Oral squamous papillomas: detection of HPV DNA by in situ hybridization

Oral squamous papillomas were segregated from other papillary lesions on the basis of histopathologic features. Twenty representative papillomas were evaluated for the presence of papillomavirus genus-specific antigen with the use of an immunoperoxidase technique. These same tumors were analyzed for human papillomavirus (HPV) types 2, 4, 6, and 11 with biotinylated full-length double-stranded DNA probes by in situ hybridization. Only one case exhibited papillomavirus antigen reactivity. Alternatively, seven of twenty cases (35%) yielded positive results for HPV 6 or 11 DNA; one papilloma exhibited a dual infection with both HPV 2 and 6 when assayed under conditions of high-stringency hybridization. It is concluded that some oral squamous papillomas harbor HPV genotypes akin to those encountered in genital tract condylomas. Viral DNA can be detected in the absence of capsid antigen immunoreactivity, thereby obviating the use of antigen detection assays for determining the presence or absence of virus.     

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.     

Analysis of HPV 16 and 18 by in situ hybridization in oral papilloma of HIV+ patients

Human immunodeficiency virus (HIV) infection facilitates the development of other infections and lesions including oral papilloma, which has been associated with human papillomavirus (HPV). In analyzing the presence of HPV 16 and 18 by in situ hybridization in oral papillomas from five HIV+ male dental patients, HPV 16 and 18 were observed in 9 of 16 (52.2%) histopathologic specimens. All positive lesions occurred in heterosexual males admitting to oral sexual contact with a female partner (Pearson's correlation; p = 0.0088). These results suggest that oral sexual behavior may be a contributing factor in the presence of HPV 16 and 18 in oral papilloma.     

Oral inverted ductal papilloma associated with condyloma acuminata and HPV in an HIV+ patient

Oral inverted ductal papillomas are rare benign tumours of minor salivary glands. A case that appeared in a middle-aged HIV+ woman simultaneous to two condyloma acuminata on the lips is described. The presence of human papilloma virus (HPV) 11 DNA was demonstrated in all the samples using polymerase chain reaction. HPV could play an important role in the aetiology and pathogenesis of these lesions in this patient.     

Detection of human papillomavirus DNA in oral mucosal lesions using in situ DNA-hybridization applied on paraffin sections

The in situ DNA hybridization technique, carried out under stringent conditions, was used to detect human papillomavirus (HPV) DNA of types 6, 11, and 16 in paraffin sections of 32 surgically treated oral mucosal lesions. Expression of HPV structural proteins was analyzed by means of the immunoperoxidase (IP-PAP) method. A total of 10 (31.3%) of the 32 lesions proved to express HPV antigens, which were found in 4 of 7 squamous cell papillomas, in 2 of 2 classic condylomas, in 2 of 10 papillary hyperplasias, and in 2 of 3 leukoplakia lesions. Two of the squamous cell papillomas contained HPV 6 DNA, and 4 additional lesions were positive for HPV 11 DNA. In one of the condylomas, a double infection by HPV 6 and 11 was found, while the second was positive for HPV 11 alone. Both the HPV antigen-positive papillary hyperplasias contained HPV 6 DNA, as did the HPV antigen-positive leukoplakia lesions. Of the latter, one was infected by HPV 6 and 11. DNA of the "high-risk" HPV 16 was contained in two lesions: one lichen planus lesion and one of the two squamous cell carcinomas. The results confirm the previously reported evidence of HPV involvement in oral mucosal lesions. The implications of these findings are discussed in terms of the well-established premalignant character of oral leukoplakia and oral lichen planus, although far less commonly versus leukoplakia, with special emphasis on the discovery of the "high-risk" HPV 16 in the latter as well as in oral cancer.(ABSTRACT TRUNCATED AT 250 WORDS)     

In situ DNA hybridization analysis of oral papillomas, leukoplakias, and carcinomas for human papillomavirus.

Twenty-one papillomas, 23 ordinary benign keratoses, 13 smokeless tobacco keratoses, 10 verrucous hyperplasias, 10 verrucous carcinomas, 17 squamous cell carcinomas, 3 epithelial dysplasias, and 6 lichen planus lesions were evaluated for human papillomavirus (HPV) types 6/11, 16/18, and 31/33/35, with biotinylated double-stranded DNA probes by in situ hybridization. Sixty-two percent (13/21) of oral squamous papillomas were positive for HPV DNA. HPV DNA types 6 and 11 demonstrated the strongest reactivity. Of the 13 cases, 10 also showed some reactivity with HPV-16/18 and -31/33/35. None of the cases of keratoses, epithelial dysplasia, squamous cell carcinoma, verrucous hyperplasia, verrucous carcinoma, or lichen planus were positive for HPV DNA. This study confirms the consistent and frequent finding of HPV DNA in oral squamous cell papillomas and the inconsistency of being able to identify HPV DNA in keratotic, premalignant, or cancerous lesions of the oral mucous membranes.     

艾滋病毒感染患者口腔黏膜疣状肿块人类乳头状瘤病毒感染的分型研究

目的探讨艾滋病毒感染患者口腔戮膜疵状肿块人类乳头状瘤病毒(1-IPV)感染及感染类型。方法应用 HPV Ll区通用引物Gp5十//G p6+和1-IPV特型引物(HPV6/II,16,18,31,33),通过聚合酶链反应(PCR),对34例艾滋病毒感染患者口腔豁膜沈状肿块人类乳头状瘤病毒(HPV) DNA进行检测。结果艾滋病毒感染患者口腔豁膜优状肿块中,HPV感染率为88.2%;亚型HPV6/II感染率为47.06%, HPV16感染率为II.76%, 1U〕V 18感染率为 2.94 % , HPV31感染率为5.88%。结论艾滋病毒感染患者口腔庆状肿块和H PV感染关系密切,而且大多数和低危型HPV6/II感染有关,少数病例和高危型HPV16,18,31感染有关;同一病例可以感染两种以上HPV亚型。     

Papillary lesions of the oral cavity: relationship to human papillomaviruses

Human papillomaviruses are a group of genetically related organisms that infect stratified squamous epithelium. Unlike many other viruses that infect oral epithelium and induce lysis of the cells they penetrate, HPVs induce proliferative changes in these cells that result in both benign and malignant tumors. The common skin wart (verruca vulgaris) is induced by HPV 2 and 4. Genital warts (condylomas) and the common solitary oral papilloma are associated with HPV 6 and 11. Either HPV 13 or 32 causes focal epithelial hyperplasia. All of these wart-like lesions are benign growths of the stratified squamous lining of the oral cavity and lips and can be treated by surgical excision or laser ablation. HPV 16 and other less frequently encountered genotypes are associated with uterine cervix cancer in 95 percent to 98 percent of cases, and the evidence for a causal role is robust. There are emerging data that implicate HPV in certain subsets of oral cancer, particularly those that arise in the oropharynx/tonsillar region. Some instances of the various histologic subtypes subsumed under proliferative verrucous leukoplakia and verrucous carcinoma also harbor HPV.     

Oral mucosal changes in women with genital HPV infection

Sixty different types of human papillomavirus (HPV) are currently recognized. Of these, HPV types 1, 2, 4, 6, 7, 11, 13, 16, 18, 30, 32 and 57 have been identified in oral squamous cell lesions. The prevalence and incidence of clinical HPV infections of oral mucosa are incompletely established, and the figures on subclinical and latent infections are completely lacking. Similarly, no data exist on transmission of oral HPV infections. A long-term prospective follow-up study was started to assess the oral mucosal changes related to HPV infection in women with genital HPV infections. The aim was to elucidate whether genital HPV infections predispose the oral mucosa to this virus. This study reports the clinical, histologic and cytologic findings of oral mucosa as related to the genital status of 334 women prospectively followed-up in Kuopio University Central Hospital since 1981. At the time of examination, 5% presented with hand warts. Clinical wart in oral cavity was found in three patients (0.9%) only. Oral mucosa was clinically normal in 207 of 334 (62%) patients examined. Biopsies (n = 255) were taken from the buccal mucosa beneath the linea alba and above the sulcus in the region of the first molar, or from a lesion whenever present. Cytologic scrapings were taken from both sides of the buccal mucosa. Koilocytes were found in 0.9% of the cytologic scrapings, and in 9.4% of the biopsies. Altogether, four squamous cell papillomas and five flat condylomas were found in the biopsies. Morphologic changes suggestive for HPV were present in 25 biopsies. Hyperkeratosis proved to be a frequent finding (34%) in these biopsies.(ABSTRACT TRUNCATED AT 250 WORDS)     

Association between proliferative verrucous leukoplakia and infection with human papillomavirus type 16

Proliferative verrucous leukoplakia (PVL) is a recently described clinical entity characterized by multifocal oral lesions that frequently progress to oral cancer despite abstinence from tobacco use by most patients. To determine if this condition is associated with human papillomavirus (HPV), a polymerase chain reaction (PCR) for HPV DNA was performed on 9 lesions from 7 patients with PVL, histologically diagnosed with focal keratosis (1), papilloma (1), epithelial dysplasia (5) and squamous cell cancer (2). Eight (89%) were HPV positive, 7 for HPV 16. For comparison, we studied 55 non-PVL-associated oral specimens, including 24 oral squamous cell cancers. Of the cancers, 8 (33%) were HPV positive, 4 for HPV 16. These data suggest that HPV 16 infection may play an important role in the pathogenesis of PVL-associated oral dysplasia and possibly cancer, but is found in only a small proportion of the more common, non-PVL associated-oral lesions.     

Demonstration of human papillomavirus DNA in oral condyloma acuminatum

Condyloma acuminatum arising on oral mucous membranes exhibits distinct histopathological features that allow for differentiation from the more common squamous papilloma. These lesions are parakeratinized with cryptic invagination of cornified cells extending into an acanthotic spinous cell layer. Superficial spinous layer koilocytosis is a prominent feature and the condylomatous papillomas exhibit a tendency for sessile architecture. Among 62 instances, the average age was 39.7 years with a predilection for the 3rd and 4th decades. The male to female ration was 5.7:1 and the tongue, gingiva and lips were the favored sites. Whereas 25% of the evaluated cases demonstrated upper spinous layer papillomavirus common antigen immunoreactivity, DNA in situ hybridization under conditions of high stringency disclosed the presence of human papillomavirus Types 6, 11 or related genomes in 85% of the lesions. A single case was found to harbor human papillomavirus Type 2.     

Demonstration of human papillomavirus DNA in oral condyloma acuminatum

Condyloma acuminatum arising on oral mucous membranes exhibits distinct histopathologial features that allow for differentiation from the more common squamous papilloma. These lesions are parakeratinized with cryptic invagination of cornified cells extending into an acanthotic spinous cell layer. Superficial spinous layer koilocytosis is a prominent feature and the condylomatous papillomas exhibit a tendency for sessile architecture. Among 62 instances, the average age was 39.7 years with a predilection for the 3rd and 4th decades. The male to female ratio was 5.7:1 and the tongue, gingiva and lips were the favored sites. Whereas 25% of the evaluated cases demonstrated upper spinous layer papillomavirus common antigen immunoreactivity, DNA in situ hybridization under conditions of high stringency disclosed the presence of human papillomavirus Types 6, 11 or related genomes in 85% of the lesions. A single case was found to harbor human papillomavirus Type 2.     

Unusual HPV types in oral warts in association with HIV infection

Human papillomaviruses (HPV) are associated with certain oral soft tissue lesions, such as papillomas, warts, condylomata, and focal epithelial hyperplasia (FEH). HPV types 2, 6, 11, 16, and 18 have been identified in some of these oral lesions, while HPV 13 and 32 are associated with FEH. Little is known about the HPV types in oral warts of persons infected with human immunodeficiency virus (HIV). In this study, oral warts in 17 HIV-seropositive individuals were biopsied. Southern blot analyses were performed and the HPV types found were HPV 7 (7/17), 13 (1/17), 32 (1/17), and 18 (1/17). The presence of HPV type 7 is unusual in that it normally is found only in butcher's warts. There was no correlation between HPV type, histopathology, and clinical appearance of the lesions examined, except that the flat (FEH type) warts contained HPV types 13, 18 and 32 (1 of each). HIV infection appears to predispose individuals to oral infection with unusual HPV types.     

The human papilloma virus, the vaccines, and oral and oropharyngeal squamous cell carcinoma: what every dentist should know

High-risk human papilloma virus (HPV) strains 16 and 18 have been shown to cause cervical cancer as well as other benign and malignant disorders. Oral and oropharyngeal squamous cell carcinoma (OOSCC) has been linked to high-risk HPV strains. Recent developments in the field of immunology have resulted in a vaccine to treat patients with HPV against cervical cancer. The widespread use of the HPV vaccine should reduce the risk of cervical cancer and could decrease the risk of OOSCC as well. This article examines the virus as well as the vaccines and how they could be used. A possible reduction in oral and oropharyngeal cancers as a result of widespread vaccination is discussed.     

Unusual HPV types in oral warts in association with HIV infection

Human papillomaviruses (HPV) are associated with certain oral soft tissue lesiona, such as papillomas, warts, condylomata, and focal epithelial hyperplasia (FEH). HPV types 2, 6, 11, 16, and 18 have been identified in some of these oral lesions, while HPV 13 and 32 are associated with FEH. Little is known about the HPV types in oral warts of persons infected with human immunodeficiency virus (HIV). In this study, oral warts in 17 HIV-seropositive individuals were biopsied. Southern blot analyses were performed and the HPV types found were HPV 7 (7/17), 13 (1/17), 32 (1/17), and 18 (1/17). The presence of HPV type 7 is unusual in that it normally is found only in butcher's warrs. There was no correlation between HPV type, histopathology, and clinical appearance of the lesions examined, except that the flat (FEH type) warts contained HPV types 13, 18 and 32 (1 of each). HIV infection appears to predispose individuals to oral infection with unusual HPV types.     

Human papilloma virus: An etiological and prognostic factor for oral cancer?

The increasing prevalence of human papilloma virus (HPV)‐positive oral tumors can be considered an epidemic. Although the incidence of HPV cervical cancer is decreasing, the incidence of oral cavity and oropharyngeal cancers associated with HPV is increasing. The presence of certain HPV genotypes could be a predictor of future oral cancer lesions, although lesions associated with HPV could be less aggressive and exhibit a higher survival rate. In the present study, we review the most important biologic, clinic, epidemiologic, and prognostic factors associated with HPV infection and oral cancer.     

In situ detection of HPV DNA in oral mucosal lesions. A comparison of two hybridization kits

The purpose of this study was to compare the sensitivity of ViraType in situ hybridization kit (Life Technologies, Inc. [LT] and PathoGene (Enzo Diagnostics, Inc. [ED]) in situ hybridization kit for human papillomavirus (HPV) DNA detection in oral tissue. Forty benign oral lesions histologically suspicious for HPV infection were analyzed. Specimens were hybridized with DNA probes specific for HPV types 6/11, 16/18, and 31/33/35 [LT] and HPV types 6/11, 16/18, and 31/33/51 [ED]. Positive hybridization reactions were seen for HPV DNA type 6/11 only. Hybridization occurred significantly more often (p less than 0.01, McNemar Exact Test) in LT probed specimens (20/40) than ED assayed sections (12/40). HPV DNA sequences were found in 100% condyloma acuminata (13/13), 100% verruca vulgaris (4/4), and 13% squamous papilloma (3/23) using the LT system. The ED probes yielded positive signals in 77% condyloma acuminata (10/13), 25% verruca vulgaris (1/4), and 4.4% squamous papilloma (1/23). A more intense hybridization signal was exhibited using the LT system. The results indicate that the LT probes and detection reagents are more sensitive for detecting HPV DNA in oral mucosal specimens.     

Non radioactive in situ hybridization for detection of human papilloma virus DNA in squamous cell carcinoma of tongue.

Previous studies indicate that HPV type 16 and 18 (HPV) are associated with squamous cell carcinoma of the head and neck. In this investigation we evaluate in our hospital 253 patients with oral squamous cell carcinoma of the tongue not related to tobacco or alcohol with a tumor index of T2 NO MO between 1981 and 1991. From 12 patients we were able to obtain tissue. For detection of human papilloma virus, DNA sequences 6, 11, 16, 18, 31 and 33 in paraffin-embedded human tissue biopsies a non-radioactive in situ hybridization procedure was utilized. Approximately 60% of the carcinoma of the tongue are positive for episomal viral DNA 6, 11, 16 and 18. These results confirms that HPV infection may play a possible role in the multifactorial etiology of carcinogenesis of squamous cell carcinoma of the tongue and probably acting synergistically with other carcinogenesis.     

The clinical and histopathologic features of a series of 464 oral squamous cell papillomas

A clinical and histopathologic analysis of 464 oral squamous cell papillomas is presented. Data on age, sex, race, location, clinical appearance, duration, recurrence, and clinical diagnosis are reviewed. One hundred seventy-six of the 464 specimens were examined for hyperkeratosis, character and amount of inflammatory infiltrate, and evidence of cellular atypia. The trends seen in this study support claims made by previous authors regarding incidence and inflammatory involvement. The data support a slightly higher occurrence rate in males than in females and in white as opposed to black patients. Papillomas were most abundant on the palatal complex, dorsum and lateral tongue borders, and lower lips, respectively. Confusion of papilloma for fibroma in the clinical diagnosis was less common than expected. Recurrence rate and incidence of multiple papillomas were low. Histologic study revealed a tendency for hyperkeratotic lesions to arise from nonkeratinized oral sites. Cellular atypia was found, but it is still unclear whether these changes are preneoplastic or due to an increased growth rate.     

Peroxidase-antiperoxidase evaluation of human oral squamous cell papillomas

In human beings, the viral origin of condylomatous lesions of the mouth and cervix, multiple papillomas, and verruca vulgaris of the larynx has been established. The viral origin of papillomatosis in rabbits and dogs has also been documented. The literature, however, shows no conclusive evidence of a viral origin of human oral squamous cell papillomas (SCP). The purpose of this study was to use the peroxidase-antiperoxidase (PAP) staining technique to determine whether human papillomavirus (HPV) antigens exist in serial step sections of human oral SCP. Fifty human oral SCPs were randomly selected from the department files, and tissue sections were subjected to an indirect immunoperoxidase-PAP technique. Evidence of HPV-Type I virus antigens was found in 2 of 50 papillomas studied (2 of 194 tissue sections). This suggests that all oral SCPs are not of viral antigen.