Cancer of the throat, or pharynx as it’s known in medical spheres, is a relatively rare cancer with around 6,800 new diagnoses in the UK each year and 2,100 deaths.
Apart from our biggest nemesis – aging – the main risk factors for throat cancer are tobacco and alcohol consumption, which are linked to 65% and 30% of the cases, respectively. However, in recent years an infection has been held responsible for the disease developing in younger adults.
Human papilloma virus or HPV, commonly associated with cervical cancer, is linked to what is now the majority of cases of throat cancer worldwide. Many people became aware of this link when Michael Douglas’s cancer hit the headlines in 2013 and sparked wide media debate.
The good news for those that have throat cancer associated with HPV, is that these tumours generally respond very well to current treatments and have a three year survival rate of around 93%.
Not all throat cancers can be treated equally
Unlike HPV-positive disease, HPV-negative throat cancers have a relatively poor long-term survival rate. The reason for this difference seems to be because HPV-positive cancers have a built-in sensitivity to radiotherapy – the main method employed to treat these patients.
Cells infected with the HPV virus lose control of the mechanisms that correct errors in DNA. This means when radiation is applied to damage the tumour DNA, the HPV-positive cells will not be able to repair the damage and die.
The success of treating HPV-positive cancers with chemoradiotherapy means that researchers can now look for ways to give patients the lowest dose of treatment possible. This is particularly important because most patients with HPV positive cancer are cured at a relatively young age, and the side effects of treatment can have a big impact on their future health and wellbeing.
HPV-negative throat cancers don’t have the inbuilt weakness of those infected by the virus, so are much harder to treat.
Treatments for HPV-negative cancers
In a recent review published in the Journal of Clinical Oncology, the ICR’s Professor Kevin Harrington summarises the current treatment options for HPV-negative disease.
“Currently the best option for patients is chemoradiotherapy. This involves first of all treating the patient with a drug that makes the tumour more sensitive to radiation, and then applying radiotherapy to the affected area. Depending on where the tumour is, surgery is an additional option,” explains Professor Harrington.
“While there’s a higher incidence of throat cancers due to HPV, those virus-linked cancers have much higher survival rates. Patients with HPV-negative disease continue to have unacceptably poor outcomes.”
Many clinical trials have been carried out to test different combinations of chemotherapy drugs and radiotherapy, but very few have shown any improvement to the current method and upping the dose of therapy almost always resulted in worsening the side effects experienced by patients.
Hope for the future
Cancer researchers around the world, including those based at the ICR, are trying to improve upon existing treatments and devise new ways to tackle HPV-negative throat cancer.
Making the cancer more sensitive to radiotherapy is one possible approach, and very early studies suggest combining radiotherapy with drugs like cetuximab, an anti-growth factor receptor antibody, may be effective. However there have been variable results in early small scale trials, and data from larger scale trials is urgently needed.
Another approach is to mimic the HPV virus, by making it harder for cancer cells to repair their DNA. PARP inhibitors are drugs that make it harder for cancer cells to repair DNA breaks, such as those caused by radiotherapy.
Olaparib is one such PARP inhibitor, and was developed as a cancer treatment as a result of 20 years of ground-breaking research here at the ICR. Olaparib was the first cancer drug to be approved that is directed against an inherited genetic mutation, and phase I clinical trials have shown that the drug is well tolerated in throat cancer patients. A larger scale trial is currently recruiting patients with HPV-negative throat cancer and will test if combining Olaparib with radiotherapy could be another treatment option.
Other targeted therapies in clinical trials include cell-cycle checkpoint inhibitors that target genes such as ATR, CHK1 or WEE1.
Professor Harrington told me of his hopes for the future: “Identifying new biomarkers, uncovering the genetic causes of the disease and a greater understanding of the immune system’s role in cancer will be crucial for developing new effective treatments.”
“Much more work has to be done to find new treatments and combinations of treatments that give HPV-negative throat cancer patients the best chance of survival and the best possible quality of life.”
So while the future is hopeful, more ground-breaking research and clinical trials will be needed before we will see similar outcomes between throat cancer patients with and without HPV.
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