The aetiology of squamous cell carcinomas of the head and neck (HNSCC) is multifactorial. Oncogenic human papillomaviruses (HPVs), a causative agent in uterine cervical cancer, have also been repeatedly detected in HNSCC, especially in squamous cell carcinomas of tonsils. Approximately half the HPV DNA-positive HNSCC contain detectable E6/E7 transcripts with wild-type p53, reduced pRb and overexpressed p16 in the tumours. HPV-16 is the predominant type and exists in episomal, integrated, or mixed forms. Tonsillar carcinomas have a remarkably higher viral load than carcinomas at other sites of the head and neck region. HPV-16 DNA has also been detected in tumour-free tonsils. Infection by oncogenic HPVs is a necessary but not a sufficient cause of cancers. Studies on the molecular mechanisms underlying HPV-associated carcinogenesis are difficult, because HPV is not easy to propagate in vitro. HPV-immortalised human tonsillar epithelial cell lines may provide an in vitro model to study co-factors for the HPV-associated tonsillar cancers and to test the effects of anti-viral and anti-tumour agents. Copyright © 2005 John Wiley & Sons, Ltd.