Novel Vaccine Strategies and Factors to Consider in Addressing Health Disparities of HPV Infection and Cervical Cancer Development among Native American Women

Abstract

Cervical cancer is the 4th most common type of cancer in women world-wide. Many factors play a role in cervical cancer development/progression that include genetics, social behaviors, social determinants of health, and even the microbiome. The prevalence of HPV infections and cervical cancer is high and often understudied among Native American communities. While effective HPV vaccines exist, less than 60% of 13- to 17-year-olds in the general population are up to date on their HPV vaccination as of 2020. Vaccination rates are higher among Native American adolescents, approximately 85% for females and 60% for males in the same age group. Unfortunately, the burden of cervical cancer remains high in many Native American populations. In this paper, we will discuss HPV infection, vaccination and the cervicovaginal microbiome with a Native American perspective. We will also provide insight into new strategies for developing novel methods and therapeutics to prevent HPV infections and limit HPV persistence and progression to cervical cancer in all populations.

Keywords: L2 capsid protein; gynecology; self-assembly; vaginal microbiome.

Figure 1

Behavioral, clinical, environmental, social, and immunological factors that may contribute to cervicovaginal microbiome, HPV infection, and progression to cancer. Factors that can impact the microbiome and host that increase the risk of HPV infection and cervical cancer can be influenced by behavioral factors (smoking, age of sexual debut, sexual activity such as use of lubricants and sex toys, contraception, feminine hygiene practices, and alcohol consumption), clinical factors (hormonal status, contraception, vaccination status, and hormonal dysregulation conditions such as obesity), environmental factors (geographic location, stress and trauma, and use of drugs/supplements or antibiotics), social factors (socioeconomic status, race or ethnic background, education level, and access to care), and immunological factors (age, epigenetics, altered immunity, and comorbidities such as cardiovascular disease).

Figure 2

Comparing current L1 HPV vaccines with potential future L2 vaccines consisting of a self-assembling peptide platform. Top section shows an HPV capsid consisting of L1 (purple) and L2 (pink) proteins. The L1 proteins self-assemble into VLPs that are used in current HPV vaccines seen on the left blue side. Positive attributes to the current vaccines include strong and long-lasting antibodies against common HPV types; however, these antibodies are specific to the nine different L1 VLPs used. The green side showcases how a peptide platform vaccine would work with an L2 antigen. The bottom right shows a self-assembling peptide and how many of these peptides can self-assemble with anti-parallel stacking. These β-sheet fibrils present the L2 antigen in a multivalent display. Peptide platforms are highly thermostable compared to their VLP counterpart and the antibodies elicited may be broader, offering more coverage.