Vaccine Strategies for Human Papillomavirus-Associated Head and Neck Cancers

The rising incidence of oropharyngeal squamous cell cancers (OPSCC) in the United States is largely attributed to HPV. Prophylactic HPV vaccines have demonstrated effectiveness against oral infection of HPV 16 and HPV 18. We review the global epidemiology and biology of HPV-related cancers as well as the development of HPV vaccines and their use worldwide. We also review the various strategies and challenges in development of therapeutic HPV vaccines.

Human Papillomavirus Vaccine Efficacy and Effectiveness against Cancer

Human papillomavirus (HPV) is the most common sexually transmitted infection, with 15 HPV types related to cervical, anal, oropharyngeal, penile, vulvar, and vaginal cancers. However, cervical cancer remains one of the most common cancers in women, especially in developing countries. Three HPV vaccines have been licensed: bivalent (Cervarix, GSK, Rixensart, Belgium), quadrivalent (Merck, Sharp & Dome (Merck & Co, Whitehouse Station, NJ, USA)), and nonavalent (Merck, Sharp & Dome (Merck & Co, Whitehouse Station, NJ, USA)). The current HPV vaccine recommendations apply to 9 years old and above through the age of 26 years and adults aged 27–45 years who might be at risk of new HPV infection and benefit from vaccination. The primary target population for HPV vaccination recommended by the WHO is girls aged 9–14 years, prior to their becoming sexually active, to undergo a two-dose schedule and girls ≥ 15 years of age, to undergo a three-dose schedule. Safety data for HPV vaccines have indicated that they are safe. The most common adverse side-effect was local symptoms. HPV vaccines are highly immunogenic. The efficacy and effectiveness of vaccines has been remarkably high among young women who were HPV seronegative before vaccination. Vaccine efficacy was lower among women regardless of HPV DNA when vaccinated and among adult women. Comparisons of the efficacy of bivalent, quadrivalent, and nonavalent vaccines against HPV 16/18 showed that they are similar. However, the nonavalent vaccine can provide additional protection against HPV 31/33/45/52/58. In a real-world setting, the notable decrease of HPV 6/11/16/18 among vaccinated women compared with unvaccinated women shows the vaccine to be highly effective. Moreover, the direct effect of the nonavalent vaccine with the cross-protection of bivalent and quadrivalent vaccines results in the reduction of HPV 6/11/16/18/31/33/45/52/58. HPV vaccination has been shown to provide herd protection as well. Two-dose HPV vaccine schedules showed no difference in seroconversion from three-dose schedules. However, the use of a single-dose HPV vaccination schedule remains controversial. For males, the quadrivalent HPV vaccine possibly reduces the incidence of external genital lesions and persistent infection with HPV 6/11/16/18. Evidence regarding the efficacy and risk of HPV vaccination and HIV infection remains limited. HPV vaccination has been shown to be highly effective against oral HPV type 16/18 infection, with a significant percentage of participants developing IgG antibodies in the oral fluid post vaccination. However, the vaccines’ effectiveness in reducing the incidence of and mortality rates from HPV-related head and neck cancers should be observed in the long term. In anal infections and anal intraepithelial neoplasia, the vaccines demonstrate high efficacy. While HPV vaccines are very effective, screening for related cancers, as per guidelines, is still recommended.

Designing of DNA Vaccine Based on a Secretory Form of Major Capsid Protein of Human Papillomavirus Type 18

More than 99% of cervical cancers are associated with human papillomaviruses (HPVs) worldwide. Current HPV vaccines are safe, highly immunogenic, with effective immunity against specific HPV types. However, DNA vaccines are a new appealing platform which can be considered for designing the HPV vaccines. This study aimed to construct a recombinant eukaryotic expression plasmid containing L1 of HPV-18, tissue plasminogen activators (tPA), and pan HLA DR-binding epitope (PADRE) genes into the pVAX1 vector. The L1, tPA, and PADRE genes were amplified in a thermocycler. The polymerase chain reaction (PCR) products were cloned and insertion of the genes was confirmed using colony PCR, restriction enzymes analysis, and sequencing methods. Indirect immunofluorescence, RT-PCR, and western blot assays were applied to identify the target gene in HEK-293 cells. Total IgG and its isotypes in immunized mice were measured by enzyme-linked immunosorbent assay technique. Western blot analysis showed a protein band of about 67.5 kDa in supernatant and cell lysate of transfected cells. The results of mice immunization with different constructs (group 1: the pVAX-L1, group 2: pVAX-tPA-PADRE-L1, group 3: pVAX1, and group 4: PBS as controls) indicated that the pVAX1-tPA-PADRE-L1 construct induced a significantly higher level of total IgG than pVAX1-L1 (p=0.003). In conclusion, pVAX1-tPA-PADRE-L1 recombinant plasmid is a highly immunogenic construct and suggests as a promising candidate for vaccine development against HPV type 18 in low-middle-income countries.

Designing a Pro-Equity HPV Vaccine Delivery Program for Girls Who Have Dropped Out of School: Community Perspectives From Uttar Pradesh, India

India experiences a substantial burden of cervical cancer and accounts for nearly one third of cervical cancer deaths worldwide. While human papillomavirus (HPV) vaccines have been introduced subnationally in some states, HPV has not yet been rolled out nationally. Given the target age group, schools are the most common delivery channel for HPV vaccines, but this fails to account for local girls who never attended or no longer attend school. We conducted a qualitative, design-informed, community-based study conducted in Uttar Pradesh, India. We assessed facilitators and barriers among out-of-school girls and proposed program characteristics to inform the design of pro-equity HPV vaccine delivery programs for out-of-school girls. Programs should improve parental knowledge of the risk of cervical cancer, engage vaccinated girls as vaccine champions, utilize varied media options for low-literacy populations, and ensure that HPV vaccine services are accessible and flexible to accommodate out-of-school girls. In areas with poor or irregular school attendance among adolescent girls, HPV vaccine coverage will remain suboptimal until programs can effectively address their needs and reach this priority population. Our findings present a meaningful opportunity for program planners to purposefully design HPV vaccination programs according to these parameters, rather than modifying existing programs to include HPV vaccine. Adolescent girls, their parents, and other community members should be involved in program design to ensure that the program can effectively meet the needs of adolescent girls who are not in school.

Impact of Web-Based Health Education on HPV Vaccination Uptake Among College Girl Students in Western and Northern China: A Follow-Up Study

Objective: To investigate the knowledge of human papillomavirus (HPV) and HPV vaccines, HPV vaccination uptake, and vaccination willingness among female college students, and to explore the effect of a web-based educational intervention, immediately and at one month later, on HPV knowledge, vaccine acceptability and uptake among female college students in Western and Northern China. Methods: A web-based interventional follow-up study was conducted at two universities in Western and Northern China between February and April 2020. Female freshmen were required to complete an online questionnaire, and then eligible students were randomized into intervention and control group. Students in the intervention group received 7-days of web-based health education regarding HPV and HPV vaccines, while the control group received educational materials unrelated to HPV prevention. All students were asked to complete post-intervention questionnaire to assess their awareness, uptake, and willingness regarding HPV vaccination at a 7 days and 30 days interval, respectively. Differences between intervention and control groups were compared using the Chi-square test. Multivariable logistic regression was used to analyze the influencing factors of vaccination intentions. Results: A total of 967 participants were included in this study. Prior to the intervention, 63.8%, 66.3%, and 60.8% of students had heard of HPV, HPV-related diseases, and HPV vaccines, respectively. However, only 2.2% of students had reported to have been vaccinated, and 33.0% were willing to be vaccinated against HPV. After 7-days education, students in the intervention group had higher awareness and willingness of HPV vaccines than those in the control group. Major reasons that college female students do not accept HPV vaccines were the high cost (57.7%) and concerns about the adverse events (56.0%). School location, education background of parents, history of counseling about HPV vaccines, history of sexual behavior, and having heard of HPV vaccines are influencing factors on willingness to be vaccinated. Conclusion: The female college students’ HPV vaccination uptake is insufficient, and they have minimal detailed knowledge about HPV and its vaccines. Web-based health education on HPV vaccines is an easy, feasible, and effective way to improve the awareness and acceptance of HPV vaccination among female college students, but it has limited effect on improving HPV vaccination uptake.

Survey on Knowledge and Awareness about Human Papilloma Virus and Cervical Cancer in Parents of School-Going Children

Human papilloma virus lesions are known to cause cervical cancer in persons infected by the virus. The incubation time between an oncogenic HPV infection and cervical cancer is 10-15 years hence preventive measures should be taken in adolescent age. HPV vaccines (Cervarix and Gardasil) reduce the risk of cancerous and precancerous lesion by more than 95%. These vaccines are to be admitted to young children before their sexual debut (11-12 years), since deemed as legal minors, parental consent is required for the administration of the virus. Parental knowledge about cervical cancer and HPV infections plays a vital role in their awareness about the presence of HPV vaccines and their willingness to get their child vaccinated against the same. The study consisted of a pre-validated questionnaire posed before the parents to know their knowledge and awareness regarding cervical cancer, human papilloma virus and sexual health. Key words: Cervical cancer, Human Papilloma Virus, knowledge, awareness, school children, cancer.