ctDNA testing and HPV: Highlights from Interview with Daniel L. Faden, MD
Dr. Faden is a head and neck surgical oncologist and scientist in the department of Otolaryngology–Head and Neck Surgery at the Harvard Medical School.
What is ctDNA testing?
All cells release fragments of DNA into the circulation; these are called Cell free DNA. When it comes from a tumor cell, we call that circulating tumor DNA. Cancers that are caused by viruses like HPV also release fragments of the viral DNA into the blood. In the case of HPV-associate cancers, we call that circulating tumor HPV DNA. My lab has developed approaches to detect circulating tumor HPV DNA in the blood and we’ve used these to do a number of different studies looking at various clinical questions.
Benefits of ctDNA testing
In our first major study we showed that this blood-based approach to diagnosing HPV-associated head and neck cancer actually outperforms tissue biopsy in its diagnostic accuracy when patients are first presenting with their cancer.
In another study, we explored how to monitor patients’ treatment. Our studies have shown that ctHPVDNA blood testing can be more reliable than the typical ways we monitor for a recurrence, or how we predict if a patient has responded to treatment, or not.
The future of ctDNA testing
It is likely that in the future we will be diagnosing and monitoring most cancers with these types of blood based tests. In terms of HPV associated cancers, ctDNA testing can be used to improve care for patients. For example, in head and neck cancer, unlike cervical cancer, there are no screening tests. We have shown, using blood samples collected before patients ever develop their cancers, that we can detect these cancers years ahead of time. So, in the future, it’s easy to imagine using these types of approaches as screening tests, in certain settings. We definitely aren’t there yet, but I believe, one day, traditional screening approaches will probably be replaced by blood based tests that screen for many cancers at once.
HPV Research: Broadly, what is and isn’t known?
There is a lot we still don’t understand about HPV-associated cancers. For example, it takes about 20-30 years between an HPV infection and then throat cancer developing. We don’t really know what happens in that interim period. It’s kind of a black box. Why the HPV infected cells suddenly become cancer is not very well understood. We know that around 1% of the population will have HPV 16 in their mouth at any given time. If you follow those people across time, most will clear it within a year. But it’s not clear why certain people clear the virus while others don’t and develop a cancer. This appears to be, at least partially, related to a genetic factor in the immune system. The data suggests that people who have certain features in their immune system are more disposed to developing an HPV associated cancer. We do know that immunocompromised patients like HIV positive patients are also more likely to get an HPV associated cancer and this supports the hypothesis that the immune system is central.
The Different Types of HPV
There are many types of HPV. Only certain types are known to cause cancer. The most common type is HPV 16. You can also go much deeper than just the genotypes. Our group has done work showing, for example, that specific subtypes of HPV16, called sublineages, can behave more aggressively than others. In addition, these different types of HPV come from different parts of the world, and evolved in different parts of the world. So, we have European or African variants and they evolved to be more efficient in different ethnic groups. There are beautiful studies showing that the virus is more effective or less effective, more or less aggressive, in different groups of people. Certain viruses have adapted to be more carcinogenic in certain ethnicities than others, over a long period of time. In general, we are still trying to learn how different variants of the virus behave differently and so we can’t use this information in treatment or diagnosis, yet, but perhaps in the future,
HPV Associated Cancers and the Future
There is a lot of room for improvement in terms of the HPV blood tests that are currently available from my lab, and others.
We know that HPV associated cancer of the throat are more responsive to treatment than non HPV-associated cancer. Therefore, there is a movement to reduce treatment for these patients. However, how to appropriately choose which patients should get less or more treatment is still unclear. We are studying how to use these ctHPVDNA blood tests to determine how to personalize a patient’s treatment- choosing just enough treatment to kill the cancer but no more, to lessen the side effects.