Purpose: This is first Australian population-based retrospective study in HPV-induced OPSCCs utilising CT. Contrast enhanced computed tomography (CECT) was utilised to assess if imaging findings of metastatic cystic lymph nodes (LNs) can predict human papillomavirus (HPV) status, as defined by p16 immunostaining of oropharyngeal squamous cell carcinomas (OPSCCs). Materials and Methods: The location and p16 status of primary tumours and LNs were recorded. Metastatic LNs were assessed for size, shape, margins and cystic changes. Hounsfield Units (HU) value of primary tumours and LNs were measured and tabulated. p16-positive and p16-negative groups were compared with respect to these variables. The two-sample t test and two-sample Mann–Whitney test was used. Results: A total of 364 CECT scans were reviewed with 209 patients (187 p16 positive and 22 p16 negative). Primary sites of OPSCCs were tonsils (58.8%), base of tongue (37.4%) and other oropharyngeal sites (3.8%). The HU values of p16-positive OPSCCs with mean of 78.6HU; 95% CI (76.5–80.8) were lower for p16-negative tumours, mean 96.0 HU CI 95% (85.5–106.6) for all oropharyngeal sub-sites. The mean HU values of p16-positive and p16-negative metastatic LNs were 38.8 HU 95% CI: (13–103 HU) versus 88.7 HU 95% CI: (54–131) (P < 0.0001). Conclusions: The association between p16-positive status and the tonsillar cancer site is very high. Imaging features of p16-positive metastatic LNs include relatively large cystic neck nodes with low HU values. This is an imaging signature of p16-positive OPSCCs and can potentially influence patient’s early diagnosis and prognosis.