Answering Human Papillomavirus vaccine concerns; A matter of science and time

In this paper by Dave Hawkes, Candice Lea, and myself, we addressed some common questions about the HPV vaccine and its use in preventing cancer:

Q1: How do we know the HPV vaccine will prevent cancer?

A1: The first HPV vaccine was registered for use in Australia in 2006. Because of the long lead time from HPV infection to the development of cancer, we are currently unable to definitively measure the success of HPV vaccination in reducing the incidence of cervical, or other HPV linked cancers. However, HPV vaccination has already been shown to reduce both HPV infections and HPV-associated pre-cancerous cervical lesions.

The reason we expect a reduction in the rate of certain cancers is by understanding how the virus works. The HPV virus triggers a series of genetic changes, specifically changes in the genes that regulate additional cancer-causing genes. Over time these cells replicate, leading to pre-cancerous lesions in some cases and cervical cancer in others.
 HPV is associated with 99.7% of cervical cancers and is considered a necessary causative factor of cervical cancer. This is despite the knowledge that not every HPV infection progresses to CIN and then to cancer.

Q2: Why is the vaccine being given to boys as well?

A2: HPV vaccination of boys has two major benefits; firstly, it will reduce the transmission of HPV to women and secondly, HPV infection is associated with a number of cancers which males are susceptible to, such as; cancers of the penis (40% HPV association), cancers of the anus (90% HPV association), mouth (3% HPV association) and throat (12% HPV association).

Q3:The vaccine only targets some types of HPV? What about the others?

A3: The two most commonly used vaccines target types16 and 18 for Cervarix® or types, 6, 11, 16, and 18 for Gardasil®, which is the vaccine commonly used in Australia. Strains 16 and 18 are the most common types linked to cervical cancer, while types 6 and 11 are linked to genital warts.

The vaccine has also been shown to reduce infection with some cancer-associated HPV types that are closely related to those in the vaccines types we vaccinate against.

Q4: How effective is the HPV vaccine?

A4: The vaccine provides immunity for HPV types 16/18 in 95% of people who take the recommended course of doses. The current evidence does not show a reduction in protection (as measured by immunoreactivity) over time.

Q5: Is the vaccine safe?

A5: Adverse events have been reported following HPV vaccination, but the overwhelming majority of these reactions are minor and largely local injection site reactions (e.g. redness, swelling, pain at injection site). These reactions do include other minor self-limiting reactions such as syncope (fainting episodes), headache, and nausea. In addition to our paper, the CDC has a useful summary of minor to moderate reactions of short duration for both types of HPV vaccines and other vaccines. These are consistent with other vaccinations.

Matters of general vaccine safety have been previously covered in-depth in the Australian Academy of Science’s booklet, The Science of Immunisation: questions and answers, and the paper Vaccine Components and Constituents: Responding to Consumer Concerns.

Q6: What about reported deaths from the HPV vaccine?

A6: In 2009, a study investigated 32 deaths attributed to Gardasil® reported by the public on VAERS (Vaccine Adverse Event Reporting System). Of the 32 deaths, there was not enough information to identify the person and investigate the cause of death in 12 cases. The cause of the remaining 20 deaths were: 2 due to diabetes, 3 due to pulmonary embolism, 6 were cardiac-related, 2 were idiopathic seizure disorders, 4 were unexplained, 1 was due to juvenile amyotrophic lateral sclerosis, 1 case of meningoencephalitis (inflammation of the brain and surrounding membrane), and the final death was related to prescription drug abuse. The authors concluded that statistically these results were not significantly different from what you would expect from a similar sized un-vaccinated population.

For references and more details please refer to the paper. I appreciate the work of my co-authors on both the paper itself and this blog.

6 thoughts on “Answering Human Papillomavirus vaccine concerns; A matter of science and time

  1. A2: HPV vaccination of boys has two major benefits; firstly, it will reduce the transmission of HPV to women and secondly, HPV infection is associated with a number of cancers which males are susceptible to, such as; cancers of the penis (40% HPV association), cancers of the anus (90% HPV association), mouth (3% HPV association) and throat (12% HPV association).

    What does “association” mean in this context? Do they think 90% of anal cancers are caused by HPV and therefore if all men were immunised that the anal cancer rate would drop by 90%, or something else? It sounds like you are trying to avoid saying the word “causes” but I’m not sure what the alternative explanation might be…

    1. With cervical cancer there’s solid evidence that HPV is the root cause of most; i.e. in only ~0.3% of cases does it occur in the absence of HPV. There is the statistical pattern as well as an understanding of how it triggers the development of CIN evidence. For the other types there are strong correlations:
      http://onlinelibrary.wiley.com/doi/10.1002/cncr.23758/full
      but I’d have to check tomorrow (I need sleep now) as to the state of research in understanding the causal mechanisms there.

    2. This paper: http://www.sciencedirect.com/science/article/pii/S0264410X06007328 talks about different tissue types and why the rates for non-cervical HPV-associated cancers are lower. These two papers: http://genesdev.cshlp.org/content/14/23/3065.short and http://www.pnas.org/content/109/23/E1473.full.pdf+html talk about the role of HPV in skin tumours; the latter talks about the role of “E6 proteins of
      high-risk HPVs of the α-genus such as HPV16 and HPV18” in mediating both p53 (a tumour suppressor gene, since it plays a critical role in the cell cycle) and the Notch signalling pathway (responsible for cellular differentiation). Both cell cycle and cell differentiation pathways are common to tumours, so it seems fair to name HPV as a cause of these other cancers, noting the lower rate due to differences in cell types (as mediated by different signalling in the cells).

      1. Thank you for the very thorough replies!! Some of it is beyond my understanding but it’s great to know the information is out there.

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