Rational genomic optimization of DNA detection for human papillomavirus type 16 in head and neck squamous cell carcinoma

Saito, Yuki; Favorov, Alexander V.; Forman, Michael; Sakai, Akihiro; Fukusumi, Takahito; Liu, Chao; Sadat, Sayed; Ando, Mizuo; Xu, Guiyin; Khan, Zubair; Pang, John; Valsamakis, Alex; Fisch, Kathleen M.; Califano, Joseph A.

doi:10.1002/hed.26041

Cited by 4 publications

(6 citation statements)

References 19 publications

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Section: Methodsmentioning

confidence: 99%

“…A polymerase chain reaction (PCR)–based test for HPV16 DNA in plasma and salivary rinses was performed on linked, deidentified samples in a Clinical Laboratory Improvement Amendments–certified laboratory at the Johns Hopkins Clinical Medical Microbiology Laboratory (Baltimore, Maryland), as previously reported . Assays were performed on 1 mL of plasma and a 0.5-mL aliquot of saliva rinse, which represented half of the centrifuged cell pellet from an 8-mL saline oral rinse, using primer probe combinations that targeted the E5L2 and E1 regions, as well as the E7 region . Briefly, nucleic acid from plasma and oral rinse samples were extracted using the easyMag instrument (bioMerieux), input and elution volumes were 500 and 50 μL, and quantitative real-time PCR amplification was performed on a 7500 real-time PCR system for 3 genomic regions of HPV16.…”

Section: Methodsmentioning

confidence: 99%

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Lead Time to Recurrence After Posttreatment Plasma and Saliva HPV DNA Testing in Patients With Low-Risk HPV Oropharynx Cancer

Califano

Yousef

Mostafa

et al. 2023

JAMA Otolaryngol Head Neck Surg

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ImportanceHead and neck squamous cell carcinoma is a highly lethal cancer that is often associated with human papillomavirus (HPV). Recent studies have shown promise in the use of HPV DNA detection in salivary rinses and plasma as a factor associated with a future diagnosis of HPV-positive oropharynx cancer (HPVOPC). However, the use of plasma and salivary HPV DNA detection in defining risk for recurrence in the context of a prospective, phase 3, clinical trial coupled with standardized clinical surveillance has not been reported.ObjectiveTo identify patients with low-risk HPVOPC at risk for recurrence by detection of HPV16 DNA in plasma and salivary rinses.Design, Setting, and ParticipantsIn this cohort study, 233 low-risk patients were recruited from 32 head and neck treatment centers in Ireland (1 [3.1%]), the Netherlands (1 [3.1%]), and the UK (30 [93.8%]) as part of the DE-ESCALATE HPV trial, an open-label, phase 3 randomized clinical trial examining treatment with cetuximab vs cisplatin for HPVOPC. Patients were assayed for the presence of HPV16 DNA in plasma and salivary rinse via a quantitative polymerase chain reaction–based assay.Main Outcomes and MeasuresAssay results were associated with risk of recurrence and lead time from HPV16 DNA detection to recurrence.ResultsOf 233 patients, 45 (19.3%) were women, and the mean (SD) age was 57.01 (8.45) years. A total 1040 salivary or blood samples were collected during the course of the study. With a median follow-up of 760 days, the sensitivity and specificity of combined plasma and salivary rinse HPV DNA assays for detecting recurrence were 65% and 87%, respectively. There was a median lead time of positive test to event/recurrence date of 19 days (range, 0-536 days) and mean (SD) of 122 (169.8) days.Conclusion and RelevanceThe results of this cohort study suggest that in the setting of a randomized, prospective, phase 3 trial for low-risk patients with HPVOPC, posttreatment presence of HPV DNA in plasma and salivary rinses is associated with recurrence; a lead time between test positivity and clinical recurrence offers a potential opportunity for earlier detection of recurrence.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Lead Time to Recurrence After Posttreatment Plasma and Saliva HPV DNA Testing in Patients With Low-Risk HPV Oropharynx Cancer

Califano

Yousef

Mostafa

et al. 2023

JAMA Otolaryngol Head Neck Surg

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“…Presence of high-risk HPV was determined using quantitative real-time PCR (qPCR) with highly selective primer-probe combinations (BR E1-5, HR E5L2-4, and E7) as previously described by our group. 14 Each reaction used 20 ng purified genomic DNA from saliva as template and was performed in triplicate. Reverse-transcribed full-length HPV genome was used as a standard.…”

Section: Methodsmentioning

confidence: 99%

Targeting Viral DNA and Promoter Hypermethylation in Salivary Rinses for Recurrent HPV‐Positive Oropharyngeal Cancer

Shen

Saito

Liu

et al. 2020

Otolaryngol.--head neck surg.

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Objective The incidence and survivorship of human papillomavirus (HPV)–associated oropharyngeal squamous cell carcinoma (OPSCC) are increasing. Presence of HPV DNA and epigenetic alterations in salivary rinses are independently associated with clinical prognosis. We evaluated the utility of a combined panel in detecting disease recurrence during surveillance. We also assessed the assay’s applicability in screening for HPV+ OPSCC. Study Design Retrospective cohort study. Setting Two tertiary academic hospitals. Subjects and Methods Forty-nine patients with posttreatment OPSCC were enrolled. Separately, 21 treatment-naive patients and 40 controls were included in the screening analysis. Salivary rinses were obtained from these cohorts and biomarker levels were quantified. Receiver operative characteristic (ROC) curves and multivariate logistic models were used to assess performance of biomarker combinations. Results Eight patients (16.3%) in the posttreatment cohort developed locoregional recurrence. Recurrence was associated with alcohol use (odds ratio [OR], 6.12; 95% confidence interval [CI], 0.26-3.79) and advanced nodal disease (OR, 2.21; 95% CI, 1.52-3.01). A panel of HPV DNA and methylated EDNRB improved detection of recurrent disease (area under the curve [AUC], 0.88) compared to single markers (AUC, 0.69-0.78). Positive biomarkers preceded clinical detection by 2.4 ± 1.6 months and was associated with nearly 40-fold risk of recurrence (OR, 36.4; 95% CI, 1.15-45.22). Within the screening analysis, single biomarkers demonstrated moderate sensitivity and specificity (AUC, 0.59-0.83) in the detection of primary disease. A panel combining HPV DNA markers with methylated EDNRB and methylated PAX5 improved AUC to 0.93. Conclusion Detection of high-risk HPV DNA or aberrant hypermethylation in oral rinses is associated with presence and recurrence of OPSCC. Targeting both markers in saliva may have utility in long-term surveillance.

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“…A 2020 paper by Saito et al demonstrated that detection of HPV16 DNA in salivary rinses can be improved using rational genomic design 55 . They hypothesized that previous detection studies had mediocre findings due to use of older, nonoptimized primer/probe sets that failed to utilize newer technological advances, including whole genome sequencing (WGS) and updated assay design.…”

Section: Salivary Biomarkers Of Hpv‐induced Opsccmentioning

confidence: 99%

“…A 2020 paper by Saito et al demonstrated that detection of HPV16 DNA in salivary rinses can be improved using rational genomic design. 55 They hypothesized that previous detection studies had mediocre findings due to use of older, nonoptimized primer/probe sets that failed to utilize newer technological advances, including whole genome sequencing (WGS) and updated assay design. They analyzed two datasets using WGS of HPV-positive head and neck squamous cell carcinoma and then designed rational primer/ probes that would result in optimal detection of HPV16.…”

Section: Dnamentioning

confidence: 99%

Current salivary biomarkers for detection of human papilloma virus‐induced oropharyngeal squamous cell carcinoma

et al. 2021

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Human papilloma virus (HPV) infection is a key risk factor and etiology for oropharyngeal squamous cell carcinoma (OPSCC). HPV‐induced OPSCC is rapidly increasing in incidence, with men experiencing increased mortality. When identified at an early stage, HPV‐induced OPSCC can be successfully treated. Diagnosis of HPV‐related OPSCC relies on an expert physical examination and invasive biopsy. Since saliva bathes the oropharyngeal mucosa and can be collected noninvasively, saliva obtained via salivary risings is an attractive body fluid for early detection of HPV‐induced OPSCC. A plethora of DNA, RNA, and protein salivary biomarkers have been explored. This review discusses these markers and their robustness for detecting oncogenic HPV in OPSCC saliva samples. Methods detecting HPV DNA were more reliable than those detecting RNA, albeit both require time‐consuming analyses. Salivary HPV proteomics are a new, promising focus of HPV detection research, and while more practical, lag behind nucleic acid detection methods in their development.

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Rational genomic optimization of DNA detection for human papillomavirus type 16 in head and neck squamous cell carcinoma

Cited by 4 publications

References 19 publications

Lead Time to Recurrence After Posttreatment Plasma and Saliva HPV DNA Testing in Patients With Low-Risk HPV Oropharynx Cancer

Lead Time to Recurrence After Posttreatment Plasma and Saliva HPV DNA Testing in Patients With Low-Risk HPV Oropharynx Cancer

Targeting Viral DNA and Promoter Hypermethylation in Salivary Rinses for Recurrent HPV‐Positive Oropharyngeal Cancer

Current salivary biomarkers for detection of human papilloma virus‐induced oropharyngeal squamous cell carcinoma

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