Introduction

Globally, Human Papillomavirus (HPV) is one of the most highly prevalent sexually transmitted infections (STIs) with an estimated 6 million new infections every year [1]. HPV spreads through sexual contact via areas of the body such as the mouth, genital area, and anus. There is a long latency period before cervical cancer may develop, which sometimes makes carriers asymptomatic and unaware that he or she may be spreading the virus to others [2]. Detection of high risk HPV types should be of high priority because if left untreated, they may eventually lead to cervical cancer – the second leading cause of cancer-related death in women around the world [3]. The distribution and uptake of vaccines to avert HPV infections are crucial steps to prevent the development of cervical and other cancers. There are currently two HPV vaccines available: quadrivalent vaccine (HPV4) and the bivalent vaccine (HPV2). Both have shown to protect against chronic infection from HPV types 16 and 18, the two viral genotypes associated with almost 70 percent of all cervical cancer cases worldwide [4]. However, access to HPV vaccination is unequal across all parts of the world. Minimal access and availability to the vaccines in many developing countries is influenced by the global variation of social and economic factors [5]. Those regions of the world with marginal cancer screening programs, limited access to new vaccines, and overall low health care resources have the highest burden of cervical cancer. Adequate resources to prevent chronic HPV infection are imperative in order to reduce the persistent rates of cervical cancer in these parts of the world. We explore limitations of HPV vaccine access by exploring social and economic differences among developed and developing countries. In addition, we argue that an educational component aimed on HPV at high risk populations is essential and must be implemented in addition to any vaccination programs worldwide.

Global Comparison

The Developed vs. Developing World

Cervical cancer is a disease that affects both developed and developing nations but not at the same level of severity. In Western Europe, the incidence of cervical cancer is only 2.0 for every 100,000 individuals, yet in countries of low and medium income, such as those in South and Central America, cervical cancer continues to be the leading cancer-related death among womenwith an incidence rate of 14.4 percent [6, 7]. Both the World Health Organization and Centers for Disease Control and Prevention recommend vaccinating girls between the ages of 9 to 11 for high-risk HPV types such as 16 and 18 with the hopes of decreasing the acquisition of HPV and the development of cervical cancer for these young girls. Yet, HPV vaccination regimens include three doses within a period of six months, making adherence to the schedule difficult because of the high cost for the complete regimen [8]. One dose of either HPV 2 or HPV 4 is estimated to cost close to 100 US Dollars, which may be equal to more than one month’s salary for a family in countries of low economic resources; and completing the three vaccines necessary for prevention may have a cost as high of $360[9,10]. In developing nations afflicted with high poverty, such as India and Peru, the price for these vaccines limits their availability and accessibility to women that are not among the affluent sector of the population. In addition to the HPV vaccine, cancer screening programs are limited due to high cost, even though they are an essential component to prevent the development of cervical cancer [11]. Additionally, developing countries may have to wait up to a decade for the vaccine to become available to them[12].Costs, which influence the availability of the HPV vaccines and cervical cancer screenings programs, prevent women in developing countries with high poverty rates, like Peru and India, from being able to access these preventative health services [13]. Recent efforts to reduce the burden of cervical cancer in countries with minimal resources have lead to the creation of a low-cost, low-interference HPV testing for cervical cancer screening. With the support of PATH, QIAGEN developed careHPV, a HPV screening test, which provides women with no access to health care services the opportunity to be screened for any signs of HPV which would lead them to the development of cervical cancer [14]. Fig. 1 summarizes some differences between the United States, Peru, and India in regards to socioeconomic indicators, HPV prevalence, and the burden of cervical cancer.

Fig. 1: Comparison of health indicators and HPV-specific information in the US, Peru and India

Peru

Cervical cancer is the leading cause of cancer deaths in women ages 16 to 64 in Peru [2]. With an incidence rate of 34.5 for every 100,000 women, Peru has one of the highest incidence rates of cervical cancer in the world[7] (Fig. 1). The prevalence of HPV is therefore also elevated. A case-control study conducted in Peru showed that 86% of women in the participation group had HPV had type 16, followed by 21% of women who had HPV type 18 [15]. Efforts to control the spread of HPV and reduce the burden of cervical cancer in Peru are limited because of few cervical cancer screening programs and treatment options. An estimated 7.5 percent of women in Peru are carriers of HPV, yet most do not receive cancer screening [16]. Both social and economic factors affect the continuously high prevalence of HPV and development of cervical cancer in Peru.

From 2000 to 2009, Peru allocated 13 percent of its national expenditure to health care, while the United States allotted 24 percent, illustrating financial deficits in Peru for cancer prevention programs [17]. The Peruvian government has not been able to contribute more funding for health programs, which include subsidies for vaccinations and medical treatment to provide individuals who cannot afford to pay for it out of pocket, which happens to be a significant proportion of the population. In Peru, an estimated 31.3% of individuals are below the poverty line compared to the United States where only 15.1% are calculated to be below the poverty line [18]. Those who have the means to pay for the vaccination will do so even if a large portion of the population cannot [19]. Little government support and resources to pay for the high cost of HPV vaccines limit the possibility of reducing the spread of HPV and the development of cervical cancer. It may take years for the HPV vaccine to reach the general population in Peru at an affordable cost [19].

India

With a population of over 1.1 billion people, India shares about one fourth of the global cervical burden [4]. As noted on Fig. 1, the prevalence of HPV in India is estimated to be roughly 6.6percent and HPV type 16 and 18 contribute to over 80% of total cervical cancer cases [16]. In contrast to the U.S. incidence rate of 1.6%, the incidence of cervical cancer in India is 25.9% [3]. Due to socioeconomic constraints, there is no known HPV vaccine available in India.

Due to low availability of health screenings and reproductive health access, developing countries like India suffer from a high prevalence rate of HPV which increases the amount of cervical cancer cases [4]. Low availability to health care resources is a direct effect of a country’s economic resources and investment for decreasing the burden of cervical cancer. Compared to both Peru and the United States, India allocated only 2% of its national expenditures to healthcare[18]. Little government funding and the high costs of the HPV vaccines prevent the implementation of routine vaccination and cancer screening programs for women in India. This affects the sector of the population with the least amount of resources. An estimated 25% of the population in India lives below poverty level compared to 15.1% in the United States [18]. With almost no government money for health care funding, individuals cannot get the HPV vaccine nor can they receive routine screenings to detect cervical cancer.

Recommendations

Primary Target for Vaccination: Young Girls

At an alarming rate, 70% of sexually active individuals will attain one of the HPV genotypes at some point in their lives [23]. Women in early adulthood, namely those under 25 years of age, have the highest rate of infection. The initiation of sexual activity has been found to be on average between the ages of 15-19 among women around the world [24, 26]. Recommendations for the vaccine HPV vaccine specify administering it to an age group that has not yet been exposed to HPV types present in the vaccine therefore; the ideal target age group is sexually naïve without any risk to HPV exposure [25]. Global consensus specifies that young girls starting at 9 to 13 years of age should receive the HPV vaccine since they tend to be the least sexually active age group [4, 6, 25]. Targeting young school-aged girls, as has been done with programs such as PATH, which are seen as essential to the prevention of HPV. Promoting vaccination among younger girls is also seen as being economically beneficial. Programs which have this age group have projected a significant reduction in costs associated with cervical cancer screening, follow-up of abnormal screening, and the diagnosis and treatment of cervical cancer [25]. We should have a better understanding of true cervical cancer prevention when long term data from the vaccine is available.

The Need for Education: Sexual Health and Screening Programs

Even though a target group for the HPV vaccine has already been identified, an educational component must also be included in the global recommendations. The World Health Organization stresses the need for educating both vaccinated children and their parents about the strategies to further reduce the risk of acquiring HPV infection [25]. A survey conducted in India found that the majority of parent surveyed with daughters between the ages 9-16 year were unaware of the existence of HPV. In addition, they believed their daughters were not at risk of contracting the virus simply because of the child’s upbringing and family status [4]. These social implications are important to consider when promoting the HPV vaccine. In order to reduce the negative connotation of the vaccine, it should be promoted as a “cervical cancer prevention” program rather than simply a vaccine against STIs for sexually active individuals [4]. Prevention efforts must include the promotion of routine cervical cancer screening after sexual activity has begun and must provide information on safe sexual practices. If a young girl is vaccinated and develops a false sense of security against contracting HPV, she may neglect to continue receiving proper screening for cervical cancer as well as participate in high-risk sexual activities.

The importance of cervical cancer screening and HPV transmission information must be promoted to all girls between the ages of 15-19 following the start of sexual activity and their previous completion of all three dosages of the HPV vaccination. According to the recommendations by the CDC, women should receive cervical cancer screening at the age of 21 or three years after their first sexual encounter [27]. Thus, young girls must be informed of the importance of cervical cancer screening to detect any signs of cervical cancer. Cancer screening continues to be extremely important; screenings have been associated with a reduction in cervical cancer mortality by up to 80%, which may be more than the reduction provided by HPV vaccine [28]. It is essential then to have routine screening regardless of vaccine receipt to monitor any signs of the development of cervical cancer.

The cervical cancer prevention education program must include education on sexual activity and co-factors that influence the development of cervical cancer. Since HPV is transmitted through sexual contact, health officials will need to stress the importance of continual safe-sex practices [2]. Young girls, usually between the ages of 15-19, who have multiple sexual partners are more likely to have unprotected sex than women in other age groups [29]. Even though the quadrivalent and bivalent vaccines exist, the HPV strands targeted to prevent are types 16 and 18, and types 6 and 11 in the case of HPV4. Thus, there is still a risk of attaining one of the other identified types of HPV that are currently known [4]. Education campaigns that encourage safe sexual activity must be accompanied by vaccination promotion. Current HPV vaccination programs, such as PATH, that make the availability of the vaccine possible to low-income areas around the world, must also prioritize resources to incorporate an educational component. A vaccine does not replace the importance of an emphasis on cervical cancer screening and condom use to prevent HPV transmission. For example, compared to the United States where 79 percent of women were reported to use contraceptives, UNICEF’s report indicates that only 74 percent of women in Peru and 54 percent in India reported using contraceptives [17]. Thus, campaigns that promote safe sexual encounters to prevent the acquisition of HPV and other sexually transmitted diseases are significant. When adding a vaccine into the immunization schedule, health care providers must stress the importance of educating on the importance of screening programs and safe sex practices.

In order to reach out to these young girls, educational programs could be implemented through primary schooling, health-care facilities, and community-based settings [4, 25].It is easier to reach target populations in settings where they are active participants instead of trying to force them out of their environment. PATH’s efforts in Peru and India demonstrate there is an effective relationship between receipt of HPV vaccine and it is an effective strategy to have contact with the vaccinated girls while they are in school. Results have shown that the ease of administering all three dosages to the young girls was high since health care workers could just find them at school. In addition, this has been a cost-effective strategy since they know where to find the girls who they are vaccinating [30]. Therefore, incorporating an educational component to programs already in place consisting of cervical cancer screening and sexual health will be effective if it is done through the primary schooling system. It would be important to incorporate the school system into these efforts in order to reach a large number of the target population.

Special High Risk Populations

Despite the fact that current vaccination programs target young pre-adolescent females ranging from ages 9 through 13, with a maximum age of 26 years, programs to include vaccination of high-risk groups may be important. Even if members of these groups are not within the target group range the immune system continues to respond to the vaccine with high effectiveness as the age of the individuals who receives it increases [31]. One of the primary risk factors associated with the high prevalence rate of HPV infection in females includes having multiple sex partners.Female sex workers (FSW) are not only more likely to have had early exposures to HPV, but also have repetitive exposures through their sexual activities with and without condoms. Specifically in Peru, FSWs have a higher probability than the general population of acquiring a HPV infection due to engagement in high-risk activities with multiple sex partners [32]. In India, oncogenic HPV prevalence was found to be 25 percent in sex workers, higher than the prevalence of the general population, which is 6.6percent [21, 33]. The prevalence of HPV among FSWs in India shows a decreasing trend of HPV prevalence with age: the younger the FSW, the more likely she is to be infected with HPV, which is directly correlated with the probability of developing cervical cancer [32,33]. Given their ability to serve as a bridge population and vector of disease transmission, targeting female sex workers to receive the HPV vaccination as well as education is an important component for a successful intervention program for the general population.

A second target group is men who have sex with men (MSM), a population at risk for developing HPV-related diseases such as anal cancer, penile cancer, and genital warts. Infections caused by high-risk types of HPV have been found to cause 80percent of anal cancer cases [34]. Incidence of anal cancer is highest among MSM who are 20 times more likely than heterosexual men to develop anal cancer [34]. To address this growing problem, researchers have suggested implementing cancer-screening programs for this high-risk population. In addition, vaccination of young adolescent boys before the onset of sexual activity can also prevent HPV-related diseases in all men instead of only MSM [34]. Currently, the quadrivalent vaccine is approved for the prevention of anogenital warts in males [22]. Additionally, the bivalent vaccine has been shown to protect against anal cancers caused by HPV types 16 and 18, which could reduce the prevalence of anal cancer in both men and women, though the CDC currently only recommends the bivalent vaccine for males [35]. It is essential for public health officials to consider both the primary target population, as well as high-risk groups that include FSWs and MSM in order to implementing a successful HPV vaccination program.

Final Thoughts

It is our hope thatone day that all men, women, and children will have equal access to the best available medications and treatments worldwide to reduce global health disparities. Thus, as health professionals it is important to examine inequalities among countries with fewer economic resources in respect to their access to vaccines and medications. As the HPV prevalence endures, it is important to employ programs that could potentially help reduce the infection rate of HPV and the incidence rate of cervical cancer all over the world. By incorporating educational programs to currently established vaccination programs for young girls, a form of prevention against the spread of HPV and development of cervical cancer can be established. Additionally, putting into practice a vaccination schedule for female sex workers (FSWs) and men who have sex with men (MSM) can be useful to control the rate of HPV transmission among these high-risk populations. It is essential for countries with limited resources and high-risk populations to have greater access to vaccinations to reduce the prevalence of HPV and associated diseases.

Limitations

There are a few limiting factors to consider when working on implementing an educational component to the current and future HPV vaccination programs. First, it is essential to consider the cost for vaccination programs that would be additional to the cost of the vaccine itself. Current research on the HPV vaccine is exploring the option of using less than 3 doses – an option that could improve the financial burden of vaccination in developing countries and increase allocations for an educational component [9]. Funding for these vaccination programs in developing countries can stem from community level organizations, international nonprofit organizations (such as PATH), or private organizations (such as careHPV). Funding is one of the biggest barriers for vaccination of developing countries. Other limitations to consider are the social-cultural impacts of sexual education programs in parts of the world where educating young girls about sex is not acceptable. Adjusting the educational component to match the social climate of the given country can prevent and battle current widespread misunderstandings of the vaccine—such as the vaccine causing impotency, a sign of sexual activity, and lack of social status [7]. Therefore, it is important to consider the ambiance of the location where these educational components will be incorporated.