SURVEILLE-HPV - A new post therapeutic surveillance strategy for HPV-driven oropharyngeal cancer based on HPV Circulating DNA measures.
HPV-positive oropharyngeal cancer patients have a much better prognosis that their HPV-negative counterparts. Despite this, Post Treatment Surveillance (PTS) strategy does not take into account HPV status.
HPV Circulating DNA (HPV Ct DNA) has emerged as a promising tool to assess the risk of cancer recurrence following treatment. We assume that this biomarker could be helpful to guide PTS.
The number of systematic PTS visits could be significantly reduced in patients with undetectable HPV Ct DNA whereas a closer clinical and radiological follow up could be performed in case of detectable HPV Ct DNA.
If confirmed, this new strategy could have several benefits including:
* reduction of PTS visits for most HPV-positive patients which implies a potential cost decrease and * Identification of relapse at early stages (before the occurrence of symptoms)
Patient aged 18 years or over
Patient with p16 positive Oropharyngeal squamous cell carcinoma (OPSCC)
Clinical stage T1-4, N0-3, M0 (stages I-III)
Any tobacco status
Uncontrolled intercurrent illness that would limit compliance with study requirements.
Active invasive malignancy within 3 years of inclusion except for non-invasive malignancies such as non-melanomatous carcinoma of the skin or ductal carcinoma in situ of the breast that has/have been surgically cured.
Any other HPV induced cancer within 5 years
Any condition that may jeopardize the patient participation as well as non-contraception for male and female with child-bearing potential, pregnancy or breast-feeding
Parallel
HPV16 Ct-DNA dosing
Biological/VaccineDroplet based digital PCR (ddPCR) technology is a novel method for performing digital PCR. A sample is fractionated into 20,000 droplets, PCR amplification of the template molecules occurs in each individual droplet. ddPCR allows to generate quantitative and accurate data without standard curves and also present higher sensitivity compared to conventional quantitative PCR (qPCR). Indeed, this method is based on the realization of millions of single-molecule PCRs in parallel in independent compartment (here droplets of an emulsion) and consequently avoids the bias seen in conventional PCR. ddPCR offers an optimized approach for the sensitive detection and quantification of low-target-abundance biological samples. DNA extraction will be planned on 1 mL of plasma, which will further increase the sensitivity of our technique initially based on only 200µL of DNA extracted plasma.
Negative Predictive Value (NPV) of HPV16 ct-DNA
The presence of HPV16 ct-DNA will be evaluated by ddPCR. NPV will be defined as 2 successive HPV16 ct-DNA negative results.
5- year Negative Predictive Value
The presence of HPV16 ct-DNA will be evaluated by ddPCR. NPV will be defined as 2 successive HPV16 ct-DNA negative results.
Positive Predictive Value (PPV) of HPV16 ct-DNA
The presence of HPV16 ct-DNA will be evaluated by ddPCR. PPV will be defined as 2 successive HPV16 ct-DNA positive results.
Rate of relapses detected by HPV16 ct-DNA
The proportion of patients with relapse detected by HPV16 ct-DNA without any other symptoms.
Disease-free survival
Disease-free survival (DFS) is defined as the delay between date of inclusion and tumor relapse (local, regional, or distant) or death from any cause, whichever occurs first.
