of neovaginal infection is unknown, five cases of squamous cell carcinoma have been related to HPV infection in the neovagina of transgender women, some of which are at an advanced stage, perhaps due to the low concern about it (7–11).

HPV vaccination programs are mainly designed to protect people from cervical cancer. However, in recent years, scientific evidence suggests that the vaccine may protect against other neoplastic entities (12, 13). Furthermore, the World Health Organization recommends vaccination in adolescents of both genders (14). Main vaccination programs are focused on cisgender female adolescents prior to the first sexual intercourse, approximately 12–14 years old, and high-risk groups, such as those engaged in prostitution, people in contact with HIV, conizated women, and men who have sex with men (15). However, trans women are not included, probably due to a lack of knowledge, which could have a negative impact on their health. In fact, in a survey in which two trans women were recruited, only one received recommendation for HPV vaccination (16). Such data suggest missed opportunities to address the need for HPV vaccination among transgender people.

Achieving a high vaccination rate is important in the adolescent population, but many factors contribute to vaccination refusal by adolescents and their families (17). Many studies show the impact of acceptance or denial of the vaccination according to the opinion of the main caregiver of adolescents. Some factors, such as efficacy, the fear related to vaccine safety, or a poor knowledge about risk and consequences of HPV infection, are reported to be crucial when choosing to vaccinate or not (18, 19).

Currently, there is no published study that focused on the feelings and knowledge of main caregivers of trans adolescents, in order to improve the adherence to vaccination. Our aim is to determine the main trans women caregivers’ knowledge about HPV infection and risk, and to detect which factors could influence the intention of vaccination.

A cross-sectional study was conducted based on interviews of main caregivers of adolescents under 16 years old followed up in two reference centers with a multidisciplinary Sex Reassignment Treatment Unit: Hospital Puerta del Mar (Cádiz, Spain) and Hospital Universitario Reina Sofia (Cordoba, Spain). Inclusion criteria were as follows: main caregivers of transgender women between 9 and 16 years old who were involved in Sex Reassignment Treatment Units between January 2022 and July 2022, completed the questionnaire, and signed the consent form.

The survey instrument was HPV-related diseases Knowledge Transwomen questionnaire (HPV-TQ), a 19-item self-administered questionnaire with True–False forced-response questions based on a validated survey but adapted to the transgender population (20). It covers basic knowledge of HPV infection as its characteristics, including transmission, viral properties, treatment, prevalence, vaccination, perception of sexual risk behavior, and specific risk in trans women. The content, readability, and comprehensiveness of the questionnaire were reviewed by clinicians and health educators. Answers were evaluated. Correct answers were scored as 1 point, and wrong answers received 0 points. The final score was the result of the sum of all points, ranging from 0 to 19. This score was converted into percentage, standardized from 0 to 100. A score equal to and/or over 70% was classified as high HPV knowledge. HPV vaccination status and demographic and clinical data were collected from the clinical history of trans girls.

All participants provided a written informed consent before data collection in accordance with the Declaration of Helsinki, and researchers guaranteed the anonymity of data. The study was approved by the Ethics Committee of Puerta del Mar University Hospital (ethical approval code number PEIBA 0474-N-22).

Statistical analysis was performed with SPSS version 23.0 (IBM, Armonk, NY, USA). Descriptive statistics were calculated for all variables. Continuous measures were summarized by using mean and standard deviation, and dichotomous measures were summarized by using proportions. Student’s t-test was performed to compare continuous variables and χ ² was used when proportions are compared. p < 0.05 was considered statistically significant.

Gay, bisexual, and other men who have sex with men and transgender women are disproportionately affected by HPV. HPV vaccination is most effective when given before exposure to HPV through sexual activity. Vaccination is routinely recommended in some countries such as USA for adolescents at age 11–12 years, with catch-up vaccination through age 26 years. However, Meites et al. (2022) showed a median age at first dose of 19 years and a median age at first sexual intercourse of 17 years; 493 (73.3%) reported that their age at first dose was older than their age at first sexual intercourse (21). Spain probably had a similar situation, which could explain the low vaccination rate in the recommended age group. National vaccination surveys reported that our region, Andalusia (Spain), has the lowest vaccination rate in the country. Only 75% of adolescent cisgender girls had the first vaccine dose, and 59.9% had the second one (22), but adolescent trans girls have lower rates: only 28.9% of those over 12 years old have been vaccinated. The rate in our study might not be considered the real prevalence, because not all trans adolescents of the region were evaluated in our study, but the rate could be representative of the population. Also, we observed a low vaccination intention; only 16.9% of trans girl main caregivers considered the vaccination important for their minor children. Similar data were reported in studies focused on main caregivers of adolescent cisgender boys (23, 24), cisgender adult men (25), and men who have sex with men, probably because of the lack of knowledge of the risk for oral, penile, and anal cancer (26), and because HPV infection was considered an issue only for cisgender girls or women, due to health marketing and campaign efforts to achieve higher vaccination in this population (24).

The group of main caregivers who were highly knowledgeable about HPV showed a significantly longer follow-up at our specialized units, which might be explained by the fact that related information about risk of HPV in trans girls could be provided by gender diversity unit specialists who are knowledgeable about the importance of HPV vaccination. Vaccination in our region is programmed in primary care centers. A study in Andalusian primary care revealed that low knowledge of professionals leads to doubts in vaccination as well as unclear information provided to patients and families (27). In addition, professionals need to be sensitive to the specific health problems of trans women, such as HPV-related diseases, in order to reduce stigma and healthcare barriers (28). It is important for professionals to transmit reliable information to main caregivers and adolescent trans girls.

A similar situation has been experienced in other countries. In a 2014 survey conducted in USA involving rural participants enrolled online that included 23 transgender women who were age-eligible for HPV vaccination, only one reported receiving a healthcare provider recommendation for HPV vaccination, and only one reported ever receiving ≥1 dose of HPV vaccine. Such data suggest missed opportunities to address the need for HPV vaccination among transgender people as well as in our country (29). Increasing both routine and catch-up vaccination will improve coverage among transgender women (21).

Several studies revealed the main predictors of vaccination, which included, apart from healthcare provider recommendation, younger age, having a healthcare visit in the past year, receiving other recommended vaccinations, and living with HIV (21, 29, 30). Another interesting point is reported by Pho et al. (2022), which is associated with online health information seeking and HPV vaccination (31). Decreased reporting of HPV vaccination among trans people after searching for vaccine information online suggests vaccine hesitancy, which may potentially be related to the quality of online content. Increased reporting of vaccination after using social media may be related to peer validation. Future studies should investigate potential deterrents to HPV vaccination in online health information to enhance its effectiveness and further explore which aspects of social media might increase vaccine uptake among trans people.

Although other studies revealed higher knowledge in vaccinated adolescents’ parents (32), we did not observe this effect, because almost all adolescent trans girls in our study were vaccinated without any specific motivation; they just followed the cis girl program. We observed that a previous history of HPV disease in the first-line family is associated with a higher knowledge score and higher intention of vaccination. Other studies found an inverse correlation between knowledge and age of main caregivers (33), but our data did not support this. Moreover, educational level is reported as important. Higher HPV knowledge has been related to higher educational attainment (34); however, our study showed equally distributed educational levels. Gender and ethnicity influence could not be analyzed in our study because almost all participants were Caucasian and women.

Mean knowledge in our study was acceptable but some questions had a low proportion of correct responses such as those related to clinical presentation, natural history of HPV infection, diagnosis method, and treatment. This could reflect ignorance about basic aspects of HPV infection. These findings are similar to a study involving the main caregivers of adolescent cis boys from UK. Firstly, in the question “HPV can be cured by antibiotics” in our study, only 43.1% of main caregivers answered correctly, compared to 48.5% in the adolescent cis boys’ main caregiver study (23). Also, the question “Most sexually active people will get HPV at some point in their lives” had 41.5% and 32.3% correct responses, respectively (23). Interestingly, oropharyngeal infection by HPV is unknown for many main caregivers in our study; only 41.5% knew that it could be found in the mouth, lower than that reported by the adolescent cis boys’ main caregiver survey study (49.5%) (23) and that reported by a study in an adult population in USA (49.3%) (20).

The strength of our study resides in the fact that limited data about HPV in the trans population are available (35). In fact, in USA, database searches and manual searching yielded 843 citations. After screening, eight articles were retained in the review. Seven were cross-sectional studies and one was a qualitative focus group. The low proportion of transgender participants in the retained studies highlights a gap in knowledge about HPV vaccination among this population. Future studies of HPV vaccination should recruit trans people to better represent their perspectives and data (31). There are some limitations in our study, such as having a small sample size and the low diversity in caregivers, because most of them were mothers. Two main caregivers refused to participate. Thus, our results could be susceptible to selection bias because the main caregivers who participated might be more health conscious and curious about HPV. In that case, HPV knowledge could be lower if this is true.

This study showed a low vaccination proportion, only 21.5%. Also, 21.5% of main caregivers of unvaccinated adolescent trans girls intend to be vaccinated. We observe that intention of vaccination is related to HPV knowledge. Knowledge in HPV was related to a previous family history of HPV-related disease, maternal HPV vaccination, and longer time of follow-up in our units. The results should encourage the development and implementation of health education programs that discuss the HPV vaccine and its benefits for trans women at early age. General recognition and approval of vaccination programs for trans women by health international institutions and campaigns focused on main caregivers to increase knowledge and awareness about the virus and vaccination can help raise the vaccination rate and improve health equality.

The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author.

The studies involving human participants were reviewed and approved by COMITÉ DE ÉTICA DE LA INVESTIGACIÓN DE CÁDIZ. Written informed consent to participate in this study was provided by the participants’ legal guardian/next of kin.

JD-R and IM-G conceptualized and designed the study, contributed to the clinical recruitment of participants, supervised the database, performed statistical analyses, drafted the initial manuscript, revised it, and wrote the final version. CB-C performed the dataset and reviewed and revised the manuscript. A-BA-J reviewed the study design, contributed to the clinical recruitment of participants, and reviewed and revised the manuscript for the final version. All authors contributed to the article and approved the submitted version.