In HPV-driven OPSCC surveillance
Serial NavDx Testing Assists in Earlier Detection of Residual/Recurrent Disease
Although imaging and physical exams have long been the standard of care, their ability to detect recurrence early is limited4,5,10
- PET/CT performance metrics: ~88%4,5,10 sensitivity/specificity; 94% NPV (negative predictive value) and 76% PPV (positive predictive value)4,5,10
- Anatomical changes post-surgery and post-chemoradiation complicate the predictive value of physical exam, endoscopy, and costly imaging studies4
- Imaging can only confirm locoregional tumors that have grown to a detectable size, and can miss distant metastases outside the region being scanned5
Occult recurrences of HPV+ oropharyngeal cancer can easily be missed by imaging if scanning is limited to a defined section of the body
13-25% of patients will relapse with locoregional or distant metastases.11-13 Fear of recurrence is your patient’s #1 concern,
In a large retrospective study (N=1,076), occult recurrences were accurately detected in patients with a single positive TTMV-HPV DNA Score3
- NavDx testing was the first indication of recurrence, predating clinical symptoms or imaging among patients with no evidence of disease3
- 53% (29/55) of confirmed recurrences occurred in patients >12 months post-completion of therapy2,3
Why wait for physical symptoms to appear? A positive TTMV-HPV DNA Score was the first indication of recurrence in 97% (57/59) of asymptomatic patients3 *†
*Of 1,076 patients tested during surveillance, 80 (7.4%) had at least one positive TTMV-HPV DNA Score. Of these, 59 (74%) had either indeterminant (IND) disease status or no evidence of disease (NED) at time of their positive test Score, while 21 (26%) were noted as having clinically active disease at time of their first positive Score. Nearly half, 38 (48%) were tested >12 months after completion of definitive therapy, while 27 (34%) and 15 (19%) were tested at 6-12 months, and 3-6 months, respectively.
†57 of the 59 (96.66%) patients with IND or NED status, who tested positive for TTMV-HPV DNA, were later proven to have recurrent disease (on imaging and/or biopsy), suggesting the presence of clinically occult recurrence at time of their positive test result. Longer follow-up was needed to identify recurrent cancer in 2 of the remaining 4 IND and NED patients under surveillance. All 21 patients with active disease reported at the time of TTMV-HPV DNA testing were confirmed to have recurrent disease.
A multi-institutional retrospective observational cohort study (N=573) concluded:
- Serial testing of TTMV-HPV DNA during surveillance is highly accurate and reliable at detecting molecular residual disease (MRD) and recurrence1,2
- NavDx testing resulted in few false negatives and few missed recurrences, especially among patients with a known positive result preceding a negative result2
- Recurrence-free and overall survival were significantly worse for patients with any positive TTMV-HPV DNA test result identified during surveillance (p<0.0001)2
Survival based on surveillance TTMV-HPV DNA test results‡
‡Survival among HPV-associated oropharyngeal cancer survivors based on surveillance TTMV-HPV DNA test results. Recurrence-free survival (A) and overall survival (B) curves separated by patients in the entire study cohort with negative surveillance TTMV-HPV DNA results vs. those with a positive TTMV-HPV DNA test result at any timepoint during surveillance; Kaplan–Meier method; log-rank testing (two-sided),
Survival after recurrence is significantly better identifying recurrences early Detect recurrences a median of 4 months earlier with the NavDx.4
Testing Schedule
Clinical practice guidelines and CMS coverage policy for recurrence detection include surveillance at specified intervals:
During Surveillance
≤2 years post treatment: every 3 months
3-5 years post treatment: every 6 months
6+ years post treatment: 1 time per year
References
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