Introduction The incidence of human papillomavirus (HPV) related oropharyngeal squamous cell carcinoma (OPSCC) has risen markedly in recent times, including in younger people without the traditional risk factors such as smoking and alcohol consumption. Painless cystic neck metastasis as the initial presentation of HPV OPSCC is well-documented. Suppurative lymphadenitis is an unusual presentation in the high-risk age group. Purpose To describe a case series of patients presenting with suppurative lymphadenitis, later found to have underlying metastatic HPV-related OPSCC from an oropharyngeal primary. Methodology A case series of 7 patients presenting with suppurative lymphadenitis and underlying metastatic HPV OPSCC was analysed. Clinical and demographic data were collated. Results 7 patients (5 male and 2 female) with an average age of 58 presented to the emergency department with painful cervical lymphadenopathy and fever. All patients underwent ultrasound-guided fine needle aspirate (FNA). Malignant cells were only found in 3 specimens. Staphylococcal and Streptococcal species were found on microbiology. Panendoscopy and biopsy was completed in all patients, confirming primary p16+ OPSCC in tonsil or base of tongue. 4 patients were treated with primary chemoradiotherapy, and 3 had surgical resection of the primary with neck dissection, followed by adjuvant therapy. Conclusion Suppurative lymphadenitis can be the initial presentation of metastatic head & neck cancer. FNA may not be accurate in the setting of tissue necrosis and abscess formation. It is imperative to continue investigation until a clear and specific diagnosis is reached. References 1.Pynnonen MA, Gillespie MB, Roman B, et al. Clinical practice guideline: Evaluation of the neck mass in adults. Otolaryngol Head Neck Surg 2017;157(2_suppl):S1–30. doi: 10.1177/0194599817722550