An appraisal of pivotal evaluation designs in validating noninvasive biomarkers for head and neck cancer detection

Figures & data

Table 1. Characteristics of head and neck diagnostic biomarker studies utilizing the PRoBE design.

Authors	Publication year	Study location	Head and neck cancer subtype	Noninvasive specimen	Biomarker type	Biomarker(s)	Form of application	Reference standard	Main study conclusion(s)	Reference
Dyckhoff et al.	2011	Germany	Parotid carcinomas	Gland-specific saliva	Proteomic	CA-19-9	Single	Histopathology	Preoperative marker assay may be helpful in discriminating malignant and benign parotid lesions.	[10]
Martin et al.	2015	USA	Oral carcinoma	Whole saliva	Transcriptomic	DUSP1, SAT, OAZ1	Combined	Histopathology	Salivary mRNA markers can differentiate suspicious lesions into high-risk and low-risk classes.	[9]
Szanto et al.	2012	Hungary	Oral carcinoma	Whole saliva	Proteomic	Annexin-1, Peroxiredoxin-2	Combined	Histopathology	Targeted proteomic analysis of saliva may become the method of choice applicable for early OSCC detection.	[11]

Table 2. Risk of Bias domain of the QUADAS-2 tool for methodological assessment of PRoBE studies.

Study authors (year)	Risk of bias
	Patient selection	Index test	Reference standard	Flow and timing
Dyckhoff et al. (2011)	?	☺	☺	☺
Martin et al. (2015)	?	☺	☺	☺
Szanto et al. (2012)	☹	☹	?	?

☺ low risk; ☹ high risk; ? unclear risk.

Dyckhoff G, Warta R, Gonnermann A, et al. Carbohydrate antigen 19-9 in saliva: possible preoperative marker of malignancy in parotid tumors. Otolaryngol Head Neck Surg. 2011;145(5):772–777.

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Martin JL, Gottehrer N, Zalesin H, et al. Evaluation of salivary transcriptome markers for the early detection of oral squamous cell cancer in a prospective blinded trial. Compend Contin Educ Dent. 2015;36(5):365–373.

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Szanto I, Mark L, Bona A, et al. High-throughput screening of saliva for early detection of oral cancer: a pilot study. Technol Cancer Res Treat. 2012;11(2):181–188.

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