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HPV vaccine Gardasil 9 now FDA approved for oropharyngeal and other head and neck cancers

by Emily C. Newsom, MD, FACMS

The FDA has recently approved an expanded indication for the HPV vaccine Gardasil 9 (Merk) for the prevention of oropharyngeal and other head and neck cancers caused by HPV types 16, 18, 31, 33, 45, 52 and 58. The approval is based on effectiveness in preventing HPV-related anogenital disease. A confirmatory trial is currently underway.  Oropharyngeal cancer affects men 5 times more than women², which is why it is important for males to be vaccinated.

Gardasil 9 vaccine is indicated for both females and males age 9-45 years old for prevention of HPV-associated lesions of the head and neck and anogenital cancers and precancerous lesions. It is also approved for genital warts caused by HPV types 6 and 11.¹ The vaccine is ideally given at age 9, prior to the onset of sexual activity.  HPV is so common that 80% of people who are sexually active will get HPV at some point in their lives.Gardasil 9 vaccine is indicated for both females and males age 9-45 years old for prevention of HPV-associated lesions of the head and neck and anogenital cancers and precancerous lesions. It is also approved for genital warts caused by HPV types 6 and 11.1 The vaccine is ideally given at age 9, prior to the onset of sexual activity.  HPV is so common that 80% of people who are sexually active will get HPV at some point in their lives.

The Advisory Committee on Immunization Practices (ACIP) recommends HPV vaccination for children and adults aged 9-26.³  For adults aged 27-45 years, the ACIP recommends shared clinical decision for HPV vaccination using the following considerations:

• Most sexually active adults have been exposed to some HPV types, although likely not all 9 HPV types targeted in Gardasil 9.
• Adults in a long-term mutually monogamous sexual partnership are not likely to acquire a new HPV infection.
• At any age, a new sexual partner is a risk factor for acquiring a new HPV infection.
• There is no antibody test to determine HPV immunity.
• HPV vaccines prevent new infections and do not prevent progression of HPV infection to disease, decrease time to clearance of HPV infection, or treat HPV-related disease. 

Insurance coverage may be an issue for adults age 27-45 as well.

The CDC now recommends two doses of HPV vaccine for anyone starting the vaccination series before the 15th birthday. Three doses of HPV are recommended when starting the vaccination series on or after the 15th birthday and for individuals with certain immunocompromising conditions.

The 9-valent Gardasil 9 is currently the only HPV vaccine available in the US.  Previously, a 4-valent and a 2-valent vaccine were available.  The ACIP does recommend completing the series with 9-valent HPV vaccine if the series was started with a different HPV vaccine product. There is no ACIP recommendation for additional 9vHPV doses for persons who previously completed a series of 4vHPV or 2vHPV, and guidance is needed. However, the ACIP does list the following considerations for this specific clinical scenario:

• The majority of all HPV-associated cancers that can be prevented by vaccination are caused by HPV 16 or 18. These HPV types are prevented by all three HPV vaccines: 2vHPV, 4vHPV and 9vHPV.
• The benefit of protection against the five additional types targeted by 9vHPV would be mostly limited to females for prevention of cervical cancers and precancers. This is because only a small percentage of HPV-associated cancers in males is due to the five additional types prevented by 9vHPV.
• Available data show no serious safety concerns in persons who were vaccinated with 9vHPV after having received three doses of 4vHPV.
• Cervical cancer screening is recommended beginning at age 21 years and continuing through age 65 years for both vaccinated and unvaccinated women.

HPV can be associated with cutaneous squamous cell carcinoma (cuSCC), particularly periungal and anogenital cuSCC, and most commonly are associated with HPV types 16 and 18.4 HPV types 16 and 18 possess E6 and E7 proteins that prevent apoptosis and allow for continuous replication of viral DNA by regulating p53 and retinoblastoma, respectively. However, HPV is not transcriptionally active in cSCC; if HPV is involved in pathogenesis, it is likely involved during the induction, not the maintenance, of cSCC.⁴ For staging purposes, HPV is not listed as a high risk feature in AJCC-8 or Brigham and Women’s classification.   However, Mohs surgery is a consideration for HPV-associated cutaneous SCCs as the recurrence rate is higher than that for other cutaneous SCCs, although the rate of metastasis is low.⁵

References

1. Food and Drug Administration. Prescribing information [Package insert]. Gardasil 9 [Human Papillomavirus 9-valent Vaccine, Recombinant], Merck & Co., Inc. Silver Spring, MD https://www.merck.com/product/usa/pi_circulars/g/gardasil_9/gardasil_9_pi.pdf
2. Senkomago V, Henley SJ, Thomas CC, Mix JM, Markowitz LE, Saraiya M. Human Papillomavirus–Attributable Cancers — United States, 2012–2016. MMWR Morb Mortal Wkly Rep 2019;68:724–728. DOI: http://dx.doi.org/10.15585/mmwr.mm6833a3
3. Meites E, Szilagyi PG, Chesson HW, Unger ER, Romero JR, Markowitz LE. Human Papillomavirus Vaccination for Adults: Updated Recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep 2019;68:698–702. DOI: http://dx.doi.org/10.15585/mmwr.mm6832a3
4. Syril Keena T. Que, Fiona O. Zwald, Chrysalyne D. Schmults. Cutaneous squamous cell carcinoma: Incidence, risk factors, diagnosis, and staging. Journal of the American Academy of Dermatology, Volume 78, Issue 2, 2018, Pages 237-247,ISSN 0190-9622. https://doi.org/10.1016/j.jaad.2017.08.059.
5. Alam M, Caldwell JB, Eliezri YD. Human papillomavirus-associated digital squamous cell carcinoma: literature review and report of 21 new cases. J Am Acad Dermatol. 2003 Mar;48(3):385-93. doi: 10.1067/mjd.2003.184. PMID: 12637918.