Fig. 1. Incidence, anatomical locations and histological appearance of HPV⁺ oropharyngeal cancers.

a | Directly age-standardized rates per 100,000 population of newly diagnosed cases of cervical and oropharyngeal cancer in the UK and the USA. For male oropharyngeal cancers (pink dotted line) and cervical cancers (pink solid line) in the UK from 1995 to 2016, data are sourced from the UK Office for National Statistics cancer data²⁴¹. Male oropharyngeal cancers include those of the base of tongue, uvula, tonsil and oropharynx, stratified for different types of squamous cell carcinoma (SCC) (as for the US data). Observed age-standardized rates per 100,000 population of newly diagnosed cases of cancer; for oropharyngeal cancers among men (yellow dotted line) and cervical cancers (yellow solid line) from 1995 to 2014 obtained from registries within the Surveillance, Epidemiology, and End Results (SEER) programme²⁴². Oropharyngeal cancers included those of the base of tongue, lingual tonsil, soft palate not otherwise specified, uvula, tonsil, oropharynx and Waldeyer’s ring. Cervical cancers include all histological subtypes. b | Basic anatomy of the oropharynx, with inset images from top to bottom depicting human papillomavirus-positive oropharyngeal squamous cell carcinoma (HPV⁺ OPSCC) located at the base of tongue (the anterior two-thirds), the soft palate and the tonsil. c | Histological appearance, clockwise from top left. i | Non-keratinizing SCC. ii | Non-keratinizing SCC with immunohistochemical staining for p16; morphology is monomorphic, ovoid, hyperchromatic with inconspicuous cytoplasm. This sample also features increased mitosis, apoptosis and comedo-type necrosis. iii | Keratinizing SCC, featuring filiform projections, a thickened, nonmalignant-appearing stratified squamous epithelium, hyperparakeratosis and keratin plugging. iv | Basaloid SCC featuring variable foci of squamous differentiation. v | Papillary SCC with early invasion, featuring predominant filiform processes with minimal or absent keratinization, frequent mitosis and full-thickness dysplasia with a basaloid cell morphology. vi | Spindle-cell carcinoma, featuring a biphasic tumour composed of SCC and malignant spindle-cell component, exhibits polypoid growth. All images in c shown at 40× magnification.