FOR HEALTHCARE PROVIDERS TREATING HPV+ CANCER

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Act Sooner.

NavDx Testing in

HPV+ Oropharyngeal Cancer Surveillance

Standard OPSCC Surveillance Has Limitations.

Physical exams, nasopharyngeal endoscopy, and imaging have long been the standard of care for post-treatment OPSCC surveillance, but their ability to detect recurrence early is limited by several factors:

    • With a PPV of ~76%55 and specificity of ~88%55, PET/CT positive imaging findings may not represent true recurrence. This could drive unnecessary biopsies, repeat imaging, and patient anxiety.
    • Anatomical changes from surgery and chemoradiotherapy complicate the predictive value of physical exam, nasopharyngeal endoscopy, and imaging1
    • Imaging can only detect locoregional tumors that have grown to a detectable size and may miss distant metastases outside the field of view42
    • Nasopharyngeal endoscopy identifies recurrence in only 0.3–9% of surveillance visits11,56

 

The NavDx test operates at the molecular level and can detect TTMV-HPV DNA fragments in the bloodstream before tumors grow large enough for imaging or exams to find them, and without the false-positive burden that makes imaging findings difficult to act on.

The NavDx Test vs. Standard Surveillance:

Published data1,2,3,55 demonstrate that NavDx testing can substantially outperform PET/CT, particularly in positive predictive value:

Metric NavDx PET/CT Clinical Significance
Sensitivity ≥89%1,2 79-87%55 Comparable ability to detect true recurrence
Specificity ≥97%1,2 ~88%55 NavDx produces far fewer false positives
PPV ≥95%1,3 ~76%55 Positive NavDx results are more reliably actionable
NPV ≥98%1,2 ~94%55 Negative NavDx result provides stronger reassurance

Earlier Detection of Recurrence.

Published data demonstrate that NavDx testing can detect molecular evidence of recurrence a median of 4 months earlier than PET/CT or clinical exam.6,8 This lead-time advantage has direct clinical implications:

 

    • 15–25% of HPV+ OPSCC patients experience locoregional or distant recurrence after treatment3
    • In published research, 69% to 72% of recurrences were asymptomatic at first NavDx detection. Patients felt well and had no clinical findings; NavDx testing found disease before anything else did.2,3
    • Experts have reached strong consensus that earlier identification of locoregional or distant recurrence may improve outcomes by expanding salvage therapy options, including surgical salvage.11

The Problem of Clinically Indeterminate Findings in OPSCC.

Published data demonstrate that NavDx testing can detect molecular evidence of recurrence a median of 4 months earlier than PET/CT or clinical exam.6,8 This lead-time advantage has direct clinical implications:

Standard surveillance generates significant diagnostic uncertainty. Published research shows that across 543 patients at 8 U.S. institutions, 38.7% had at least one clinically indeterminate finding (CIF)—33% from exam, 67% from imaging, with 503 total indeterminate episodes. CIFs were most common in the first year post-treatment (2.1× higher odds in year 1, primarily at 3–6 months). NavDx testing in the CIF setting demonstrated 97.5% overall resolution accuracy. When NavDx testing was positive in a CIF context, 100% of cases were confirmed recurrences (19/19). When negative, 96.7% were confirmed NED (60/62). A positive NavDx result in the setting of an indeterminate clinical finding reduced median time to confirmed diagnosis from 97.5 days to 14 days (p<0.05).39

Survival Impact: What a Positive Result Means.

The survival data from Hanna/Roof 2023 provides important clinical context for interpreting a positive NavDx result during surveillance:

Lang Kuhs et al notes, “Survival after recurrence is significantly better for patients with a single focus of disease and those able to undergo surgical salvage treatment, suggesting that identifying recurrences early may prolong the disease-free interval, with potential for cure in a subset of cases.” 44

Key Supporting Studies.

Berger BM, Hanna GJ, et al. | Clin Cancer Res. 2022 | N=1,0763
In this large multi-institutional retrospective study, 1,076 patients were tested during post-treatment surveillance. Of the 80 patients (7.4%) who had at least one positive TTMV Score:

    • 59 patients (74%) had either indeterminate (IND) or no evidence of disease (NED) clinical disease status at the time of their positive test
    • Of those 59 patients, 57 (97%) were subsequently confirmed to have recurrent disease. The NavDx result was the first indication of recurrence, preceding symptoms, clinical exams, and imaging
    • Nearly half (48%) of the 80 patients with a positive test had been tested and recurrence identified more than 12 months after completion of definitive therapy
    • 97% of asymptomatic patients with a positive NavDx result were subsequently confirmed to have recurrent disease—NavDx detected what clinical exams and imaging had not yet found.

Hanna GJ, Roof SA, Jabalee J, et al. | Clin Cancer Res. 2023 | N=5732
A multi-institutional retrospective observational cohort study of 573 patients evaluated serial TTMV-HPV DNA testing during OPSCC surveillance:

  • NavDx testing resulted in few false negatives and few missed recurrences, especially among patients with a known positive result preceding a negative result, with a per-patient NPV of 98.4%
  • Recurrence-free and overall survival were significantly worse for patients with any positive TTMV-HPV DNA test result during surveillance. with an estimated recurrence rate 22.5 times higher and chance of survival 8 times lower (p<0.0001)
  • NavDx was the first sign of recurrence in 69% of patients with confirmed recurrent disease, with a median lead time of 47–53 days before imaging-confirmed disease

Ferrandino RM, Chen S, et al. | JAMA Otolaryngol Head Neck Surg. 2023 | N=290 (591 tests)1
A single-institution study evaluating NavDx for both diagnosis and surveillance of HPV-associated oropharyngeal cancer. In the surveillance subgroup, NavDx achieved per-test 88.4% sensitivity, 100% specificity, 100% PPV, and 99% NPV, demonstrating exceptional accuracy in a clinical-practice population. Overall diagnostic accuracy was 97.5%.

Roof et al., 2024 | Oral Oncology | N=543, 8 U.S. institutions39
NavDx testing resolved clinically indeterminate surveillance findings (CIFs) with 97.5% accuracy. Positive NavDx results in the CIF setting demonstrated 100% concordance with confirmed recurrence; negative NavDx results showed 96.7% NED confirmation. Median time to diagnosis with a positive NavDx test in the CIF context was 14 days vs. 97.5 days without NavDx testing (p<0.05). CIFs occurred during surveillance of 38.7% of patients, concentrated in year 1 of follow-up.

NavDx Testing in

HPV+ Anal Cancer Surveillance

Standard ASCC Surveillance Has Limitations.

Post-treatment surveillance for HPV+ anal squamous cell carcinoma (ASCC) presents distinct clinical challenges that make molecular monitoring particularly valuable:

    • Standard ASCC surveillance relies on digital anorectal exam (DARE), anoscopy or high-resolution anoscopy (HRA), and MRI imaging, each with significant limitations in sensitivity, specificity, or accessibility
    • Post-chemoradiotherapy (CRT) imaging is typically delayed until approximately 26 weeks post-treatment due to treatment-related inflammation, fibrosis, and tissue changes that make earlier imaging unreliable, creating a window where disease status is uncertain
    • Clinically indeterminate findings (CIFs) are common. In the foundational study for NavDx testing in ASCC and its follow-on study, 42-44% of patients experienced at least one CIF during surveillance visits,4,5 resulting in repeat procedures and generating patient anxiety.
    • High-resolution anoscopy (HRA), the most sensitive standard tool, is geographically concentrated at specialized centers, creating significant access disparities for patients in rural areas

 

NavDx testing can provide molecular surveillance during the post-CRT imaging delay and throughout the surveillance period, offering objective disease status information based on a simple blood draw.

The NavDx Test vs. Standard ASCC Surveillance Modalities.

Across two multi-site studies,4,5 standard ASCC surveillance tools generated clinically indeterminate findings (CIFs) in 39–42% of patients. NavDx testing offers a substantially lower indeterminate rate and higher positive predictive value:

Modality PPV NPV Key Limitation
NavDx ≥96.0%4,5 ≥92.5%4,5 1.3% indeterminate rate
Anoscopy (AIN2+ detection) 41.7–64.2%58,59 75.0–93.0%58,59 39.9% indeterminate rate
DARE (digital anorectal exam) 29.6%60 98.8%60 Low sensitivity; low PPV
MRI  44.8%61 95.7%61 Delayed ~26 weeks post-CRT; 17% indeterminate rate
CT  36.7%61 91.1%61 

Earlier Detection of Recurrence.

Published data demonstrate that NavDx testing can detect molecular evidence of recurrence a median of approximately 2 months earlier than imaging or clinical exam.5 This lead-time advantage has direct clinical implications:

    • 20-30% of HPV+ ASCC patients experience locoregional or distant recurrence after treatment
    • Earlier identification of recurrence may allow intervention while disease burden is still limited. Patients with fewer metastatic lesions at treatment initiation have better long-term outcomes than those with more extensive disease.51
    • Earlier identification of recurrence may expand salvage therapy options, including sphincter-preserving limited surgery for the earliest local recurrences, allowing patients to avoid permanent colostomy or additional courses of chemoradiation or brachytherapy.51

The Problem of Clinically Indeterminate Findings in ASCC.

Clinically indeterminate findings (CIFs) are one of the most challenging aspects of ASCC surveillance, but NavDx testing can help resolve them. Data from two multi-site studies4,5 show:

    • 42-44% of patients had ≥1 CIF during surveillance visits.4,5
    • Imaging was indeterminate in 17% of visits and clinical exam in 7% of visits. NavDx was only indeterminate 1.3% of the time, 5-13 times less than standard clinical surveillance methods.5
    • CIF odds were 1.86× higher in year 1 vs. year 2 post-treatment.5 The highest-risk window for recurrence is also when CIFs are most frequent.
    • NavDx testing resolved CIFs with 92%-94% accuracy with a single test.4,5
    • 100% positive concordance was found. Every positive NavDx result performed on a patient with a CIF was found to indicate the presence of a true recurrence.5
    • When NavDx testing is positive in a CIF setting, median lead time to confirmed recurrence is 29 days.5

Survival Impact: What a Positive Result Means.

Patients with positive post-treatment NavDx results had significantly worse recurrence-free survival than those with consistently negative test results.4 Consistent negative TTMV Scores during ASCC surveillance is associated with favorable outcomes and provides meaningful clinical reassurance.
Among patients who had a positive pre-treatment NavDx test and were tested again within 3 months post-treatment, 76.0% (19/25) showed resolution of detectable TTMV-HPV DNA. Resolution of positive NavDx results correlated with significantly better recurrence-free survival (p=0.0099, trending toward significance).4

Access and Equity Considerations.

High-resolution anoscopy (HRA), the most sensitive tool for ASCC surveillance, is geographically concentrated at specialized centers, creating significant access disparities for patients in rural areas or those receiving care at HIV care facilities. NavDx testing, requiring only a standard blood draw, may help address this gap by enabling surveillance-quality molecular monitoring at any location where blood can be drawn. Naveris can help arrange patient blood draws outside of your facility to enable access to the NavDx test, wherever your patients are located.

 

Learn about NavDx-Arranged Phlebotomy →

Key Supporting Studies.

Kabarriti R, Lloyd S, Jabalee J, et al. | Cancers (Basel). 2025 | N=117 (368 tests)4
The foundational multi-site NavDx ASCC clinical validation study. 117 patients at 7 U.S. centers; 368 total tests; median follow-up 2 years. 90.6% treated with CRT. HPV16 was the predominant genotype (91.4%). Key findings:

    • Pre-treatment NavDx detection rate: 85%, establishing TTMV®-HPV DNA as a reliable baseline biomarker in ASCC
    • Post-treatment per-patient performance: sensitivity 82.8%, specificity 98.4%, PPV 96.0%, NPV 92.5%
    • Lead time advantage: median 59 days before imaging or clinical detection of recurrence
    • CIF resolution: NavDx correctly classified recurrence status in 33/35 CIF events (94.3%)
    • CIF frequency: 44% (52/117) of patients had ≥1 CIF during post-treatment surveillance.
    • NavDx indeterminate rate (1.9% (5/267) of tests)

 

Kabarriti R, Lloyd S, Jabalee J, et al. | Cancers (Basel). 2026 | N=233 (603 tests)5
The dedicated CIF resolution study, the largest multi-site NavDx ASCC study to date. 233 patients at 10 U.S. centers; 603 post-treatment NavDx tests; data January 2020–February 2025. Key findings:

    • CIF frequency: 42% (90/215) of patients had ≥1 CIF during post-treatment surveillance; 214 total CIFs (46% from exam findings, 54% from imaging)
    • Indeterminate rates by modality: Imaging 17%; Clinical exam 7%; NavDx 1.3%
    • Overall CIF resolution accuracy: 92% (48/52 evaluable CIF–NavDx pairs)
    • CIF resolution: 96% accuracy within 4 months, and 88% after 4 months post-treatment
    • When NavDx testing is positive in a CIF setting: 100% concordance with confirmed recurrence; first sign of recurrence in 73% of these patients; median lead time 29 days
    • When NavDx testing is negative in a CIF setting: 90% concordance with no recurrence (4/41 false negatives, all locoregional)
    • Pre-treatment detection rate: 86.2% (95% CI 78.8–91.7%; N=123 patients)

 

Huffman BM, et al. | J Immunother Cancer. 2024 | N=2645
A phase II clinical trial analysis evaluating NavDx as a biomarker of pembrolizumab efficacy in advanced ASCC. NavDx TTMV-HPV DNA was detected in 25 of 26 patients with HPV+ ASCC who had pre-treatment testing. Patients who had clinical benefit from pembrolizumab had decreasing TTMV- HPV DNA scores from baseline to 3 and 6 weeks of therapy.

References

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