Plasma HPV cell-free DNA monitoring in advanced HPV-associated oropharyngeal cancer

Hanna, Glenn J.; Supplee, Julianna; Kuang, Yanan; Mahmood, Umair; Lau, Christie J.; Haddad, Robert I.; Jänne, Pasi A.; Paweletz, Cloud P.

doi:10.1093/annonc/mdy251

Cited by 101 publications

(97 citation statements)

References 22 publications

(24 reference statements)

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“…According to collection of data/samples, five studies had a prospective design [ 24 , 27 , 28 , 30 , 37 ], whereas four studies were purely retrospective [ 23 , 25 , 29 , 33 ]. Seven studies did not report how data/samples were collected [ 22 , 26 , 31 , 32 , 34 , 35 , 36 ] ( Table 1 , Table S1 ).…”

Section: Resultsmentioning

confidence: 99%

“…One study [ 27 ] used “HPV16-detect” and compared sensitivity and specificity via real-time PCR. Additionally, eight studies [ 25 , 28 , 29 , 30 , 33 , 35 , 36 , 37 ] used droplet digital PCR (ddPCR). Damerla et al [ 29 ] and Jeannot et al [ 33 ] compared ddPCR with qPCR and they reported more sensitive values by using ddPCR at lower cfHPV-DNA concentrations.…”

Section: Resultsmentioning

confidence: 99%

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Cell-Free HPV-DNA as a Biomarker for Oropharyngeal Squamous Cell Carcinoma—A Step Towards Personalized Medicine?

Wuerdemann

Jain

Adams

et al. 2020

Cancers

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Global incidences of oropharyngeal squamous cell carcinoma (OPSCC) are rising due to an association with high-risk human papillomavirus (HPV). Although there is an improved overall survival of HPV-related OPSCC; up to 25% of the patients develop recurrent or distant metastatic disease with a fatal outcomes. Biomarkers to monitor this disease are not established. This meta-analysis reviews the role of cell-free HPV DNA in liquid biopsy (LB) as a biomarker for HPV-related OPSCC. Pubmed, Livivo, and Cochrane Library databases were searched from inception to August, 2020. All studies were analyzed by Meta-DiSc 1.4 and Stata 16.0 statistical software. In total, 16 studies were considered for systematic review, whereas 11 studies met inclusion criteria for meta-analysis, respectively. Pooled sensitivity of cfHPV-DNA at first diagnosis and during follow-up was 0.81 (95% CI; 0.78–0.84) and 0.73 (95% CI; 0.57–0.86), while pooled specificity was 0.98 (95% CI; 0.96–0.99) and 1 (95% CI; 0.99–1). The diagnostic odds ratio (DOR) at first diagnosis was 200.60 (95% CI; 93.31–431.22) and 300.31 (95% CI; 60.94–1479.88) during follow-up. The area under the curve (AUC) of summary receiver operating characteristic (SROC) was 0.99 at first diagnosis and 1.00 during follow-up, respectively. In conclusion, cfHPV-DNA presents a potential biomarker with high specificity in patients with HPV-related OPSCC.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Cell-Free HPV-DNA as a Biomarker for Oropharyngeal Squamous Cell Carcinoma—A Step Towards Personalized Medicine?

Wuerdemann

Jain

Adams

et al. 2020

Cancers

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“…In the context of metastatic disease, published longitudinal data is limited. Circulating HPV-DNA levels have been reported in three small studies in HPV-driven cancers to have changes consistent with the disease burden and treatment response 22,32,33 . This is in contrast with the results found in our study, which did not find any correlation between circulating HPV-DNA levels correlating with disease response to treatment.…”

Section: Discussionmentioning

confidence: 95%

“…This is in contrast with the results found in our study, which did not find any correlation between circulating HPV-DNA levels correlating with disease response to treatment. The three published studies used ddPCR to detect circulating HPV-DNA, and included patients with metastatic HPV-driven cervical cancer (n = 19); a case report in metastatic HPV-driven anal cancer (n = 1); and metastatic HPV-OPCSCC (n = 22) 22,32,33 . It is worth noting that these studies all used different definitions of tumor burden measurements to our study; one used RECIST 1.0 criteria, one used immune-related total measurable tumor burden, and one used another novel measurement method to derive the total tumour burden.…”

Section: Discussionmentioning

confidence: 99%

A comparative study of extracellular vesicle-associated and cell-free DNA and RNA for HPV detection in oropharyngeal squamous cell carcinoma

Nguyen

Meehan

Pereira

et al. 2020

Sci Rep

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Purpose: This study compares the detection sensitivity of two separate liquid biopsy sources, cell-free (cf) DNA/RNA and extracellular vesicle (EV)-associated DNA/RNA (EV-DNA/RNA), to identify circulating Human Papilloma Virus (HPV) DNA/RNA in plasma obtained from patients with oropharyngeal squamous cell carcinoma (OPCSCC). We also report on the longitudinal changes observed in HPV-DNA levels in response to treatment. Experimental design: A prospective study was conducted that included 22 patients with locally advanced disease and six patients with metastatic OPCSCC. Twenty-three patients had HPV-related OPCSCC defined by p16 immunohistochemistry. Levels of circulating HPV-DNA and HPV-RNA from plasma-derived cf-DNA/RNA and EV-DNA/RNA were quantified using digital droplet PCR. Results: Circulating HPV-DNA was detected with higher sensitivity in cf-DNA compared to EV-DNA at 91% vs. 42% (p = <0.001). Similarly, circulating tumoral HPV-RNA was detected at a higher sensitivity in cf-RNA compared to EV-RNA, at 83% vs. 50% (p = 0.0019). In the locally advanced cohort, 100% (n = 16) of HPV-OPCSCC patients demonstrated a reduction in circulating HPV-DNA levels in cf-DNA following curative treatment, with 81% of patients demonstrating complete clearance to undetectable levels. However, in metastatic HPV-OPCSCC patients (n = 4), HPV-DNA levels did not correlate with treatment response. Conclusion: Our study demonstrates that although HPV-DNA/RNA can be detected in EV associated DNA/RNA, cf-DNA/RNA is the more sensitive liquid biopsy medium. As circulating HPV-DNA levels were found to only correlate with treatment response in the locally advanced but not metastatic setting in our small cohort of patients, the use of HPV-DNA as a dynamic biomarker to monitor treatment response requires further evaluation.

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“…In contrast, when using quantitative reverse transcription PCR to detect HPV16 E6/E7 expression, the presence of circulating HPV16 E6/E7 mRNA at baseline, prior to treatment, was associated with worse progression-free survival and overall survival [56]. This was similarly true of different individual studies, which found that increased levels of pre-treatment HPV16 ctDNA were correlated with worse prognosis [57], and in one study, worse TNM staging as well [58].…”

Section: Circulating Hpv Dna As a Biomarkermentioning

confidence: 97%

Molecular Diagnostics in Human Papillomavirus-Related Head and Neck Squamous Cell Carcinoma

Wai

Strohl

Zante

et al. 2020

Cells

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The incidence of human papillomavirus (HPV)-related head and neck squamous cell carcinoma continues to increase. Accurate diagnosis of the HPV status of a tumor is vital, as HPV+ versus HPV– tumors represent two unique biological and clinical entities with different treatment strategies. High-risk HPV subtypes encode oncoproteins E6 and E7 that disrupt cellular senescence and ultimately drive tumorigenesis. Current methods for detection of HPV take advantage of this established oncogenic pathway and detect HPV at various biological stages. This review article provides an overview of the existing technologies employed for the detection of HPV and their current or potential future role in management and prognostication.

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Plasma HPV cell-free DNA monitoring in advanced HPV-associated oropharyngeal cancer

Abstract: Plasma HPV cfDNA monitoring recapitulates fluctuations in disease status. While blood-based HPV DNA monitoring does not currently have a role in managing HPV+ OPC, these data speak to their broad clinical potential in an era of precision medicine.

Cited by 101 publications

References 22 publications

Cell-Free HPV-DNA as a Biomarker for Oropharyngeal Squamous Cell Carcinoma—A Step Towards Personalized Medicine?

Cell-Free HPV-DNA as a Biomarker for Oropharyngeal Squamous Cell Carcinoma—A Step Towards Personalized Medicine?

A comparative study of extracellular vesicle-associated and cell-free DNA and RNA for HPV detection in oropharyngeal squamous cell carcinoma

Molecular Diagnostics in Human Papillomavirus-Related Head and Neck Squamous Cell Carcinoma

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