MRI for Differentiation between HPV-Positive and HPV-Negative Oropharyngeal Squamous Cell Carcinoma: A Systematic Review

Abstract

Human papillomavirus (HPV) is an important risk factor for oropharyngeal squamous cell carcinoma (OPSCC). HPV-positive (HPV+) cases are associated with a different pathophysiology, microstructure, and prognosis compared to HPV-negative (HPV-) cases. This review aimed to investigate the potential of magnetic resonance imaging (MRI) to discriminate between HPV+ and HPV- tumours and predict HPV status in OPSCC patients. A systematic literature search was performed on 15 December 2022 on EMBASE, MEDLINE ALL, Web of Science, and Cochrane according to PRISMA guidelines. Twenty-eight studies (n = 2634 patients) were included. Five, nineteen, and seven studies investigated structural MRI (e.g., T1, T2-weighted), diffusion-weighted MRI, and other sequences, respectively. Three out of four studies found that HPV+ tumours were significantly smaller in size, and their lymph node metastases were more cystic in structure than HPV- ones. Eleven out of thirteen studies found that the mean apparent diffusion coefficient was significantly higher in HPV- than HPV+ primary tumours. Other sequences need further investigation. Fourteen studies used MRI to predict HPV status using clinical, radiological, and radiomics features. The reported areas under the curve (AUC) values ranged between 0.697 and 0.944. MRI can potentially be used to find differences between HPV+ and HPV- OPSCC patients and predict HPV status with reasonable accuracy. Larger studies with external model validation using independent datasets are needed before clinical implementation.

Keywords: apparent diffusion coefficient; head and neck carcinoma; human papillomavirus; magnetic resonance imaging; oropharyngeal squamous cell carcinoma; systematic review.

Figure 1

Flowchart of study selection, consistent with preferred reporting items for systematic reviews (PRISMA) statement [33].

Figure 2

Overview of QUADAS-2 results. RoB = risk of bias; Appl = applicability.

Figure 3

Mean apparent diffusion coefficient (ADC_mean) of HPV+ and HPV− lesions with decreasing ADC for HPV− from left to right. If median was reported instead of mean, we used the median. Asterisks (*) denote a significant difference between HPV+ and HPV− groups [2,25,27,28,29,38,39,41,42,44,45,46,49]. A significant difference between HPV+ and HPV− lesions was found in all studies (left of the dashed line), except for Schouten et al. and Han et al. [28,49].