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Clinico-pathological characterisation of human papillomavirus-associated oral epithelial dysplasia

Thavaraj S, Henley-Smith R, Gregson-Williams H, Yogarajah S, Odell EW, Sathasivam H

Oral Oncol, 2025 Mar;162:107182.
PMID: 39874724 DOI: 10.1016/j.oraloncology.2025.107182

BACKGROUND: Human papillomavirus-associated oral epithelial dysplasia (HPV-OED) has been recently recognised by the World Health Organisation (WHO) as a distinct type of oral epithelial dysplasia. The rarity of HPV-OED, together with gaps in the current understanding of risk factors and clinical behaviour raise the risk of under-recognition and misdiagnosis. To address this, we describe the clinico-pathological features of a consecutive series of HPV-OED from a single institution to provide additional insight into the presentation and behaviour of this disease.
METHODS: Consecutive cases of HPV-OED were identified over a 20-year period from the pathology routine diagnostic archives of a single centre. Cases with features of viral cytopathic changes in a background of OED underwent HPV-specific testing in addition to p16 immunohistochemistry to confirm HPV positivity.
RESULTS: Fifty-three consecutive patients with HPV-OED were identified. The mean age at diagnosis was 55 years-old and there was a strong male predilection (83 %). Most patients were smokers or former smokers, and almost a fifth of individuals were Human Immunodeficiency Virus (HIV)-positive. The latero-ventral tongue was the most common index site. Twenty-eight percent of cases were associated with invasive oral squamous cell carcinoma. There was a statistically significant association between with patient's HIV status and malignant transformation (p = 0.022).
CONCLUSIONS: Findings from our cohort of HPV-OED patients suggests that malignant transformation is relatively frequent and associated with the HIV status of patients.

Matched MeSH terms: Precancerous Conditions/virology
Biological properties of TW01 cells expressing latent membrane protein-1 gene of EBV-derived from nasopharyngeal carcinoma cells at different stages of malignancy

Tan EL, Sam CK

Exp Oncol, 2007 Sep;29(3):166-74.
PMID: 18004239

Epstein-Barr virus (EBV), a human gammaherpesvirus is intimately associated with nasopharyngeal carcinoma (NPC), with the incidence of the virus detected in malignant tissues being close to 100% in NPC endemic areas. The viral latent gene, latent membrane protein 1 (LMP1), has all the typical characteristics of an oncogene and extensive studies have shown beyond doubt its abilities in cellular transformation giving rise to malignant phenotypes. The present study compares the gene sequence and biological properties of LMP1 gene derived from two patients with different stages of NPC--one presented with dysplastic, pre-malignant lesion and the other with malignant lesion.

Matched MeSH terms: Precancerous Conditions/virology*
Fulltext Clonal proliferations of cells infected with Epstein-Barr virus in preinvasive lesions related to nasopharyngeal carcinoma

Pathmanathan R, Prasad U, Sadler R, Flynn K, Raab-Traub N

N Engl J Med, 1995 Sep 14;333(11):693-8.
PMID: 7637746 DOI: 10.1056/NEJM199509143331103

BACKGROUND: The Epstein-Barr virus (EBV) is consistently detected in patients with nasopharyngeal carcinoma. To determine whether EBV infection is an early, initiating event in the development of this malignant tumor, we screened nasopharyngeal-biopsy samples, most of which were archival, for preinvasive lesions, including dysplasia and carcinoma in situ. Preinvasive lesions were found in 11 samples, which were tested for the presence of EBV.
METHODS: EBV infection was detected with in situ hybridization for EBV-encoded RNAs (EBERs) and by immunohistochemical staining for latent membrane protein 1 (LMP-1). The larger samples were also tested for the EBV genome with the use of Southern blotting. The expression of specific EBV RNAs was determined by the amplification of complementary DNA with the polymerase chain reaction.
RESULTS: Evidence of EBV infection was detected in all 11 tissue samples with dysplasia or carcinoma in situ. EBERs were identified in all eight samples tested, and LMP-1 was detected in all six of the tested samples. Six of the seven samples tested for the EBV termini contained clonal EBV DNA: Transcription of the latent EBV gene products, EBV nuclear antigen 1, LMP-1, LMP-2A, and the BamHI-A fragment, was detected in most of the samples. Viral proteins characteristic of lytic lesions were not detected.
CONCLUSIONS: Preinvasive lesions of the nasopharynx are infected with EBV. The EBV DNA is clonal, indicating that the lesions represent a focal cellular growth that arose from a single EBV-infected cell and that EBV infection is an early, possibly initiating event in the development of nasopharyngeal carcinoma. Preinvasive lesions contain EBV RNAs that are characteristic of latent infection but not the viral proteins that are characteristic of lytic infection. The detection of the EBV-transforming gene, LMP-1, in all the neoplastic cells suggests that its expression is essential for preinvasive epithelial proliferations associated with nasopharyngeal carcinoma.

Matched MeSH terms: Precancerous Conditions/virology*

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