The aim of our study was to investigate the physical state and the viral load of HPV‐16 in tonsillar cancer and to correlate these findings with clinical outcome. To distinguish between integrated and episomal forms of HPV, 22 fresh‐frozen tonsillar cancer samples were analysed by a method based on restriction enzyme cleavage, ligation and PCR (rliPCR). HPV‐16 was detected in 11/22 and HPV‐33 in 1/22 of the cancers, hence 12/22 (55%) of the tumours were HPV positive. Only extrachromosomal forms of HPV‐16 were observed. Full‐length episomal HPV was detected exclusively in 7/11 of the cancers, whereas both full‐length and deleted forms of episomal HPV‐16 were found in parallel in 2 other tumours. In 1 tumour only a deleted episomal form of HPV‐16 was present. In the remaining HPV‐16 positive tumour both full‐length episomal as well as an 11 kbp PCR product were detected and if the 11 kbp product contained integrated HPV, or was off‐size linearised episomal could not be determined. In 2 cervical cancer controls, HPV‐16 was integrated and could be chromosome located. HPV‐16 was quantified by real‐time PCR and most tonsillar cancers contained between 10 to a few hundred copies of HPV per β‐actin. The 6 patients with tumour sections with ≥190 HPV‐16 copies/β‐actin remained tumour free (p = 0.026) and had a better survival rate (p = 0.039) when compared to the 5 patients with tumours sections with ≤60 HPV‐16 copies/β‐actin. In conclusion, HPV‐16 is mainly episomal in tonsillar cancer. The viral load showed a wide distribution and the clinical outcome in our study was better when the HPV load was higher. © 2002 Wiley‐Liss, Inc.