Progressive increase of human papillomavirus carriage rates in potentially malignant and malignant oral disorders with increasing malignant potential

Introduction:  We investigated the potential role of human papillomaviruses (HPVs) in potentially malignant oral disorders, oral leukoplakia (OL) and oral lichen planus (OLP), and in oral squamous cell cancer (OSCC) in an Eastern Hungarian population with a high incidence of OSCC.
Methods:  Excised tumor samples (65 OSCC patients) and exfoliated cells from potentially malignant lesions (from 44 and 119 patients with OL and OLP, respectively) as well as from healthy controls (72 individuals) were analysed. OLPs were classified based on clinical appearance, 61 patients had erosive–atrophic lesions (associated with higher malignancy risk, EA-OLP) and 58 had non-erosive non-atrophic lesions (with lower risk of becoming malignant, non-EA-OLP), respectively. Exfoliated cells collected from apparently healthy mucosa accompanied each lesion sample. HPV was detected by MY/GP polymerase chain reaction (PCR) and genotyped by restriction analysis of amplimers. Copy numbers in lesions were determined using real-time PCR. Prevalence rates, copy number distributions, and association with risk factors and diseases were analysed using chi-square test, t -test, and logistic regression, respectively.
Results:  We detected HPVs significantly more frequently in lesions than in controls ( P  ≤ 0.001 in all comparisons). HPV prevalence increased gradually with increasing severity of lesions (32.8, 40.9, and 47.7% in OLP, OL, and OSCC, respectively). Copy number distribution patterns roughly corresponded to prevalence rates, but OLP and OL were comparable. HPV prevalence differed significantly between EA-OLP and non-EA-OLP groups (42.6 vs. 22.4%); EA-OLP group showed a prevalence similar to that found in OL.
Conclusion:  HPVs may be involved in the development or progression of not only OSCC but also of potentially malignant oral lesions.     

人乳头瘤病毒和人巨细胞病毒与口腔癌的关系

目的：检测口腔白斑和口腔鳞状细胞癌中的人乳头瘤病毒（HPV16）DNA和人巨细胞病毒（HCMV）DNA,探讨HPV16和HCMV与口腔癌之间的关系。方法：应用多聚酶链反应（PCR）技术扩增HPV16DNA和HCMVDNA,采用2%琼脂糖凝胶电泳分析,检测口腔白斑和口腔鳞状细胞癌中的HPV16DNA和HCMVDNA。结果：6例口腔白斑中,HPV16DNA的阳性率为16.7%,HCMVDNA为16.7%,16例口腔鳞癌组织HPV16DNA的阳性率为31.3%,HCMVDNA为25%,例正常组织均未检测出。结论：4HCMV与HPV16在口腔癌的发生中具有协同致癌作用。     

A comparison of the management of potentially malignant oral mucosal lesions by oral medicine practitioners and oral & maxillofacial surgeons in the UK

This study describes the results of a survey undertaken to assess the management of potentially malignant oral mucosal lesions by oral medicine practitioners and compares their approach with that of oral & maxillofacial surgeons that we have previously described. Significant differences were noted between the two groups in the use of photography to document the lesions and in the use of certain special investigations, which included measurement of serum iron, serum ferritin, serum Vit B12, red cell folate and candidal isolation. The groups also varied in the perceived importance of the age of the patient and anatomical site of the lesion when deciding on the need for further biopsy. There was also significant variation in the use of certain treatment modalities, including excising non-dysplastic and severely dysplastic/carcinoma in-situ lesions and eliminating trauma when treating mild/moderately dysplastic and severely dysplastic/carcinoma in-situ lesions. Significant differences in the frequency and duration of follow-up were noted for non-dysplastic lesions. Finally, the two groups differed significantly when asked to rank the perceived importance of certain factors (the histopathology of the most recent biopsy and the anatomical site of the lesion) when deciding the need to follow-up. Possible reasons for the variation are discussed.     

Highly sensitive detection of HPV-DNA in paraffin sections of human oral carcinomas

BACKGROUND: Although human papillomavirus (HPV) infection has been shown to be a significant carcinogen in cervical squamous cell carcinoma (SCC), its significance in oral SCC remains unclear. METHODS: We developed highly sensitive detection methods for HPV to elucidate the prevalence and localization of HPV in paraffin sections from human oral SCC using modified in situ polymerase chain reaction (PCR) and in situ hybridization AT tailing (ISH-AT). Analyses revealed a high prevalence of several HPV types (HPV-16, -18, -22, -38 and -70) under optimal conditions. The ISH-AT method can be used as an alternative to in situ PCR. RESULTS: Various staining patterns were observed in the 20 cases examined, and HPV-positive cells were localized within the surface epithelium as well as in neoplastic cells. We demonstrated that HPV-DNA could be detected in paraffin sections using either the method of in situ PCR or ISH, providing an appropriate primer and probe are used. CONCLUSION: These results suggest that HPV infection could be one of several risk factors being involved in oral SCC.     

Human papillomavirus infection in oral potentially malignant disorders and cancer

Human papillomavirus (HPV) infects keratinocytes in the mucosa or skin, and persistent infection with HPV may lead to premalignant lesions and invasive cancer, especially cervical cancer. It has also been hypothesized that HPV infection is an etiological factor of oral squamous cell carcinoma and oral precancerous disorders such as lichen planus, leukoplakia, and erythroplakia. A high percentage of HPV in oral lesions supports the possible viral contribution, but an association of HPV infection with these lesions remains to be established. The current paper will update the latest progress of HPV infection in several oral potentially malignant disorders and oral squamous cell carcinoma and discuss the impact of HPV infection on the progression of oral potentially malignant disorders.     

口腔鳞状细胞癌及白斑人乳头瘤病毒16型感染的临床研究

目的:探讨口腔鳞状细胞癌(OSCC)和白斑(LK)患者人乳头瘤病毒16型(HPV-16)感染和临床病理参数之间的相关性。方法:收集30例OSCC和5例LK患者的组织切片,所有病例均经病理学确诊,提取组织DNA,通过巢式PCR检测HPV-16感染情况。结果:HPV-16与TNM分级之间未见相关性,60岁以下女性患者的HPV-16感染率高于60岁以上女性患者(P=0.024),而男性患者未见HPV-16感染和年龄存在相关性(P=0.649)。结论:60岁以下女性OSCC及LK患者中出现较高的HPV-16感染率,提示这可能是新的致癌危险因子。     

Aberrant glycosylation in oral malignant and premalignant lesions

Cell surface carbohydrates serve as differentiation and developmental markers characteristic of different cell and tissue types. The expression of these carbohydrate antigens is often significantly altered in tumors, particularly in those arising from epithelial tissues. Analysis of cell surface carbohydrates in oral epithelium have shown that in normal epithelium they are expressed in a way that shorter carbohydrates are found on basal cells and that these carbohydrate structures are elongated parallel to terminal differentiation. The carbohydrate expression is altered in oral carcinomas and in some oral premalignant lesions. The change in carbohydrate expression can at present be explained by the lack of synthesis of specific glycosyltransferases. We have found mosaicism in the expression of carbohydrate antigens in all tumors and have found that the expression of a specific carbohydrate in the deep invasive parts of the tumor correlates with tumor prognosis.     

Expression of p16 in oral cancer and premalignant lesions

Background:  Expression of p16 has been proposed as a marker for malignant transformation. This study aimed to evaluate p16 expression in oral squamous cell carcinoma (OSCC) and premalignant lesions including oral leukoplakia (OL) with and without dysplasia.
Methods:  Expression of p16 was investigated in 56 samples including OSCC, OL with and without dysplasia, and normal oral mucosa. Expression of p16 was identified by immunohistochemistry, using the CINtecTM p16INK4a Histology Kit. Both nuclear and/or cytoplasmic staining of the keratinocytes were considered to be positive and the percentage of positive cells was calculated.
Results:  Expression of p16 was detected in 3/16 (18.75%) cases of OSCC, in 4/15 (26.7%) cases of OL without dysplasia, and in none of OL with dysplasia and normal mucosa. No significant differences in p16 expression prevalence were found among OSCC, OL with and without dysplasia and normal mucosa. The percentages of positive cells in OSCC and OL without dysplasia were 0.89 and 0.17, respectively. No significant difference in the percentage of positive keratinocytes was found.
Conclusion:  As a marker, p16 is not reliable for oral mucosal dysplasia and malignant transformation.     

Role of human papillomavirus infection in carcinogenesis of oral squamous cell carcinoma with evidences of prognostic association

J Oral Pathol Med (2012) 41 : 9–15 Background: Betel nut chewing, cigarette smoking and alcohol drinking are thought to be major environmental risk factors responsible for the development of oral squamous cell carcinomas. Oncogenic human papillomavirus infections have a well‐established association with uterine cervical carcinoma. However, little is known about the exact role of human papillomavirus infections in oral squamous cell carcinomas. This study is designed to elucidate the role of human papillomavirus infections in cancer development and prognosis of oral squamous cell carcinomas. Methods: Molecular techniques including in situ hybridization and immunohistochemistry of p16^INK4A and p53 for evidences of human papillomavirus in tissue micro‐arrays were investigated. Results: Twenty‐four of 65 cases of oral squamous cell carcinomas were found positive for in situ hybridization and 14 were found positive for p16^INK4A. The majority of cases without the evidence of human papillomavirus were related to p53 over‐expression. There were statistically significant correlations between the results of human papillomavirus test and size or extent of the tumor (P = 0.003) or the stage of oral squamous cell carcinomas (P = 0.015). Kaplan–Meier plot analysis demonstrated a tendency of longer survival in cases of oral squamous cell carcinomas with the evidence of human papillomavirus or positive p16 ^INK4A. Conclusions: Human papillomavirus infections may play a unique role in oral carcinogenesis. Our data strongly suggest that human papillomavirus‐positive oral squamous cell carcinomas comprise a distinct clinical and pathological disease entity that appears related to a better outcome with longer survival and bears a causally associated relationship different from other carcinogenic mechanisms.     

Potentially malignant oral lesions in Northern Ireland: size (extent) matters

OBJECTIVES: We examined clinical parameters of patients from Northern Ireland with potentially malignant lesions (PML) to determine association with development of intraoral squamous cell carcinoma (SCC). DESIGN: retrospective, cross-sectional, population-based, clinically validated, laboratory-verified. SUBJECTS AND METHODS: All patients who had more than one incisional oral mucosal biopsy diagnosed from 1975-1991 were abstracted from a database of all PML and SCC and their clinical records and biopsies reviewed. Patients were excluded if there was priorlsynchronous SCC or radiotherapy, frictional keratosis or lichen planus, missing clinical records/biopsy material or follow-up of <24 months. From the 50 suitable patients, gender, age, smoking status, site, clinical appearance and extent of lesion(s), treatment and year of diagnosis were recorded. Patients who developed SCC from PML were compared with those who did not. RESULTS: Squamous cell carcinoma occurred significantly more often in patients with single rather than multiple PML, those with 'non-homogenous' PML and in patients diagnosed prior to 1980. In Cox's survival analysis, only the clinical extent was predictive of SCC. CONCLUSIONS: Of all the features considered in our series, size (extent) was the most important clinical factor in determining the risk of future SCC in PML, particularly when several adjacent anatomical sites were affected.     

Potentially malignant oral lesions in northern Ireland: a 20-year population-based perspective of malignant transformation

This retrospective laboratory-based study investigates the potential for malignant transformation of oral mucosal lesions in a population of 1.6 million. Over the 20-year period there were 745 patients diagnosed with primary intra-oral squamous cell carcinoma (OSCC), 165 patients with dysplasia and 1182 patients with 'non-dysplastic' lesions (epithelial hyperplasia, hyperkeratosis epithelial atrophy, lichen planus and lupus erythematosus). Malignant transformation occurred in 15% of dysplasias and in 1% of 'non-dysplastic' lesions at average intervals after diagnosis of 48 and 65 months respectively. Only 6% of patients with OSCC had a pre-invasive lesion biopsied. These data suggest that white lesions are only rarely the pre-invasive phase of OSCC. It is possible therefore that early changes are red, small or even microscopic with carcinoma developing without a clinically observable phase. More effective management strategies will require the development of tissue markers to enhance early detection.