Elsevier

Antiviral Research

Volume 130, June 2016, Pages 101-109
Antiviral Research

Review
Gardasil-9: A global survey of projected efficacy

https://doi.org/10.1016/j.antiviral.2016.03.016Get rights and content

Highlights

  • The prevalence and distribution of HPV types worldwide differ from one geographical region to another.

  • HPV-infected HIV/AIDS patients progress to invasive cervical cancer 6–15 years earlier than non-HIV patients.

  • Gardasil-9 will protect against HPV types associated with 90% of cervical cancer cases, worldwide.

  • Antibody titers of Gardasil-9 for HPV31/33/45/52/58 in quadrivalent Gardasil recipients are <64% that of seronegative group.

  • Gardasil-9 has not yet been recommended to people who have completed 3 doses of Gardasil or Cervarix vaccines.

Abstract

Human papillomaviruses (HPVs) are the causative agents of human neoplasias such as warts and cancers. There are ∼19 HPV types associated with cancers, which has made it very challenging for first generation HPV vaccines to offer complete protection against all cancer-causing HPV types. Recently, a second generation HPV vaccine, Gardasil-9, has been approved to protect against more HPV types. Worldwide, Gardasil-9 will protect against HPV types associated with ∼90% of cervical cancer case in women and 80–95% of other HPV-associated anogenital cancers in both men and women. However, due to variation in HPV-type specific prevalence and distribution, the vaccine will offer different percentages of protection in different geographical regions; Gardasil-9 will offer protection against HPV types associated with ∼87.7% of cervical cancers in Asia, 91.7% in Africa, 92% in North America, 90.9% in Europe, 89.5% in Latin America & the Caribbean, and 86.5% in Australia. Because of this, Pap smear screening and testing for HPV types not included in Gardasil-9 will need to continue, especially in HIV/AIDS patients. In order to achieve complete protection against all HPV types that cause cervical cancer, a third-generation HPV vaccine is needed.

Section snippets

HPV, transmission and diseases

Human papillomaviruses (HPVs) are non-enveloped viruses with a double-stranded circular DNA genome. The genome is enclosed in an icosahedral capsid, which is made up of two proteins: the major capsid protein (L1) and the minor capsid protein (L2). HPVs infect epithelial cells in the skin and mucosal surfaces (de Villiers et al., 2004). More than 202 different HPV types have been identified up to date and approximately 42 of these HPV types, known as mucosal or genital types, are transmitted

Geographical distribution

HPV16 is the most prevalent HPV type worldwide. The other thirteen most common high-risk HPV types (18, 31, 33, 35, 39, 45, 51–52, 56, 58, 59, 66, 68) have also been detected worldwide but their prevalence and distribution differ from one geographical region to another and even between cervical cytology types; for instance, women with normal cervical cytology have different HPV prevalence and distribution compared to women with cervical cancer cytology (Munoz et al., 2004, de Sanjose et al.,

HPV infection in the context of HIV or AIDS

Human immunodeficiency virus (HIV) is a retrovirus that infects cells of the immune system (CD4 T cells, dendritic cells, macrophages) causing a decline in CD4 cells, immune dysfunction and subsequently acquired immunodeficiency syndrome (AIDS) (Weiss, 1993, Maartens et al., 2014, Doitsh et al., 2014, Harman et al., 2015). HIV has killed more than 39 million people worldwide and there are currently 35.3 million people living with the disease. About 70% of AIDS patients live in Sub-Saharan

HPV and HPV-associated cancers in smokers

Like HIV, smoking has been shown to adversely affect the immune system, thus contributing to HPV infection and cancer progression. Cigarette smoke contains chemicals (tar, carbon monoxide and carbon dioxide, etc.), which impair immune cell functions and reduce cytokine production, hence decreasing the ability of the body to fight infections (Mehta et al., 2008). This has been observed with HPV infections, with smokers having a higher risk of persistent HPV infection and a higher risk of

Vaccines against HPV infections

Three prophylactic vaccines, Cervarix, Gardasil (quadrivalent HPV) and Gardasil-9 (nonavalent HPV), have been approved by the Food and Drug Administration (FDA) in the United States to protect against HPV infections (Tumban et al., 2015). These vaccines are composed of virus-like particles (VLPs) derived from the major capsid protein (L1) of HPV. The vaccines are highly immunogenic, but because they are derived from L1 proteins, which are not conserved among HPV types, they protect mostly

Challenges associated with Gardasil-9 and first-generation L1 HPV vaccines

Among the three HPV vaccines, Gardasil-9 is the only HPV vaccine that protects against five additional high-risk HPV types (HPV31, 33, 45, 52, and 58) associated with cervical, vulvar, vaginal, anal, and penile diseases. The geometric mean antibody titers for these 5 additional HPV types in a seronegative HPV population range from 272.2 to 1894.7 milli-Merck Units/ml (units used by the manufacturer to report their Competitive Luminex Immunoassay, cLIA, data). However, the geometric mean

Prospects for the future

Although Gardasil-9 has set a very high efficacy bar for prophylactic vaccines against HPV infections, the following limitations against HPV vaccines still exist:

  • i)

    A number of high-risk HPV types (e.g.HPV51, 35, 56, 53, 59) associated with ∼10% of cervical cancer cases are not protected by current vaccines. This is especially concerning for the 35.3 million people worldwide with compromised immune systems due to HIV infection/AIDS who have a higher risk of developing cancers from HPV infections.

Financial interest and conflict of interest disclosures

The authors were supported by a start-up fund from Michigan Technological University. Ebenezer Tumban is a co-inventor of L2 bacteriophage virus-like particles-related patent applications licensed to Agilvax Biotech by the University of New Mexico. Interactions with Agilvax Biotech are managed by the University of New Mexico in accordance with its conflict of interest policies.

Acknowledgment

We would like to thank Drs. Kathryn Frietze and Bryce Chackerian (University of New Mexico School of Medicine) for reading the review and for their critical comments and suggestions.

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