HPV Vaccines Continue to be Found Necessary and Effective

A recent review article published in the Journal of Infection on the family of human papillomaviruses (HPVs) and the vaccines developed to fight HPV infections provides ample evidence for the necessity of such vaccines, as well as their effectiveness.¹ The review focuses on the biology of HPVs, their associated burdens, and the clinical data available on HPV vaccine efficacy.

In the review, Margaret Stanley, PhD, BSc, OBE, FRCOG, FMedSci, the Professor and Director of the Department of Pathology at the University of Cambridge, in the United Kingdom, addresses topics including the various types of HPVs, their relationships with different types of cancers, and the three currently US Food and Drug Administration (FDA)-approved prophylactic HPV vaccines. The discussion on the HPV vaccines covers their chemical nature, approval history, and appropriate timing of administration, as well as their impact and induced immune responses. The review concludes with a discussion of the challenges that remain despite advancements made against HPV infections.

In a brief discussion of the family of HPVs, Dr. Stanley explains how the more than 170 types are classified and numbered, as well as which tissue types they are most likely to infect (cutaneous and mucosal squamous epithelia). This discussion is followed by a more expansive discussion of the clinical burden associated with the subset of HPVs regarded as oncogenic. HPV 16 and 18, in particular, are highlighted due to their level of association with cervical cancer. Additionally, HPV 16 has been implicated as the predominant type of HPV in the proportion of cases of carcinoma of the penis, vulva, vagina, anus, and oropharynx attributable to HPV. Dr. Stanley notes that an estimated 5.2% of all cancers worldwide involve HPV infection, making HPV-associated diseases a significant global health problem. This burden is increased when genital warts are factored in, as some of the mucosal HPVs rarely associated with cancers, types 6 and 11 to be specific, are considered to be responsible for this disease. Because genital warts are the most common viral sexually transmitted infection, they represent a very large portion of the overall HPV-associated disease burden and currently lack an adequate treatment option.

The majority of Dr. Stanley’s review is devoted to descriptions of the three FDA-approved HPV-directed vaccines, Cervarix (GlaxoSmithKline Biologicals), Gardasil (MSD Merck), and Gardasil9 (MSD Merck). Dr. Stanley reviews the number and type of HPVs intended to be targeted, the indicated patient age ranges, and approval month and year for each. She notes that all of the vaccines have been proven highly effective (>90%) in large, randomized, placebo controlled, double blind phase III trials in women in the indicated age ranges. Additionally, several real-world examples demonstrating the advantages associated with the use of HPV vaccines are provided to highlight their positive global impact.

Regarding the challenges that remain for the future of HPV vaccines, Dr. Stanley stated, "The focus of discussions about the current vaccines now is no longer about efficacy but rather about implementation, access and affordability." One of the challenges cited in the review article was the need for better adherence to the full 3-dose regimen in school-based immunization programs, which have not been successful in general, and have shown large variations in vaccination coverage. Additionally, it remains unknown whether recently recommended changes from a 3- to a 2-dose regimen will impact vaccine effectiveness for either infection or disease, or duration of protection.

An additional challenge noted by Dr. Stanley involves the current female-only vaccination policies adopted by some. This approach voids any potential for herd immunity, as heterosexual men are not immune and remain susceptible to infection through sexual contact with non-immunized or infected women. Men who have sex with men are afforded absolutely no protection through such a strategy, despite the fact that HPV genoprevalence is known to be high in this population. Immunization of boys would be required to provide true herd immunity, regardless of their sexual preferences. Recommendations for the administration of HPV vaccines in men are currently rare since such policies are not seen as cost-effective. However, Dr. Stanley posits that this opinion may change if evidence emerges regarding the efficacy of single-dose administration.

William Perlman, PhD, CMPP is a former research scientist currently working as a medical/scientific content development specialist. He earned his BA in Psychology from Johns Hopkins University, his PhD in Neuroscience at UCLA, and completed three years of postdoctoral fellowship in the Neuropathology Section of the Clinical Brain Disorders Branch of the National Institute of Mental Health.

References

1. Stanley M/ Preventing cervical cancer and genital warts: How much protection is enough for HPV vaccines?, J Infect. 2016 May 19. pii: S0163-4453(16)30045-7. doi: 10.1016/j.jinf.2016.04.018. [Epub ahead of print].
2. CDC. Antibiotic Resistant Threats in the United States 2013. Available at: www.cdc.gov/drugresistance/pdf/ar-threats-2013-508.pdf. Accessed May 27, 2016.
3. Lessa FC, Mu Y, Bamberg WM, et al. Burden of Clostridium difficile infection in the United States. N Engl J Med 2015;372:825—34.