The characteristics of human papillomavirus DNA in head and neck cancers and papillomas

Abstract

Aim: To determine the prevalence, type, physical state, and viral load of human papillomavirus (HPV) DNA in cases of head and neck cancer and recurrent respiratory papillomatosis (RRP). Methods: The prevalence and type of HPV DNA was determined in 27 fresh frozen tissue specimens from patients with head and neck cancers and 16 specimens from 10 patients with RRP by MY09/MY11 and GP5+/ GP6+ nested polymerase chain reaction (PCR) and subsequent restriction enzyme cleavage. The physical state of HPV DNA was analysed by E1, E2, and E1E2 specific PCRs and Southern blot hybridisation (SBH). Results: HPV DNA was detected in 13 of 27 cancers and 10 of 10 papillomas. Both low risk HPV-6 and HPV-11 and high risk HPV-16 were present in cancers in low copy numbers, whereas papillomas exclusively harboured low risk HPV-6 and HPV-11. E1E2 PCRs failed to determine the physical state of HPV in cancers except one case where HPV-6 DNA was integrated. In contrast to cancers, all papillomas showed the episomal state of HPV DNA and a relatively higher viral load. Conclusions: Based on the prevalence, type, physical state, and copy number of HPV DNA, cancers and papillomas tend to show a different HPV DNA profile. The 100% positivity rate of low risk HPV types confirms the role of HPV-6 and HPV-11 in the aetiology of RRP.T he association of high risk human papillomavirus (HPV) types with anogenital cancers is well established. In the past two decades, several authors have detected HPV DNA in head and neck cancers by Southern blot hybridisation (SBH) or polymerase chain reaction (PCR).1-10 Among head and neck cancers, HPV DNA positivity tends to show site dependence, with the tonsils, oral cavity, and larynx being the most common sites.1 7 10 High risk HPV types 16 and 18 are by far the most predominant types at all sites.3 7 10 11 However, epidemiological data reveal that the role of HPVs in the aetiology of head and neck cancers is rather controversial: the reported frequency of HPV DNA even in the often studied laryngeal site varies between 3% and 85% in the literature. 8 In addition, the prognostic value of HPV DNA positivity is also equivocal. Recurrent respiratory papillomatosis (RRP) is the most common benign tumour of the laryngeal epithelium.12 Low risk HPV-6 and HPV-11 are the most frequently detected types and are accepted as aetiological agents in RRP. [13][14][15][16] ''The product of the E2 open reading frame has a regulatory role in the transcription of the transforming E6 and E7 viral genes'' HPV DNA may exist either in the episomal form or integrated into the host's genome. [17][18][19][20] In the episomal form, the circular double stranded papillomavirus DNA is intact. In contrast, integration results in disruption of the circular viral genome, mainly in the E1E2 open reading frames (ORFs). 21The product of the E2 ORF has a regulatory role in the transcription of the transforming E6 and E7 viral genes. Disruption of this regulatory role at integration results in increased concentrations of transforming viral proteins...

Oral squamous papilloma: clinical, histologic and immunohistochemical analyses

“…Of the 14 papillomas evaluated by Fregonesi et al (14) using in situ hybridization, 14% (2) were positive for HPV 6/11, 22% (n = 3) were positive for HPV 16/18, and the great majority (64%, 9) were negative for HPV. However, Major et al (16) found 100% PCR positivity for HPV 6 or HPV 11 DNA in 10 papillomas due to recurrent respiratory papillomatosis. Generally, in children with laryngeal papillomatosis, there can be coinfection by HPVs 6 and 11.…”

Squamous Papilloma: Case Report and Review of Literature

“…The squamous papilloma is associated with human papilloma virus (HPV) types 6, and 11 (Major et al, 2005). Oral squamous papilloma, including the vermilion portion of the lip, is the most common papillary lesion of the oral mucosa and makes up approximately 2.5% of all oral lesions.…”

Human Papillomavirus in Non-Oropharyngeal Head and Neck Cancers: A Systematic Literature Review

“…Compared to oral carcinomas, a greater diversity of other HPV types has been detected: HPV18, HPV26, HPV31, HPV33, HPV39, HPV36, HPV45, HPV51, HPV52, HPV58, HPV59, HPV66, and HPV69 [8,9,14,20,26,29,39,65,71,90,94]. Low-risk HPV are uncommonly detected, and might represent incidental ''bystander'' rather than possibly ''driver'' infection [29,39,65,75,90,94].…”