Dean K. White

Human papillomavirus expression in oral mucosa, premalignant conditions, and squamous cell carcinoma: A retrospective review of the literature**

OBJECTIVES The literature of human papillomavirus detection in normal oral mucosa and oral lesions associated with the dysplastic progression of epithelium was reviewed to help define the role of this virus in the development of oral squamous cell carcinoma. STUDY DESIGN All available data from published studies were analyzed by chi-square test for association between the human papillomavirus and age, gender, race, DNA type, location, lesional dysplastic progression, method of detection, tissue preservation, and use of tobacco and alcohol. RESULTS Human papillomavirus was identified with increasing frequency in normal oral mucosa (13.5%), benign leukoplakia (14.8%), intraepithelial neoplasia (18.5%), squamous carcinoma (26.2%), and verrucous carcinoma (27%). It was detected in oral squamous cell carcinoma significantly (p < 0.005) more often (37.1%; 122 of 329) in studies that used a high sensitivity assay (polymerase chain reaction) than studies that used moderate sensitivity assays (25.2%; 84 of 334) (e.g., Southern blot hybridization) and low sensitivity assays (16.9%; 61 of 362) (e.g., immunohistochemistry, in situ hybridization). Human papillomavirus DNA was detected significantly more often (p < 0.001) in frozen oral squamous cell carcinoma (51.6%; 115 of 223) than paraffin-embedded tissue (21.7%; 136 of 628). High-risk human papillomaviruses (2, 16, 18) were detected in 81.4% of OSCCs that contained the virus compared with low-risk human papillomavirus genotypes (6, 11) in 17.9% of oral squamous cell carcinoma that contained the human papillomavirus (p < 0.001). In studies that analyzed the use of chemical cofactors, the use of tobacco and alcohol (87.3%) was associated more often with oral squamous cell carcinoma than the presence of human papillomavirus (51.3%), however, the difference was not significant. CONCLUSION High-risk human papillomavirus genotypes have a significant association with oral squamous cell carcinoma. However, the presence of this virus in a high proportion of oral normal mucosa makes the virus alone a poor prognosticator of progression to malignancy.

In situ hybridization analysis of human papillomavirus DNA in oral mucosal lesions

Commercial biotinylated DNA probes specific for human papillomavirus (HPV) types 6 and 11; 16 and 18; and 31, 33, and 35 were used for in situ hybridization analysis of 105 oral mucosal specimens from 5 cases of verruca vulgaris, 15 cases of condyloma acuminatum, 30 cases of squamous papilloma, 20 cases of hyperkeratosis/acanthosis, 15 cases of epithelial dysplasia, 5 cases of carcinoma in situ, and 15 cases of squamous cell carcinoma. Positive hybridization signals were found in 26 specimens (24.8%). Only HPV-6/11 was detected. HPV DNA occurred significantly more often (p less than 0.005, chi-square analysis) in condyloma acuminatum (100%) and verruca vulgaris (100%) than squamous papilloma (13.3%), hyperkeratotic/acanthotic lesions (10%), and malignant and premalignant lesions (0%). The tongue (19.1%) and labial epithelium (17.1%) were infected most frequently. Nuclear reaction products indicating HPV infection were associated primarily with koilocytes. These results demonstrate the usefulness of commercial biotinylated probes for HPV DNA analysis in routine paraffin-embedded lesion specimens. They confirm HPV involvement in benign lesions of the oral mucosa but fail to associate HPV infection with oral cancer and precancer.

Combined epithelial odontogenic tumor: Adenomatoid odontogenic tumor and calcifying epithelial odontogenic tumor

1. Two cases of a combined epithelial odontogenic tumor which had areas of AOT and CEOT were presented. 2. A review of the studies on histogenesis of the AOT revealed that the tumor probably consists of preameloblasts, stratum intermedium, and stellate reticulum. 3. A review of the studies on histogenesis of the CEOT revealed that the probable origin was in cells of stratum intermedium. 4. It is suggested that the present cases support the aforementioned theories of histogenesis and represent AOTs which contain foci of CEOT. 5. The suggested treatment is simple surgical excision.

Detection of HPV DNA in oral carcinoma using polymerase chain reaction together with in situ hybridization

This study determined the prevalence of human papillomavirus 16/18 DNA in deparaffinized oral carcinoma specimens on slides with the use of the different sensitivities of in situ hybridization and a technique that combines polymerase chain reaction and in situ hybridization. Human papillomavirus DNA was not detected in the 30 biopsy specimens analyzed by in situ hybridization alone using biotinylated DNA probes specific for human papillomavirus 16/18. Twenty of 30 specimens (66.7%) were found to have human papillomavirus DNA (p < 0.001) with the use of the polymerase chain reaction-in situ hybridization technique. Human papillomavirus 16 was detected in 18 of 26 specimens (69.2%), and 7 of 25 carcinomas (28%) were found to contain human papillomavirus 18. Dual infections were present in 5 of 21 (23.8%) specimens. Human papillomavirus DNA was more prevalent in men (75%) than women (57.1%). However, there was no difference in the mean age of patients with oral carcinoma (men, 67.8 years; women, 67.5 years) who had human papillomavirus and those who did not (67.2 years). Carcinomas associated with dual infections occurred at a lower mean age (59.4 years) than those associated with a single human papillomavirus type (p < 0.005). We conclude that the polymerase chain reaction-in situ hybridization technique enhances our ability to demonstrate human papillomavirus types highly associated with oral squamous cell carcinoma.

Verruciform xanthoma within carcinoma in situ

This report describes an unusual case of verruciform xanthoma of the posterior floor of the mouth that occurred within carcinoma in situ. The significance of this case is described in light of current theories on the etiology and management of verruciform xanthoma.

Dentinal candidiasis in cancer patients.

Two examples of an unusual presentation of oropharyngeal candidiasis in cancer patients are offered. The light and scanning electron microscopic appearances of candidiasis involving the dentin of teeth are described. The potential significance of recognition of this form of candidiasis in cancer patients is discussed.

Intraneural perineurioma--not restricted to major nerves.

The intraneural perineurioma is an uncommon proliferation of perineural cells that forms onion bulb-like structures surrounding the nerve axons within a portion of a single affected nerve. The etiology is idiopathic, and it is controversial whether the process is reactive or neoplastic. All previously reported cases have involved major nerves and have been associated with motor deficits and, less frequently, sensory signs or symptoms. The current case represents the first example shown to arise in a small unnamed nerve before the development of clinically detectable nerve dysfunction. The process appears to be progressive; and when detected in a small nerve, excision is recommended to prevent proximal extension and possible development of motor or sensory deficits.

Intraosseous fibrous lesions of the jawsA manifestation of tuberous sclerosis

Four patients previously diagnosed with tuberous sclerosis are reported with intraosseous fibrous lesions of the jaws. Review of the literature revealed comparable pathosis occurring in extragnathic bones and several previous reports of similar lesions within the jaws. Therefore, these intraosseous fibrous proliferations are thought to represent an intraoral manifestation of tuberous sclerosis and not coincidental findings. In all 4 cases, the tumors demonstrated significant collagenization with numerous interspersed plump fibroblasts. Although histopathologically similar, the features of the lesions are not specific and also can be found in desmoplastic fibromas and simple odontogenic fibromas. The definitive diagnosis requires appropriate clinicopathologic correlation.

In situ hybridization analysis of human papillomavirus in orofacial lesions using a consensus biotinylated probe.

The effectiveness of the Viratype Omniprobe in situ human papillomavirus tissue hybridization kit (Digene Diagnostics) was evaluated for the detection of HPV DNA in common orofacial lesions. Seventy mucocutaneous lesions were hybridized with a biotinylated Omniprobe that was specific for HPV types 6, 11, 16, 18, 31, 33, 35, 42, 43, 44, 45, 51, 52, and 56. Eighteen (25.7%) of the specimens analyzed had intranuclear positive signals for HPV. Probing with HPV 6/11, 16/18, and 31/33/35 to delimit the HPV genotype yielded HPV DNA 6/11 in 16 (88.9%) of the Omniprobe-positive specimens. Only squamous papilloma and condyloma acuminatum were found to harbor HPV DNA. Sites most frequently infected were the labial and buccal mucosa (21.7%) and the floor of the mouth (17.4%). These results suggest that hybridization with the Omniprobe provides appropriate sensitivity and specificity for detecting HPV in some benign proliferations of the oral cavity. However, the detection of HPV in oral squamous cell carcinoma, lichen planus, and keratoacanthoma remains problematic until more sensitive and specific molecular techniques are used.

Mycosis fungoides: Initial diagnosis via palatal biopsy with discussion of diagnostic advantages of plastic embedding

The authors present an example of mycosis fungoides which was initially diagnosed from a palatal biopsy. The distinctive nuclear morphology of the tumor cells, with a discussion of their diagnostic importance, is presented. The advantages of plastic-embedded formalin-fixed tissue are delineated.