Blood and saliva‐derived ctDNA is a marker of residual disease after treatment and correlates with recurrence in human papillomavirus‐associated head and neck cancer

Abstract

BackgroundThere is an alarming increase in human papillomavirus‐associated head and neck cancer (HNC), reaching epidemic levels. While patient prognosis is generally good, off‐target treatment effects are associated with decreased quality of life. Thus, non‐invasive strategies to predict treatment response and risk of recurrence could help de‐escalate treatment. In this study, we tested circulating tumor (ct)DNA in liquid biopsies (blood/saliva) of HPV‐positive HNC patients to assess treatment response and disease progression.MethodsA total of 235 blood and saliva samples were collected from 60 HPV‐positive and 17 HPV‐negative HNC patients (control group) before and/or after treatment. Samples were analyzed using ddPCR for HPV16/18/31/33/35/45 and correlated with imaging and pathological examination.ResultsHPV‐ctDNA detection was significantly higher prior to treatment (91%) than after treatment (8.0%) (χ2 p < 0.00001), with high concordance between saliva and blood (93%). In matched samples, all patients positive for ctDNA before treatment showed significant reductions in ctDNA levels post treatment (p < 0.0001). All but one patient with persistent ctDNA after treatment showed residual tumor and subsequent recurrence. Finally, fragmentomic analysis revealed shifts in cell‐free DNA fragment size after treatment, suggesting a complementary biomarker for treatment response.ConclusionsBlood and saliva were found to be good sources of HPV‐ctDNA. The presence of ctDNA strongly correlated with treatment response, demonstrating clinical utility as a non‐invasive biomarker to monitor tumor progression in HPV‐positive HNC. Liquid biopsy based ctDNA testing could be an effective approach to predict recurrence and stratify patients for de‐escalation of treatment, thereby improving quality of life.

Accuracy of Salivary Circulating Tumor Human Papillomavirus DNA in Detecting Oropharyngeal Cancer

“…Looking first at the individual sensitivities, specificities, PLRs, NLRs, and DORs of salivary ctHPV DNA in detecting all OP cancers, a notable trend arises. Values derived from Ferrier et al were the strongest, whereas those from Wang et al were the lowest values relative to all studies. This suggests upgrades in testing technology following their publication may have enhanced detective accuracy—a theory supported by Brooks et al having the second highest DOR and second most recent publication date.…”

“…Brooks et al demonstrated the highest sensitivity with a value of 88% (95% CI, 40%-99%). Ahn et al and Ferrier et al shared the highest specificity results, but the former study had a slightly narrower CI at 97% (95% CI, 90%-99%) compared with the latter’s 97% (95% CI, 88%-99%). The pooled sensitivity and specificity across all studies were 64% (95% CI, 36%-85%) and 89% (95% CI, 46%-99%), respectively.…”

“…Note that the forest plot was created on a log scale for clearer visualization, but as a result, values must be retransformed via an exponential (with base e ) for interpretation (eTable 2 in Supplement 1). Ferrier et al demonstrated the highest PLR and highest DOR with values of 30.08 (95% CI, 6.18-146.40) and 220.70 (95% CI, 32.92-1479.84), respectively. Brooks et al and Ferrier et al shared the lowest NLR, but the latter study had a narrowest CI at 0.14 (95% CI, 0.06-0.32) compared with the former’s 0.14 (95% CI, 0.01-1.96).…”

“…As shown in Figure 1, 440 articles were initially identified and later narrowed to 6 studies that met the aforementioned inclusion criteria . All 6 articles demonstrated low risk of bias and low applicability concerns across all domains assessed via the QUADAS-2 tool (eTable 1 in Supplement 1).…”

PBRM1 presents a potential ctDNA marker to monitor response to neoadjuvant chemotherapy in cervical cancer

“… 14 In cervical cancer, HPV (human papilloma virus) ctDNA was found to be a marker for early detection of relapse and residual disease. 15 , 16 , 17 Nevertheless, the genetic variants in ctDNA associated with the response to NACT in LACC patients are still unexplored.…”