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Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
Annu Rev Public Health. Author manuscript; available in PMC 2011 April 21.
Published in final edited form as:
PMCID: PMC2925431

Integrating Clinical, Community, and Policy Perspectives on HPV Vaccination

María E. Fernández, PhD,1 Jennifer D. Allen, DSc, MPH,2,3 Ritesh Mistry, PhD,4 and Jessica A. Kahn, MD MPH5


Infection with genital human papillomavirus (HPV) may cause anogenital cancers, oropharyngeal cancers, anogenital warts, and respiratory papillomas. Two prophylactic vaccines (a bivalent and a quadrivalent vaccine) are now licensed and currently in use in a number of countries. Both vaccines prevent infection with HPV-16 and HPV-18, which together cause approximately 70% of cervical cancers, and clinical trials have demonstrated 90%-100% efficacy in preventing precancerous cervical lesions attributable to HPV-16 and HPV-18. One vaccine also prevents HPV-6 and HPV-11, which cause 90% of genital warts. A growing literature describes associations between psychosocial, interpersonal, organizational, and societal factors that influence HPV vaccination acceptability. This paper summarizes the current literature and presents an integrated perspective, taking into account these diverse influences. The resulting integrated model can be used as a heuristic tool for organizing factors at multiple levels to guide intervention development and future research.

Keywords: human papillomavirus, vaccine, psychosocial factors, theory, policy, health care systems


Human papillomaviruses (HPVs) are DNA viruses that infect the skin or mucosa. Genital HPVs are highly contagious and usually acquired through sexual contact, both penetrative and non-penetrative. Infection often occurs within the first few months after sexual initiation (112), and peak incidence occurs in 15- to 24-year-old men and women (36, 110). Infection with high-risk or cancer-associated HPV types (e.g. HPV-16, HPV-18) may cause anogenital cancers such as cervical cancer as well as oropharyngeal cancers. Infection with low-risk types (e.g. HPV-6, HPV-11) may cause anogenital warts and respiratory papillomas (15).

Two prophylactic vaccines, a bivalent (HPV-16, -18) vaccine and a quadrivalent (HPV-6, -11, -16, -18) vaccine, are now licensed and currently in use in a number of countries. Both vaccines prevent infection with HPV-16 and HPV-18, which together cause approximately 70% of cervical cancers. The quadrivalent HPV vaccine also prevents infection with HPV-6 and HPV-11, which cause approximately 90% of anogenital warts.

While both HPV vaccines are expected to decrease morbidity and mortality related to HPV-associated diseases, the public health impact will depend upon vaccine uptake in the general population and in particular among groups disproportionately affected by these conditions. Recent estimates indicate current HPV vaccination rates are low among girls in the target age range (approximately 25%) and even lower among those at highest risk (37). HPV vaccine acceptability among clinicians, parents, and adolescents is likely to have a substantial impact on vaccine uptake. To date, the vast majority of studies have examined individual characteristics associated with vaccine acceptability (5, 9, 10, 16, 19, 20, 26, 28, 31, 32, 33, 34, 35, 38, 50, 52, 61, 72, 81, 83, 85, 87, 89, 96, 98, 103, 104, 105, 113, 114, 116). Other studies have identified external influences on vaccine uptake including provider recommendation and vaccine availability (30, 66, 73, 77, 78, 88, 93, 95). Successful vaccination programs require an understanding of individual factors influencing vaccination decisions; broader issues related to access, processes of care delivery, societal vaccine policies; and the relationships among these various factors. Therefore, a comprehensive framework to understand HPV vaccine utilization and guide future research and vaccine promotion activities is needed (76).

The purpose of this paper is to 1) present a review of clinical data related to HPV vaccination; 2) summarize personal, interpersonal, provider, organizational, and policy factors influencing HPV vaccination uptake; and 3) propose a conceptual model for integrating the factors that affect access to and uptake of the vaccine. In this paper we organize existing findings related to determinants of HPV vaccination, discuss implications of available evidence for the development of comprehensive programs that address mediators of vaccine uptake across multiple levels of influence, and discuss remaining challenges and areas of needed research.

HPV Vaccines

Globally, cervical cancer is the second most common cancer among women and is thought to be the largest single cause of years of life lost to cancer in low-income countries (3, 24). Approximately 490,000 women are diagnosed and 270,000 die from cervical cancer each year (24). In the U.S., despite organized cervical cancer prevention programs involving regular Pap screening in reproductive-age women, approximately 11,000 women are still diagnosed with cervical cancer and 4,000 women die from the disease annually ( Substantial racial, ethnic, and socioeconomic disparities exist for HPV infection, cervical cancer incidence, and cervical cancer mortality (45, 74). Direct costs associated with the prevention and treatment of HPV-related disease are at least 4 billion U.S. dollars (USD) per year, and indirect costs such as productivity losses add 1.3 USD per year (63, 64).

Clinical trials of the bivalent vaccine have been conducted in women 10-55 and men 10-18 years of age; trials of the quadrivalent vaccine have been conducted in women 9-45 and men 10-26 years of age (12, 18, 47, 48, 57, 58, 71, 92, 94). The clinical endpoints in efficacy studies of both vaccines include cervical intraepithelial neoplasia (CIN) 2/3 and adenocarcinoma in-situ (AIS), generally considered to be cervical cancer precursors, as well as other anogenital cancer precursors (e.g. anal intraepithelial neoplasia). Anogenital warts are also an endpoint for clinical trials of the quadrivalent vaccine.

Information about the immunogenicity and efficacy of the bivalent and quadrivalent HPV vaccines is available from several international, randomized clinical trials. Seroconversion rates are ≥ 97.5% for both vaccines (18, 48, 92, 94). Studies suggest that although immune responses tend to be durable for at least five years after vaccination, antibody levels do eventually decline, especially for HPV-18 (44, 57, 58, 108). However, lower antibody levels do not appear to lead to breakthrough disease, possibly due to immune memory (70). Data from ongoing clinical trials will be needed to confirm the duration of immunity and to determine whether there will be a need for a booster dose. Both HPV vaccines appear to generate cross-neutralizing antibodies against related HPV types not targeted by the vaccines, and therefore may provide protection against disease caused by those types (7, 23, 69).

Clinical trials of both the bivalent and quadrivalent vaccines have demonstrated 90%-100% efficacy in preventing precancerous cervical lesions attributable to HPV-16 and -18, among women who were uninfected with those HPV types before vaccination and who received all three vaccine doses (6, 47, 48, 57, 71, 108). The quadrivalent vaccine is also highly effective in preventing anogenital disease caused by HPV-6 and -11 (48). Efficacy is substantially lower among women who may be HPV-infected at the time of vaccination (47), because vaccination does not protect against HPV-16 or -18 infection or disease in women infected with those HPV types at the time of vaccination (47, 48, 92). In addition, vaccination does not facilitate clearance of HPV-16 and -18 in infected women (59). Thus, HPV vaccines will have the most significant impact on individual and population health if vaccination is targeted to early adolescents, prior to sexual initiation and thus before HPV acquisition.

Extensive clinical trials data and post-marketing safety monitoring data have demonstrated that both HPV vaccines are generally safe and well-tolerated. The Centers for Disease Control and Prevention (CDC) in the U.S. ( and the World Health Organization (WHO) Global Advisory Committee on Vaccine Safety have concluded that data support the safety of both HPV vaccines ( Mild injection-site adverse events (e.g. pain, redness, itching, and swelling) are fairly common, while mild systemic adverse events such as low-grade fevers are uncommon. Serious adverse events were rare in the clinical trials, and did not occur more frequently in vaccine than placebo participants (47, 92). Post-licensing studies to evaluate quadrivalent vaccine safety, and especially to detect rare adverse events, have been conducted by the CDC, other public health organizations globally, and the vaccine manufacturers since 2006. Rare post-marketing reports of serious illness or death occurring at some point after receipt of the quadrivalent vaccine have been reported, but none of these events appear to be caused by the vaccine (

Both the quadrivalent and bivalent vaccines have been licensed in many countries, and in those countries with national immunization programs that have established recommendations for HPV vaccination, there is general consensus that young adolescent girls should be targeted for vaccination (80). In the U.S., it is recommended that HPV vaccination be targeted to 11- to 12-year-old girls, and catch-up immunization is also recommended for 13- to 26-year-old women (84).

In summary, HPV vaccines are available and recommended for use in many countries. The data thus far suggest that they are safe, and are highly effective when administered to young women who are uninfected with HPV types included in the vaccine. However, the public health impact of vaccination can only be realized if vaccine uptake is high in young women who have not yet initiated sexual intercourse, and are therefore unlikely to be infected with HPV. Thus, integrating community and policy perspectives related to HPV vaccine access and uptake is critical to maximizing the potential health impact of these vaccines.

Factors Influencing HPV Vaccination

The existing literature on HPV vaccination includes many studies that describe associations between various individual and healthcare factors and HPV vaccination. However, no logic model or conceptual framework has been described that presents an integrated perspective of HPV vaccination and that can be used to guide intervention development and future research. The majority of studies that describe psychosocial factors associated with vaccine acceptability or intent measure constructs from theories including the Health Belief Model (17), Theory of Reasoned Action (4), and Social Cognitive Theory (11), yet often there is no mention of the theoretical model that guided selection of hypothesized determinants (JD Allen, GD Coronado, RS Williams, B Glenn, C Escoffery, M Fernandez, RA Tuff, KM Wilson, PD Mullen. A systematic review of measures used in studies to assess acceptability of the human papillomavirus (HPV) vaccine. Manuscript under review.) Studies of personal, organizational, or societal factors that are associated with vaccine acceptability, which will be summarized next, each provide only a partial perspective on the multitude of factors that may influence vaccine uptake. The evidence-based conceptual model that will be described following the literature review facilitates consideration of multiple determinants of vaccination across a number of theoretical models of health behavior. As such, it provides a useful framework for examining the impact of personal, interpersonal; organizational; and broader community and societal factors on vaccination (11, 13, 56, 86). The model also provides a framework for understanding the complex interrelationships between these multiple levels of influence, which often have a profound impact on individual decision-making and behavior.

Personal Factors Influencing HPV Vaccination

Parental acceptability for HPV vaccination

Because the HPV vaccine is recommended for young adolescent girls, parents will have authority for making most decisions about vaccination. Therefore, the success of programs designed to maximize vaccine uptake will largely depend upon parental decision-making. A number of quantitative studies have examined parental willingness to vaccinate their daughters. Most were conducted prior to licensure of the vaccine (9, 20, 26, 31, 32, 33, 50, 81, 98, 103, 114, 116). Approximately half of these were conducted in the U.S. (9, 28, 31, 33, 38, 50, 72, 96, 103, 104, 116). Most have been conducted in clinical settings (9, 26, 31, 33, 34, 38, 50, 96, 98, 105, 116), and many have been conducted in schools (20, 32, 83, 85, 105, 114). Only a few have been population-based (20, 28, 72, 89).

Overall, knowledge about HPV and its relationship to cervical cancer among parents is low. In quantitative studies conducted post-licensure and that assessed knowledge, 60%-89% of parents reported that they were not aware of HPV until the time of the survey (20, 34, 38, 83, 89). In some cross-sectional studies, an association between HPV knowledge and vaccine acceptability has been observed (38, 81, 114). In addition, increased willingness to vaccinate following provision of factual information about HPV has been observed in some (26, 31, 32), but not all, studies (33).

Despite low levels of knowledge demonstrated across these studies (79), the majority of parents (70% to 85%) expressed a willingness to vaccinate their daughter(s) (9, 20, 28, 89). Two recent studies have reported lower levels of willingness to vaccinate (48% and 52%, respectively)(26, 72). Some (33, 72, 85) but not all (96, 116) studies have shown parental acceptability of vaccination may vary with the child's age, with parents being more willing to vaccinate daughters who are older than the age recommended by the Advisory Committee on Immunization Practices (ACIP) (11-12).

Parental vaccine acceptability has also been associated with a number of beliefs and attitudes suggested by theories of health behavior, the Health Belief Model (17), being the most common. Parents who feel their child is susceptible to HPV or to cervical cancer (33, 38, 50), worry about HPV or sexually transmitted infections (20, 26), believe the vaccine is efficacious and will afford benefits (9, 20, 31, 32, 33, 38, 50, 72, 81, 116), and perceive few barriers to accessing the vaccine (38, 98) are more likely to report willingness to vaccinate. Perceived severity of HPV and associated health consequences was related to parental attitudes toward vaccination in some (9, 38, 72, 85, 116), but not all (33) studies. Positive attitudes toward vaccines in general have also been associated with parental intention to obtain the HPV vaccine for one's daughter (72). Social influences, such as the approval of significant others or the perception that vaccination is normative, have been associated with vaccine acceptability (33, 34, 72, 85, 89). Across studies, the importance of provider endorsement of the vaccine is clear (33, 34, 50, 98).

By far, the major concerns expressed by parents are related to vaccine safety and potential adverse behavioral consequences. Those who believe the vaccine to be safe (20, 31, 32, 50), or have more positive attitudes toward vaccines (28, 72, 89, 114) are substantially more likely to report that they would vaccinate their children. In a number of studies, parents expressed concern that vaccination would send a message to their children condoning sex or could encourage earlier age of sexual initiation, and this was associated with lower rates of vaccine intentions (26, 28, 31, 114). The proportion of parents reporting concerns about sexual disinhibition varies considerably across studies, with some studies reporting extremely low prevalence of this concern (34, 83, 89) and others reporting this to be an issue for as much as a quarter to a third of study subjects (98, 105). In a study of Texas physicians, at least half noted that parents in their practice had refused the HPV vaccine because of concerns about vaccine safety, lack of parental education, negative media reports about the vaccine, and parental concern that their consent would imply that they condone premarital sexual intercourse (73).

Few studies have systematically examined the association between socio-demographic characteristics and acceptability of vaccination. Those examining these relationships have yielded mixed results, with some finding no impact of parental age, educational level or marital status (83), and others finding differences across race/ethnicity (28, 85), education and income levels (31).

Acceptability of receiving the vaccine for oneself

Although personal intentions to receive the HPV vaccine and vaccine acceptability among adults, young adults or adolescents vary substantially, from 48% (72) to 96% (16), generally acceptability is high, in the range of 66% to 86% (19, 35, 38, 50, 52, 61, 76, 87, 98, 104, 114).

Some studies have reported factors associated with vaccine acceptability or intent for oneself to receive the vaccine. Constructs most often assessed have included knowledge, perceived susceptibility, perceived severity, social influence, perceived effectiveness, barriers to vaccination, and perceived benefits. (5, 19, 22, 33, 38, 39, 40, 46, 49, 50, 51, 52, 53, 60, 75, 76, 87, 113, 114).

Social influences, such as the perception that one's parents approve of vaccination, predicted vaccine acceptability among adolescents and young adults (19, 27). Other studies found perceived provider endorsement of the vaccine was associated with increased vaccine acceptability (27, 50, 117). Perceived social norms (the belief that others like them will get vaccinated) also has been shown to predict vaccine acceptability (5, 49). In a recent study, subjective norms (belief one's parents, partners, and/or clinicians supported vaccination) influenced receipt of at least one HPV vaccine dose (27).

Some studies have demonstrated a relationship between perceived severity of HPV or cervical cancer and higher vaccine acceptability (40, 76). Other studies, however, have not shown this relationship (19, 33, 75).

Beliefs about the safety of the HPV vaccine were positively associated with vaccine acceptability in some studies (19, 50), and concerns about potential side effects were negatively associated with acceptability in others (31, 87, 103, 113). Perceived effectiveness of the vaccine (19, 38, 39, 50, 118) and low cost (19, 39, 49, 98, 113, 117) were also associated with acceptability.

Environmental Factors Influencing HPV Vaccination


It is well-established that clinician recommendation is one of the most important predictors of a parent's decision to accept vaccination for his or her child (29, 55, 97). Therefore, understanding clinicians' intention to recommend HPV vaccines and actual HPV vaccine recommendations is crucial, as identification of those factors predicting intentions and recommendations may help to guide the design of interventions. Studies conducted prior to vaccine licensure demonstrated that physicians reported high intention to recommend HPV vaccines, although some studies suggested that intentions varied; clinicians reported higher intention to recommend a vaccine to girls compared to boys, and to older compared to younger children (30, 66, 77, 78, 95). In a qualitative study of pediatricians, preferences for vaccinating girls were based primarily on the belief that girls would derive a greater health benefit from vaccination than boys, and the concern that it would be difficult to convince boys and their parents that boys should be vaccinated (77). Those who intended to vaccinate pre-adolescents cited the importance of vaccinating prior to sexual initiation, while those who preferred to vaccinate older adolescents perceived their patients to be at low risk for HPV or were concerned about the need to discuss sexuality when recommending the HPV vaccine.

Studies conducted after HPV vaccine licensing generally confirm the findings of earlier studies. In a study of Texas primary care physicians conducted two years after the HPV vaccine was licensed in the U.S., fewer than half reported that they always recommended the HPV vaccine to 11- to 12-year-old girls (73). Two-thirds reported always vaccinating 13- to 17-year-old girls, suggesting that parents or physicians may be delaying vaccination until girls are older than 12 years of age. The finding that providers are reluctant to vaccinate young adolescents is problematic because by ninth grade, approximately one-third of U.S. adolescents have initiated sexual intercourse (25). Prophylactic HPV vaccines will not prevent HPV-related disease caused by a vaccine-type HPV if a young woman is infected with that HPV type at the time of vaccination. Thus, the public health impact of vaccination will not be maximized if vaccination is delayed in young women until after sexual initiation, as HPV is often acquired soon after sexual initiation (112).

Research has also shown that clinicians' personal characteristics, practice characteristics, knowledge about HPV, and attitudes are associated with intention to recommend and actual recommendation of HPV vaccines. Key attitudes include: belief that influential organizations endorse vaccination, perceived susceptibility of one's patients to HPV-related disease, perceived severity of HPV-related disease (particularly cervical cancer), and benefits and barriers to vaccination (77, 78, 88, 93, 95). In one study, factors that independently predicted a clinician's recommendation to vaccinate an 11-12 year-old girl included: percentage of patients with Medicaid, academic vs. non-academic practice, office procedures to maximize vaccination, HPV knowledge, valuing HPV vaccine information from professional organizations and professional conferences, belief in mandated HPV vaccination, and barriers to vaccination (73).


In most countries, the successful introduction of a new vaccine depends upon the following steps: the vaccine is licensed by a regulatory agency, a national immunization program establishes vaccination recommendations, professional organizations provide guidance for vaccination, new infrastructure is developed or existing infrastructure utilized to ensure vaccine delivery, the cost of vaccination is financed by public or private mechanisms, and individuals at risk for disease then access the vaccine (102).

Both the quadrivalent and bivalent vaccines have been licensed in many countries and some national immunization programs have established recommendations for vaccination(80). However, there are two major organizational barriers to HPV vaccine implementation. First, the infrastructure for implementation of an adolescent vaccination program is poorly developed in many countries, particularly low- and middle-income countries. School-based programs may be an efficient mechanism for adolescent vaccination (21); however, vaccine coverage will be limited in countries where young adolescent girls are not likely to be in school. Public health campaigns, such as the Expanded Program on Immunization (EPI), generally are designed to target infants or young children, and may not effectively reach adolescents. Thus, each country must develop a service delivery strategy for HPV vaccines, based upon what is feasible and culturally acceptable (115).

Second, even in countries where adolescent vaccination programs are well-established, evidence-based systems to maximize vaccine recommendations and uptake are not in place in many offices, schools, public health clinics, and other settings where vaccination takes place. These include recall and reminder systems (e.g. calls or letters to patients or families to remind them to make or keep vaccine appointments); clinician reminders for vaccination; auditing and feedback to clinicians; standing orders for vaccination; and regional immunization registries (107). Such systems appear to be effective in increasing vaccination rates in both children and adults (68, 106). The establishment of a country-specific service delivery strategies as well as the implementation of specific systems to ensure high rates of vaccination will be critical for maximizing HPV vaccine uptake (100).

Community and societal

The currently available quadrivalent HPV vaccine is one of the most costly of all available pediatric and adult vaccines. According to the CDC, the cost of the vaccine for the private sector is estimated at about 130 USD per dose (390 USD for three doses). The CDC negotiated price is currently 100 USD per dose ( High cost is an important barrier to obtaining HPV vaccination (22), as has been reported by studies in a variety of populations (19, 46, 76, 117). Insurance coverage can help mitigate the financial costs of vaccination; lack of coverage is a frequently cited barrier to delivery of adolescent immunization (27, 91, 99). In the U.S., the cost of vaccination is covered for many girls with private insurance, and is also covered for many low-income girls by public financing (Medicaid and the Vaccines for Children Program or VFC). However, not all women in the recommended age group for vaccination can afford vaccination; not all commercial insurance plans cover all or the full cost of vaccination; and adolescents from low-income families – especially those older than 18 years of age – may not qualify for vaccination under Medicaid or VFC (1, 2). Private insurance coverage and coverage through federal and state programs may partially address cost as a barrier to vaccination; however, there are costs associated with clinic visits and the time spent on obtaining the HPV vaccine (14). One study suggests that to reach optimum vaccine coverage levels, subsidies would need to be offered to cover these additional costs; alternatively, the cost of the quadrivalent vaccine would have to decrease by $55 per dose (14).

Since the ACIP recommendations for HPV vaccination were published (84), there has been a flurry of policy and regulatory activities that could potentially impact uptake of the vaccine. The activities focus on financing HPV vaccination particularly through the Vaccine for Children program, Medicaid and private insurance; legislation regarding mandatory HPV vaccination; and education about HPV vaccination.

In the U.S., HPV vaccine financing requirements have in large part been borne by private health insurance companies, that tend to cover the majority of costs associated with obtaining recommended vaccines for their members. However, not all insurance companies cover all recommended vaccines. To increase coverage, many states have introduced legislation to require private insurance companies to cover the HPV vaccine, but only a handful such as Iowa, Colorado, Illinois, Nevada, New Mexico, Rhode Island, and Texas have enacted such laws. For children 18 years or younger who are eligible for Medicaid and do not have other health insurance, the federally funded VFC program covers the cost of immunizations. Unfortunately, significant numbers of children are under-insured and not eligible for the VFC program. For them, Section 317 of the Public Health Service Act provides funds to states to cover vaccination costs, but funding from this source has not kept pace with the rising cost of vaccines making it difficult for states for cover cost of HPV vaccination for these children and for other uninsured and under-uninsured groups (65). In addition, there are no widespread federal programs to assist with the costs of HPV vaccination for low-income or uninsured women between the ages of 19-26 years who cannot afford to pay for the vaccine. In response, some states such as New Hampshire, South Dakota and Washington, are supplementing federal funds to increase HPV vaccine uptake by providing vaccines at low or no cost.

A policy strategy to increase uptake of vaccines has been to use vaccination mandates, particularly for school entry (67, 111) and immigration. Bills requiring HPV vaccination for school entry have been introduced with much controversy in 28 states and the District of Columbia. In February, 2007, Texas became the first state to enact a school entry mandate by executive order from the governor. The Texas legislature, however, overrode the governor's order and in fact later passed a law to prohibit mandates for HPV vaccination. Also in 2007, Virginia passed a school vaccine requirement but later removed the requirement. The District of Columbia remains the only place in the United States that has enacted and kept a school entry mandate for the HPV vaccine (with an opt-out option).

Some states have taken the approach of using policies to increase educational efforts regarding the HPV vaccine. For example, Iowa, Colorado and North Carolina enacted legislation that requires HPV vaccine education in schools through sex education classes or by providing educational materials to parents. Other states, such as Texas and North Dakota have enacted legislation to require their state department of health to educate the public about the HPV vaccine, so that parents are fully informed about vaccine decisions.

Conceptual Framework/Logic Model for Integrating Clinical, Community and Policy Interventions for Promoting HPV Vaccine Uptake

Figure 1 presents an evidence-based logic model reflecting the existing literature on determinants of HPV vaccination and represents relationships between various factors. This type of conceptual model, described by Bartholomew, et al., (13) and derived from the PRECEDE model (56), provides a framework for organizing the causal factors associated with the health behavior of interest. Additionally, this model allows the depiction of multiple interacting levels of the environment, which often have a profound impact on individual decision-making and behavior.

Figure 1
Logic Model of Factors Influencing HPV Vaccination

The model proposes that willingness or intention to vaccinate one's daughter or oneself (“behavioral factors”) influence HPV vaccination, which in turn leads to a reduction in HPV-related disease. “Environmental factors” (interpersonal, organizational, and community/societal) also influence willingness or intention to vaccinate one's daughter or oneself. Finally, factors influencing behavioral factors and environmental factors are shown in the boxes to the left. The relationships represented in Figure 1 are proposed pathways that are supported by the evidence reviewed above. However, since many of the findings are based on cross-sectional studies and measures of vaccine acceptability rather than actual uptake, it is important to view this model as a proposed framework that may be further supported or modified based on future studies.

Recommendations for Interventions and Future Research

Implications for interventions

A goal of this paper has been to integrate findings from studies that have examined personal, interpersonal, organizational and societal factors that influence HPV uptake to inform a conceptual model (Figure 1) for intervention planning and evaluation. Multi-component intervention approaches that include methods and strategies to effect change at multiple levels are likely to have the greatest impact on HPV vaccination behavior.

Educational interventions and messages for both parents and young women should stress the low rate of serious adverse events associated with vaccination, and emphasize evidence of durable efficacy. Promoting awareness of the high prevalence of HPV infection and the fact that young women are vulnerable to HPV-associated illnesses, including cervical cancer, will also be needed given perceptions of low susceptibility among both women and parents. Given the importance of social and subjective norms in studies both of these groups, it may be useful to develop peer-led interventions (for young women) or educational campaigns that depict vaccination as normative. Specific educational interventions for parents must also stress that vaccination is most effective if administered prior to sexual initiation and should also address concerns about potential adverse effects on adolescent sexual behaviors. Interventions that promote effective communication between parents and their children about sexual health issues may lessen these concerns. Intervention approaches and messages that are effective for low literacy audiences are critical to avoid disparities in vaccine uptake (109). Finally, removing or reducing cost barriers, by providing information about federal vaccine programs that offer free vaccine for families who qualify, and alerting individuals to the potential for insurance coverage by many carriers, would also be an important aspect of interventions.

Providers clearly play an important role in the vaccine decisions of parents and other individuals, and are an important resource in efforts to improve accuracy of risk perceptions, promote and endorse vaccination prior to sexual initiation, and educate parents about issues related to the sexual health of their children. Organizational and provider-level interventions should address factors such as vaccine policies and procedures; knowledge and awareness of HPV vaccines/vaccine guidelines; communication about vaccines; and potential barriers such as vaccine cost (77).

Office- or clinic-based vaccination, school-based vaccination programs, and public health campaigns are some of the methods by which adolescent vaccines may be successfully delivered. Clinic procedures to improve vaccination rates, such as recall and reminder systems, are effective, particularly if these systems are automated. In addition, clinician reminders about vaccination, as well as chart-auditing with feedback to clinicians, can be an effective strategy for changing provider practices (68, 106, 107). School-based programs have been shown to be feasible and acceptable in high-income countries (21). Schools can also provide education about vaccines for students and distribute information to parents.

Ensuring that HPV vaccination is affordable and accessible will be critical to ensure high uptake rates and avoid inequities in vaccination. Reducing costs for the individual via insurance coverage and through state and federal programs will be crucial. More importantly, federal efforts will be needed to negotiate cost reductions for the public health system. Both will likely be complicated, given broader economic pressures. Federal programs such as VFC and funds from Section 317 of the Public Health Service Act will likely need to be augmented by state funds to ensure greater access and equitable delivery of the vaccine.

Policy strategies will also play a critical role in HPV vaccine uptake. While the role of mandates remains controversial, school-entry requirements have been extremely effective in attaining high rates of vaccination for other diseases (8, 90). Mandates may not be politically feasible in the U.S. now, but state legislation that requires private and public insurance coverage for the vaccine, as well as requirements for public education about the vaccine may be useful in addressing some of the personal and organizational barriers noted above.

Future research

The logic model in Figure 1 depicts a broad perspective for considering a number of factors influencing HPV vaccination and helps identify gaps in the evidence. Based on this review, it is evident that additional research is needed to: 1) document HPV vaccination behavior and monitor potential variability across population subgroups; 2) provide stronger evidence of the association between behavioral and/or environmental factors and vaccination behavior, and examine the interrelationships between factors that influence vaccination at various levels; 3) examine the impact of vaccination on sexual behavior and cervical cancer screening; and 4) evaluate the effectiveness of multilevel interventions.

Since the majority of studies on both parental and individual attitudes and beliefs about the HPV vaccine were conducted prior to licensure, studies examining factors related to actual vaccine receipt are needed. Theoretical and empirical evidence suggest a strong link between intention and behavior (41, 42, 43); however, some studies have failed to show this relationship (27). Prospective studies that identify predictors of actual vaccine uptake (that is, receipt of at least one vaccine dose) and completion of the series will provide stronger evidence of the causal relationships between personal and external factors and vaccination. Monitoring to ensure equitable distribution and uptake of the vaccine is also critical.

A better understanding of factors that influence organizational and community/societal predictors of HPV vaccination is needed. Studies that address questions such as why organizational and policy changes take place, who is responsible, and what factors would influence decision-makers to make these changes are all needed to develop interventions that can impact this level of the environment. Moreover, studies that simultaneously examine personal and environmental factors and their interaction are needed to better understand their reciprocal relationships on vaccination.

Research on the impact of vaccination on perceived risk and sexual behaviors is another area of needed study (14). While studies of parental beliefs indicate that some parents are concerned that vaccination may lead to riskier sexual behaviors, studies of other interventions that protect against potential negative consequences of sexual activity do not support this notion (54, 101). Studies that examine the impact of vaccination on sexual behavior are needed to construct evidence-based messages that can address the concern parents express and to design interventions to minimize adverse behavioral responses to vaccination. In addition, since continued Pap test screening is needed for individuals who have been vaccinated studies should examine how vaccination impacts screening behaviors and interventions should emphasize the importance of continued routine screening after HPV vaccination.

Perhaps one of the most significant gaps in the literature exists is in the development and evaluation of interventions designed to increase HPV vaccination. Health communication studies that test various characteristics of vaccine promotion messages including message framing, source, delivery channel, and content are needed (52, 53, 62, 82). Information as to the most effective way to present the vaccine (e.g., as an STI vaccine vs. a cervical cancer vaccine) (62) in order to increase uptake, and whether preferences for information differ between parents and young women, can inform intervention approaches. Additionally, studies that explore the relative efficacy of interventions that utilize an “informed decision-making” approach that aims to inform individuals of the risks, benefits and limitations of vaccination, versus a “persuasion approach” that aims to maximize vaccine uptake without decision support are also needed.

Additional studies are needed to understand the variety, scope and impact of legislative activities at the state and federal level in the United States, and of the driving forces behind policy formation and enactment. Research is also recommended to determine the optimal cost for the vaccine, so that it is affordable enough to ensure that vaccination rates are high enough to achieve herd immunity as well as to reduce the potential inequities in vaccine uptake and cervical cancer. Finally, research in developing countries and among groups at highest risk for HPV-associated disease is needed. Women who are not typically screened for cervical cancer are also likely not to receiving the vaccine for themselves and their daughters. Specific research and intervention approaches are needed to encourage vaccination in these groups so as not to exacerbate existing disparities in HPV-associated diseases.

Summary Points

  1. HPV vaccines are safe and effective; maximizing the public health benefits of HPV vaccines will depend on uptake.
  2. Both personal and external factors influence vaccine acceptability and intent.
  3. Using a multilevel socio-ecological model to organize factors influencing HPV vaccination can help in the design of interventions and guide future research.
  4. Interventions that affect change in parental and personal knowledge and attitudes about the HPV vaccine are needed to increase uptake.
  5. Multilevel interventions impacting personal, interpersonal, organizational and societal change are likely to be the most effective in increasing HPV vaccination uptake.
  6. Future research should focus on evidence of the association between behavioral and/or environmental factors and actual vaccination behavior, examine the interrelationships between factors that influence vaccination at various levels, and evaluate the effectiveness of multilevel interventions.


We thank Karyn Popham, Dolores Proubasta, Jon Kerner, Matthew Kreuter

Research for this publication was supported by the Centers for Disease Control and Prevention (CDC) and the National Cancer Institute (NCI) cooperative agreements for the Cancer Prevention and Control Research Networks (CPCRN) at University of Texas School of Public Health ((1-U48-DP-000057); Harvard School of Public Health/Boston School of Public Health (1-U48-DP000064); University of California at Los Angeles School of Public Health (1U48DP000056: SIP 16-04); and by R01 AI073713 and the Charlotte R. Schmidlapp Award, Fifth-Third Bank, Cincinnati, OH.

Key Terms and Definitions

Quadrivalent HPV vaccine
vaccine that protects against HPV types 6, 11, 16, and 18 (HPV-6/11/16/18)
Bivalent HPV vaccine
vaccine that protects against HPV types 16 and 18 (HPV-16/18)


Human papillomavirus
Centers for Disease Control and Prevention
Advisory Committee on Immunization Practices
World Health Organization
Vaccines for Children Program


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