Detectable ctDNA Could Suggest Cervical Cancer Treatment

This transcript has been edited for clarity. 

Hello. I’m Dr Maurie Markman, from City of Hope. I’m going to be briefly discussing a very interesting paper that recently appeared in the Journal of Clinical Oncology, “Clinical Validation of Human Papilloma Virus (HPV) Circulating Tumor DNA for Early Detection of Residual Disease After Chemoradiation in Cervical Cancer.” 

The concept of minimal residual disease is becoming very important in oncology. Liquid tumor biopsies in the solid tumor space are increasingly discussed. This type of approach has been used in hematologic malignancy, and certainly in chronic myelogenous leukemia, for a long time. Moving this into the solid tumor space is happening very rapidly. 

In this particular paper which I noted, there had been a pilot study where there was evidence that HPV-related circulating tumor DNA (ctDNA) was shown to be present in a significant number of women who had undergone chemoradiation. 

The paper that we’re talking about here is a prospective, multicenter validation study. A total of 70 patients who had known HPV-related cervical cancer, which is essentially all cervical cancer, were treated. There was a total of 24 recurrent events in this analysis. The primary endpoint was progression-free survival. 

The authors report that the women with undetectable HPV ctDNA at 4-6 weeks post-chemotherapy had a 2-year progression-free survival of 82% vs the women who had detectable HPV ctDNA in the blood, who had a 2-year disease-free survival of only 15%. This was highly statistically significant. 

In fact, the next question that might be asked is, how long before there was clinical evidence of progression of when you had this detectable DNA in the blood? The answer was that the lead time to occurrence was approximately 6 months. 

The argument would be that if you have this HPV-related ctDNA and you can document that at 4-6 weeks, 2 months, or maybe 3 months, this is when you might consider starting — and I think we need more data here to confirm this, but the data here are very impressive — a next line of therapy. 

Obviously, the next question is, what might be available? Here, we’re talking about chemoradiation, so this is therapy of initial disease. In fact, if there’s evidence of recurrence, the approach might be immunotherapy, for which we now have good evidence that a large number of patients find benefit. This would be the option to potentially start the immunotherapy earlier and perhaps improve the efficacy. Again, there is more that needs to be learned here. 

I think this is a provocative study that gives us a lead on how we might, earlier in this patient population, define recurrence, potentially institute therapy for metastatic disease, and potentially have more effective therapy. 

For those of you who are interested in the question of molecular monitoring, and certainly the management of advanced cervical cancer, this is a very important paper and I encourage you to review it.