HPV vaccines? Still needed

Commentary


HPV vaccines? Still needed


L.Z.G. Touyz, BDS MSc(Dent) MDent (PerioandOralMed)*

doi: http://dx.doi.org/10.3747/co.23.3034

The human papilloma virus (hpv) was at one time deemed benign, with few variants13. Further research revealed 150 serologically identifiable varieties, some benign, but many having oncogenic genes4. Vaccines against some of the latter varieties are Gardasil (Merck, Kenilworth, NJ, U.S.A.) and Cervarix (GlaxoSmithKline, Brentford, U.K.), introduced and recommended for girls before their sexual debut5. Some theological leaders were against vaccination, believing that vaccination leads to promiscuity6. To reduce residual host infection pools, inoculation advice eventually included boys7. Most vaccines successfully impart life-long immunity. Consequently, the earlier the vaccination, the longer and stronger the likelihood of preventing hpv morbidity.

Protection and New Vaccine

Anamnestic responses to viral antigens rapidly boost immunity and prevent disease recrudescence810. Early immunity to hpv is derived from 4 hpv varieties911, and the available hpv vaccines have been successfully used in national vaccination campaigns10. Cervarix protects against hpv-16 and hpv-18; Gardasil, a quadrivalent vaccine, protects against hpv-16, hpv-18, hpv-6, and hpv-11. The additional hpvs (6 and 11) addressed by the Gardasil formulation are causally related to genital condylomata and recurrent respiratory papillomatosis. Other hpvs involved in oncogenesis are hpv-31, hpv-33, hpv-45, hpv-52, and hpv-58.

Antibody induction is rarely complete with a single administration, and small significant groups fail to respond adequately, needing triple inoculation to reach efficacy911. Moreover, the existing protection from early vaccines has limits, and a new broader-based hpv vaccine called V503 (with activity against 9 hpv varieties) was therefore developed. In 2014, the vaccine developer, Merck, made a Biologics License Application for registration of the product13, which is now under review by the U.S. Food and Drug Administration.

DISCUSSION

The causes of many cancers have been defined. For example, asbestos induces mesothelioma, radiation induces neoplasias, aniline dyes cause urogenital carcinogenesis, nitrosamines precipitate oncogenesis in the gut, petrochemicals act as carcinogens, genes (BRCA, for instance) predispose carriers to certain types of cancer, tobacco generates lung-cancer, and alcohol stimulates neoplastic change14.

Surgery, chemotherapy, and radiation remain the main therapies for established cancer, but they have limited success, with significant morbidity and mortality. Despite the definition of many cancer causes, absolute cures remain stubbornly obscure. Prophylaxis remains the most desirable approach, and for cause-defined cancers, prevention with immunity is successful. High-levels of anti–hpv-16 and -18 antibodies persist for up to 7 years, and boosters are recommended. The hpv vaccinations stimulate immunomodulation and contribute to the prevention and lowered prevalence of hpv-positive head-and-neck squamous cell carcinomas and urogenital cancers. Accordingly, vaccination is now advised for all boys and girls before their sexual debut1517. Transmission of hpv can occur during sexual activity or orogenital contact, and even during social kissing or inhalation of spray from sneezes or coughs by hpv carriers18,19. After barrier methods of contraception diminished in the mid-1950s (yielding to major use of contraceptive hormone pills), sexual behaviors and mores changed, and hpv, together with other sexually transmitted infections, became more prevalent.

CONCLUDING REMARKS

Vaccination protection lasts decades and takes a long time to wane9,10. Human papilloma viruses are implicated in cancers other than anogenital neoplasias2022. Vaccination against hpv should be considered essential for all and should become part of the battery of inoculations received in the first decade of life12. Without hpv vaccination, a hpv pandemic is predicted, and use of broad-based vaccines is desirable to optimize hpv prophylaxis23,24. Clinical tests to detect hpv infection are available, and vaccines will protect against hpv morbidity25. The hpv oncogenic protein p53 can be detected during histopathology examination26, and a search for proteins to moderate protein p53 is needed. Because of the proven immune response, all adults who are not inoculated against hpv, who are sexually active, and who face the probability of more than one sexual partner, are well advised also to be vaccinated against hpv. Further research into the clinical management of hpv is needed.

The global cancer incidence is 14 million new cases annually, with a resultant mortality of 8 million individuals. Prophylaxis remains the main mission. In health care, anamnestic or freshly acquired immunity is used to prevent cancers from returning once patients are in remission25. Traditional vaccines are given to healthy patients to induce immunity. ImMucin (Vaxil Israel, Rehovot, Israel) is given to people who are already sick, and yet it behaves like a drug with biologic effects, acting like a cross between a drug and a vaccine as a two-pronged hybrid therapy. Targeting viruses predisposing to cancer is what vaccines can accomplish; they also create immunity against viruses implicated in oncogenesis. Vaxil Israel claims that their immunity works against mutated cells with initial neo-plastic changes, consequently lowering the incidence of early cancers without affecting healthy cells. Vaxil Israel reports success with multiple myeloma and has tried the same approach on other cancers25.

CONFLICT OF INTEREST DISCLOSURES

I have read and understood Current Oncology’s policy on disclosing conflicts of interest, and I declare that I have none.

AUTHOR AFFILIATIONS

*Faculty of Dentistry, McGill University, Montreal, QC..

REFERENCES

1. Jensen AB, Link CC, Lancaster WD. Section ii. Papilliomavirus etiology of oral cavity papillomas. In: Hooks JJ, Jordan GW, eds. Viral Infections in Oral Medicine. Oxford, U.K.: Elsevier Science and Technology; 1982: 132–46.

2. SV40-based gene delivery vectors [in Ch. 15, Polyomaviruses]. In: Norkin LC. Virology: Molecular Biology and Pathogenesis. Washington, DC: ASM Press; 2010: 419–43.

3. Lajer CB, von Buchwald C. The role of human papillomavirus in head and neck cancer. APMIS 2010;118:510–19.
cross-ref  pubmed  

4. Touyz LZG. Human papilloma virus (hpv)—a biological and clinical appraisal: 2013. Science Postprint 2013;1:e00001.
cross-ref  

5. Forman D, de Martel C, Lacey CJ, et al. Global burden of human papillomavirus and related diseases. Vaccine 2012;30(suppl 5):F12–23.
cross-ref  pubmed  

6. Touyz SJJ, Touyz LZG. The kiss of death: hpv rejected by religion. Curr Oncol 2013;20:e52–3.
pubmed  pmc  

7. Touyz LZG. Human papilloma virus inoculation: why only girls? Curr Oncol 2009;16:2.
cross-ref  pubmed  pmc  

8. Crosignani P, De Stefani A, Fara GM, et al. Towards the eradication of hpv infection through universal specific vaccination. BMC Public Health 2013;13:642.
cross-ref  

9. Schiller JT, Castellsagué X, Garland SM. A review of clinical trials of human papillomavirus prophylactic vaccines. Vaccine 2012;30(suppl 5):F123–38.
cross-ref  pubmed  pmc  

10. Malagón T, Drolet M, Boily MC, et al. Cross-protective efficacy of two human papillomavirus vaccines: a systematic review and meta-analysis. Lancet Infect Dis 2012;12:781–9.
cross-ref  pubmed  

11. Safaeian M, Porras C, Pan Y, et al. on behalf of the cvt group. Durable antibody responses following one dose of the bivalent human papillomavirus L1 virus-like particle vaccine in the Costa Rica Vaccine Trial. Cancer Prev Res (Phila) 2016;6:1242–50.
cross-ref  

12. Liu X, Feng A, Cui Y, Tobe RG. Prevention of human papillomavirus (hpv) infection and cervical cancer in China: how does hpv vaccination bring about benefits to Chinese women? Biosci Trends 2013;7:159–67.
pubmed  

13. Merck and Co. FDA Accepts for Review Merck’s Biologics License Application for V503, Investigational 9-Valent Human Papillomavirus Vaccine [press release]. Whitehouse Station, NJ: Merck Co.; 2014. [Available online at: http://www.mercknewsroom.com/news-release/research-and-development-news/fda-accepts-review-mercks-biologics-license-application-v; cited 14 June 2016]

14. American Cancer Society (acs). What causes cancer? [Web page]. Atlanta, GA: acs; 2016. [Available online at: http://www.cancer.org/cancer/cancercauses; cited 25 October 2015]

15. Zhao FH, Lewkowitz AK, Hu SY, et al. Prevalence of human papillomavirus and cervical intraepithelial neoplasia in China: a pooled analysis of 17 population-based studies. Int J Cancer 2012;131:2929–38.
cross-ref  pubmed  pmc  

16. Li J, Huang R, Schmidt JE, Qiao YL. Epidemiological features of human papillomavirus (hpv) infection among women living in Mainland China. Asian Pac J Cancer Prev 2013;14:4015–23.
cross-ref  

17. Syrjänen S. Current concepts on human papilloma virus infections in children. APMIS 2010;118:494–509.
cross-ref  

18. Touyz LZG. Lips, kissing and oral implications. Jnl Aesthetic Dentistry 2009;:29–34.

19. Chaturvedi AK, Engels EA, Pfeiffer RM, et al. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol 2011;29:4294–301.
cross-ref  pubmed  pmc  

20. Nasman A, Attner P, Hammerstedt L, et al. Incidence of human papilloma virus (hpv) positive tonsillar carcinoma in Stockholm, Sweden: an epidemic of viral-induced carcinoma? Int J Cancer 2009;125:362–6.
cross-ref  

21. Heng B, Glenn WK, Ye Y, et al. Human papilloma virus is associated with breast cancer. Br J Cancer 2009;101:1345–50.
cross-ref  pubmed  pmc  

22. Bender E. Developing world: global warning. Sci Am 2014;311:S18–19. [Republished as: Bender E. Developing world: global warning. Nature 2014;509:S64–5]
cross-ref  pubmed  

23. Pashley NR. Can mumps vaccine induce remission in recurrent respiratory papilloma? Arch Otolaryngol Head Neck Surg 2002;128:783–6.
cross-ref  pubmed  

24. Massad LS, Einstein MH, Huh WK, et al. on behalf of the 2012 asccp Consensus Guidelines Conference. 2012 Updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors. Obstet Gynecol 2013;121:829–46.
cross-ref  pubmed  

25. Neff J. New Israeli Cancer Vaccine Triggers Response in 90% of Cancer Types [Web article]. Herzliya, Israel: NoCamels. com; 2015. [Available at: http://nocamels.com/2015/01/newvaccine-for-cancer/; 14 June 2016]

26. Immunological memory [in Ch. 4, Host defenses and viral counter measures] and T antigens and neoplasia [in Ch. 15, Polyomaviruses]. In: Norkin LC, ed. Virology: Molecular Biology and Pathogenesis. Washington, DC: ASM Press; 2010: 136–7;401–5.


Correspondence to: Louis Z.G. Touyz, McGill University, 3640 University Street, Montreal, Quebec H3Y 2B2. E-mail: louis.touyz@mcgill.ca

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Current Oncology, VOLUME 23, NUMBER 4, August 2016








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