Human papillomavirus: Its identikit and controversial role in oral oncogenesis, premalignant and malignant lesions (Review)

Abstract

Human papillomaviruses (HPVs) are a group of host-specific DNA viruses, with a remarkable epithelial cell specificity: they have been reported principally in the anogenital tract, urethra, skin, larynx, tracheo-bronchial and oral mucosa. More than 100 different HPV types have been identified and classified as high (e.g. 16, 18, 31) or low (e.g. 11, 42, 36)-risk (HR and LR), based on their association with cervical carcinoma. The carcinogenic role of HR-HPV revolves mainly around two of its oncoproteins: HPV-E6 which promotes degradation of the p53 tumour suppressor gene product and HPV-E7 which modifies the pRb tumour suppressor gene product, inhibiting the activity of TGF-ß2. Since these viral oncoproteins are capable of transforming primary human keratinocytes from either genital or upper respiratory tract epithelia, they have been considered to play a role in disrupting cell-cycle regulatory pathways leading to a genetic progression to ano-genital cancer and, possibly, also to oral squamous cell carcinoma (OSCC). Recently, the oncogene HPV-E5 has also been found to transform cells by modulating growth factor receptors. On the basis of the high, although very variable, frequency of HR-HPV in OSCC, an oral malignant potential of HPV infection has been hypothesised but not definitively confirmed. Major aims of this review are to update the understanding of HPV activities with respect to oral oncology and to comment on the HPV DNA reported frequencies in OSCC and potentially malignant oral lesions. A computer database search was performed, through the use of MEDLINE (PubMED) and Cochrane Library, for the last three decades. Search key words used were: human papillomavirus, HPV and cancer, HPV and oral lesions, HPV and oral premalignant lesions, HPV and oral cancer, HPV and HNSCC, HPV and oral mucosa. The search was of all fields, all languages and all dates available. Contents 1. Human papillomavirus: identikit of a virus 2. HPV and oral oncology 3. Conclusions

Correlation between koilocytes and human papillomavirus detection by PCR in oral and oropharynx squamous cell carcinoma biopsies

“…One metaanalysis study observed that the prevalence of HPV was higher in carcinomas of the oropharynx (38.1%) than in carcinomas of the mouth, pharynx and larynx (24.1%) (Termine et al 2008). Conversely, in our study, HPV prevalence was higher (33.7%) and more consistent with data from mouth, pharynx and larynx squamous cell carcinoma (34.5%) studies that used PCR methods, as reported in a recent review by Campisi et al (2007). The use of fresh tissue will increase the detection rate due to better quality of DNA material, but paraffin-embedded materials allow for retrospective study.…”

Presence of HPV DNA in convalescent salivary rinses is an adverse prognostic marker in head and neck squamous cell carcinoma

“…5 High risk HPVs have been demonstrated to be involved in epithelial carcinogenesis. HPV is found in both premalignant and malignant tumors.…”

Low prevalence of human papillomavirus in squamous-cell carcinoma limited to oral cavity proper

“…10,12,13 The wide range of prevalence could be related to (1) the distribution of the human papillomavirus among the population, (2) oral sexual behavior, (3) the sampling strategy used (gross specimens, cotton swaps or mouthwash) [14][15][16][17] and (4) the detection method (polymerase chain reaction, quantitative polymerase chain reaction, enzyme-linked immunosorbent assay and immunohistochemistry). 18,19 In addition, random fluctuations due to limited-sized sampling have exacerbated variability. 20 To detect whether the human papillomavirus might have a role in the onset of squamous-cell carcinoma limited to oral cavity proper, a large series of fresh and paraffin-embedded tumor specimens with pair-matched controls were analyzed by means of quantitative polymerase chain reactions and the results verified with immunohistochemistry.…”