Table 3.

UK/US treatment recommendations for HPV⁺ OPSCC (not yet updated for AJCC 8th edition staging guidelines)

Approach	Early stage (T1 or T2 N0)	Late stage (T3 or T4 N0; T1–4 N1–3)
Open surgery
PM Mandibulectomy TCP G/LR	Not typically recommended; TORS/TLM resection or definitive RT instead	Usually, PM or TCP for tongue base resections, G/LR not frequently used; mandibulectomy for tumours with gross bony involvement Lip-splitting mandibulotomy usually required for adequate visualization Reconstruction by radial artery free or anterolateral thigh free flaps Also used when surgical salvage is required Adjuvant CRT or PORT usually required Modified or selective neck dissection recommended
Transoral surgery
TORS TLM	T1/T2, potentially T3; ipsilateral selective neck dissection recommended, N0 treated electively Adjuvant RT/CRT to reduce risk of recurrence depending on tumour features	Limited to early stage disease
Definitive RT
Radical (70 Gy/35 fractions); hypofractionated (65–66 Gy/30 fractions) Intensity modulated	Usually restricted to patients with no previous history of head and neck irradiation and/or those with substantial comorbidities Prophylactic RT to ipsilateral cervical lymph nodes for lateralized tumours, both sides for non-lateralized tumours Cetuximab might be a safer alternative for patients with pre-existing sensorineural hearing loss or renal, cardiac or haematological impairments	Only if patient is unfit for CRT (such as those >70 years of age, and/or with poor performance status)
	In clinical trials for de-escalation in definitive and adjuvant settings
Definitive CRT
70 Gy RT (2 Gy fractions) with concurrent cisplatin (either 100 mg/m2 on days 1, 22 and 43 of RT or 40 mg/m2 weekly)	Usually, restricted to patients for whom surgery is either not indicated or who wish to avoid surgery owing to patient preference	Technical feasibility for surgery is dictated by evidence of extratonsillar disease involvement, which might require reconstruction of the defect or lateral disease located close to the carotid artery or advanced bilateral nodal disease
Adjuvant therapy
CRT comprising 70 Gy RT (delivered as 2 Gy fractions) with concurrent cisplatin (either 100 mg/m2 on days 1, 22 and 43 of RT or 40 mg/m2 weekly) PORT comprising 70 Gy RT (delivered as 2 Gy fractions)	For positive or close resection margins or extranodal extension of lymph nodes; or other high-risk features (lymphovascular or perineural invasion) PORT can be with or without concurrent chemotherapy	Improves outcomes for patients with extracapsular invasion and/or microscopically involved surgical resection margins around the primary tumour Not recommended for those >70 years of age and/or those with poor performance status

See refs^155,245. AJCC, American Joint Committee on Cancer; CRT, chemoradiotherapy; G/LR, glossotomy/lingual release; HPV, human papillomavirus; OPSCC, oropharyngeal squamous cell carcinoma; PM, paramedian mandibulotomy; PORT, post-operative radiotherapy; RT, radiotherapy; TCP, trans-cervical paryngotomy; TLM, transoral laser microdissection; TORS, transoral robotic surgery.