Human papillomavirus (HPV) infections and their associations with oral disease

More than 65 distinct types of human papillomavirus (HPV) have been identified to date. Several of the HPV types have been proposed as etiologic agents of squamous cell carcinoma. In the oral cavity, HPVs have been found associated with several benign squamous cell proliferations. Evidence from histology and DNA hybridization studies suggests that HPV is also involved in oral carcinogenesis. It is apparent, however, that substantial amount of confusion exists in the diagnosis of oral HPV infections. The keratotic, papillary lesions in the oral cavity are usually small and easily overlooked. The gross appearance of these viral lesions is not distinct enough to be readily diagnosed by the clinicians. Degenerative changes found on oral mucosa frequently simulate koilocytosis. Thus, caution should be exercised to avoid overdiagnosis of HPV infection in the oral cavity. The present review summarizes the current evidence available on HPV infections in general and on oral HPV infections in particular. The diagnostic techniques available as well as the problems encountered in the distinction of these lesions are also discussed in short.     

Dot blot hybridization in detection of human papillomavirus (HPV) infections in the oral cavity of women with genital HPV infections

The presence of human papillomavirus (HPV) types 2, 6, 7, 11, 13 and 16 DNA in cytologic scrapings of oral mucosa was studied in 309 women with genital HPV infections. The objective was to test the usefulness of oral mucosal scrapings (3 sequential swabs) in HPV DNA detection by dot blot hybridization. Based on hybridization with the 32P-labelled Alu-repeat probe, most samples contained more than 10(5) cells, which is an adequate number of cells for dot blot hybridization. Hybridization with 32P-labelled HPV DNA probes showed that 3.8% of the 309 women had an oral HPV infection. Of these, only 2 had clinical lesions indicative of HPV. All other oral HPV positive subjects had clinically healthy mucosa. HPV 6 was the most common (3.1%) type, followed by HPV 11 and 16 (1.1%). In 3 cases the genital mucosa harboured the same HPV type as found in the oral cavity. The results indicate that oral mucosal scraping results in adequate number of cells for dot blot hybridization with HPV DNA. Although the method is likely to result in an underestimation of latent and subclinical HPV infections, it is useful for studying the clinical HPV infections as well as other viral infections known to be present in exfoliated cells.     

Two different human papillomavirus (HPV) types associated with oral mucosal lesions in an HIV-seropositive man

Different types of Human papillomaviruses (HPV) are associated with a variety of oral lesions. So far, HPV types 1, 2, 4, 6, 7, 11, 13, 16, 18, 32 and 57 have been identified in oral lesions. Immunosuppression predisposes oral mucosa to clinical manifestation of different virus infections including HPV. We describe here a 30-year-old HIV-positive and immunosuppressed man, who had suffered from oral lesions for a few months. On clinical examination, a nodular elevation was detected on the lower lip, and white keratotic areas were present on buccal mucosa bilaterally. A biopsy from the lip revealed the presence of acanthosis with a prominent granular cell layer as well as hyperparakeratosis. A biopsy from the buccal lesion showed a comparatively much flatter lesion with merely basal cell hyperplasia associated with hyperparakeratosis. Koilocytosis was a characteristic feature in both biopsies. In Southern blot hybridization, both lesions hybridized with a probe cocktail comprising HPV 6, 11, 16, 18, 31 and 33 DNA under low stringency. Under high stringency, the lip lesion proved to contain HPV 7 DNA, which also confirmed by in situ hybridization. The buccal lesion was weakly positive by Southern blot with HPV 11 and 13 probes hybridized under stringent conditions, but the restriction patterns with Pst I and Bam HI did not fit with those of any of the 57 HPV types known so far. In situ hybridizations with HPV 11 and HPV 13 probes were negative. Cloning of this 'new' HPV type is currently under way.     

Human papillomavirus (HPV) types 2 and 57 in oral verrucae demonstrated by in situ hybridization

Twenty-one cases of verrucae vulgaris (oral warts) were investigated for human papillomavirus (HPV)-group specific antigen by immunocytochemistry and for HPV types 1, 2, 4, 6, 11, 16, 18 and 57 by DNA in situ hybridization with biotinylated probes. Twelve (57%) cases demonstrated the presence of HPV-group specific antigen. Fifteen (71%) cases showed the presence of HPV DNA, 13 of which (87%) demonstrated both HPV types 2 and 57 in the same cells and 2 of which (13%) demonstrated only HPV 2. Six cases were negative for HPV 2 and 57 and all 21 cases (100%) were negative for HPV types 1, 4, 6, 11, 16 and 18. Results indicate the association of a new and as yet unidentified HPV type, closely related to HPV 2 and 57, with oral warts. The identification of both cutaneous type HPV 2 and another type closely related to HPV 2 and 57 in oral verrucae on keratinized and non-keratinized mucosal surfaces indicates the possibility of a latent infection; three patients had a history of warts on their hands, suggesting autoinoculation. This study indicated that future investigations of oral warts, based on a correlation of clinical and histological features with HPV types by DNA in situ hybridization, are called for.     

Association of marijuana use with oral HPV infection and periodontitis among Hispanic adults: Implications for oral cancer prevention

1 Background

Despite limited data, research suggests that marijuana use is associated with oral HPV infection and periodontitis, two potential oropharyngeal cancer risk factors. We assessed these associations in a Hispanic adult population in Puerto Rico.

2 Methods

A cross‐sectional study of 735 adults assessed marijuana use, determined through an audio computer‐assisted self‐interview, and periodontitis and self‐collection of oral HPV samples following the National Health and Nutrition Examination Survey methodology. The Centers of Disease Control and Prevention/American Academy of Periodontology definition was used for periodontitis. HPV typing was performed using polymerase chain reaction with modified L1 consensus primers (MY09/MY11).

3 Results

26.5% of adults reported lifetime use of marijuana, 2.7% were frequent users (lifetime use ≥ 26 times, past year use ≥ 6 times, and past 30‐day use ≥2 times), 5.7% had oral HPV infection, and 20.1% had severe periodontitis. The multivariate logistic regression analysis showed that frequent marijuana users were more likely to have severe periodontitis (OR = (2.93, 95%: 1.08–7.96)) than never/once lifetime users after adjusting for age, sex, healthcare coverage, smoking, binge drinking, number of oral sex partners, and oral HPV infection. However, frequent marijuana use was not associated with oral HPV infection.

4 Conclusion

Marijuana use was associated with periodontitis, but not with oral HPV infection. Further evaluation of the role of marijuana use in oral HPV infection and periodontitis may inform novel preventive public health strategies, as marijuana users could be at increased risk of oral cancer.     

口腔粘膜病损HPV的检测

应用ＰＣＲ技术检测口腔粘膜病损中ＨＰＶ的感染情况。病损包括白斑、扁平苔藓、慢性盘状红斑狼疮、日光性唇炎、鳞癌及鳞癌术后上皮高度增生共３４例。结果表明在口腔癌与白斑中斑可存在ＨＰＶ的感染，ＨＰＶ可能是口腔癌的致病因子之一。     

Local immunoreactivity and human papillomavius (HPV) in oral precancer and cancer lesions

Abstract – A retrospective longitudinal study was performed on 20 patients with oral leukoplakia, 10 of which developed an oral squarnous cell carcinoma, to assess whether any alterations in the local immunologic reactivity could be found of value in predicting the subsequent behavior of the lesions. During the major period of follow-up, the relative frequency of in situ IgA-producing plasma cells was significantly higher in biopsies from patients subsequently developing cancer than in patients showing no cancer development. Preceding the malignant transformation by 12 to 15 months, however, a remarkable shift from IgA to IgG plasma cell predominance was noticed in the biopsies of the cancer series, not detectable in the non-cancer group. HPV group specific capsid antigens were found in seven cases of the cancer series and in six of the non-cancer group. The possible diagnostic implications of these results are discussed.     

Evaluation of oral and laryngeal specimens for human papillomavirus (HPV) DNA by dot blot hybridization

Human papillomavirus (HPV) is an infectious agent which is increasingly associated with mucosal cancers, in particular, cancer of the cervix. The present investigation was undertaken in an attempt to determine whether the Virapap human papillomavirus (HPV) DNA detection kit, originally designed for identification of HPV in exfoliated cervical cells could be employed in detection of HPV in biopsies of oral and laryngeal tissue samples, specifically oral squamous cell carcinomas, epithelial dysplasias, smokeless tobacco keratoses, and laryngeal papillomatosis. The ViraPap HPV DNA detection assay was found to be useful for HPV DNA identification in tissue samples from oral and laryngeal specimens.     

Human papillomavirus DMA in oral squamous cell carcinomas and normal mucosa

Human papillomavirus (HPV) infections in oral carcinomas and normal oral mucosa were studied by consensus primer screening and typing for HPV types 6/11,16 and 18 DNA. After polymerase chain reaction (PCR) the DNA species of interest were identified by Southern blot hybridization with digoxigenin-labeled oligonucleotide probes. Frozen tissue and scrapings were equally suitable for HPV testing and yielded high HPV detection rates in carcinomas. By comparison, HPV analysis of paraffin-embedded material was much less efficient. HPV were demonstrated in 61.5% (16/26) of oral squamous cell carcinomas, high risk HPV 16 and 18 being the preferential types. The frequency of HPV detection in non-neoplastic mucosa of tumor patients decreased clearly with increasing distance from the tumor (range 26.9–3.8%) suggesting focal HPV infections. In contrast, normal buccal mucosa of a group of healthy volunteers contained HPV DNA only in 1%(1/97).     

National prevalence of oral HPV infection and related risk factors in the U.S. adult population

This article reviews the rapidly growing evidence that oral human papilloma viruses (HPV) infection contributes to the risk of oral squamous cell carcinoma. It also reports the first nationally representative estimates of oral HPV prevalence in the United States adult population. An estimated 7.3% (95% CI: 6.0, 8.9) of the U.S. population had one or more oral HPV types detected in oral rinse; 3.1% (95%CI: 2.4, 3.9) of the U.S. population had one or more oncogenic HPV types. A substantial excess risk of HPV infection in men is not explained by education, smoking, age of sexual debut, or number of lifetime sex partners. Based on the published finding from a case-control study, where there was an odds ratio of 2.6 (95% CI: 1.5, 4.2) for the association of head and neck cancer oncogenic oral HPV infection, the estimated population attributable risk for head and neck cancer in the U.S. population was 4.7%. In other words, there would be a 4.7% reduction in incidence rate of head and neck cancer in the United States if oncogenic HPV infection could be prevented. The results also provide population data that help evaluate the likely public health benefits of prophylactic vaccination against oral HPV acquisition.     

Comparative study of HPV prevalence in Japanese and North-east Chinese oral carcinoma

BACKGROUND: Human papillomavirus (HPV) plays a role in the development of oral carcinoma. However, the reported prevalence of HPV in oral carcinoma has varied widely. METHODS: The prevalence of HPV 16, 18 and 33 was investigated in Japanese and North-east Chinese oral squamous cell carcinomas (OSCCs) with polymerase chain reaction (PCR). The expression of p53 protein was examined immunohistochemically. RESULTS: HPV 16 and 18 were detected in 7 (23.3%) and 10 (33.3%) of 30 Japanese and 11 (36.7%) and 5 (16.7%) of 30 Chinese samples, respectively. HPV 16 and 18 coinfection was detected in 3/30 Japanese and 2/30 Chinese samples. HPV 33 was not detected. There was no significant correlation between HPV 16 and 18 and the sites, gender, age and histological grade. The prevalence of both HPV 16 and 18 was similar and higher in the Japanese and North-east Chinese samples (46.7% each). HPV 16 or/and 18 infection or/and p53 overexpression were in 22 (73.3%) of 30 Japanese samples and 24 (80.0%) of 30 North-east Chinese samples, respectively. CONCLUSIONS: HPV 16/18 infection or/and p53 overexpression may play an important role in developing some OSCCs. and the presence of HPV sequences and mutant p53 are not necessarily mutually exclusive.     

Evaluation of argyrophilic nucleolar organizer regions (AgNORs) in oral carcinomas in relation to human papillomavirus infection and cytokinetics

The numbers of argyrophilic nucleolar organizer regions (AgNORs) were quantified in oral carcinomas ( n = 39) with or without human papillomavirus (HPV) infection. The AgNOR counts of the HPV-positive samples (7.15±2.13) were not significantly ( P = 0.09) higher than those of the HPV-negative ones (6.16±1.89). Furthermore, the lesions infected with multiple HPV types had greater counts than those with HPV type 16/18 infection alone. Significant differences were observed between the mean counts of the poorly (10.50±0.54), moderately (7.31±1.07) and well- (5.12±0.85) differentiated carcinomas. The mean AgNOR numbers in the oral carcinomas at TNM stages III/IV were found to be significantly ( P < 0.01) higher than the numbers in corresponding stage II lesions. Cytokinetics of the lesions assessed by the bromodeoxyuridine (Brdu) labelling index (LI%) showed a linear correlation (r=0.91: P < 0.0001) with their respective mean AgNOR counts.     

正常口腔黏膜和口腔鳞癌中人乳头瘤病毒感染率的研究进展

黏膜高危型HPV-16、HPV-18感染是宫颈癌的主要致病因素,且与口腔鳞癌的发生密切相关,但目前对口腔鳞癌中HPV的感染率和亚型的分布尚不十分清楚。作者系统查阅了目前已经发表的有关HPV在正常口腔黏膜或口腔鳞癌中感染率和亚型分布的文献资料,对正常口腔黏膜、口腔鳞癌中人乳头瘤病毒的感染率的研究进展进行了综述。     

Matrix metalloproteinases (MMPs) in oral diseases

Matrix metalloproteinases (MMPs) are a group of enzymes that in concert are responsible for the degradation of most extracellular matrix proteins during organogenesis, growth and normal tissue turnover. The expression and activity of MMPs in adult tissues is normally quite low, but increases significantly in various pathological conditions that may lead into unwanted tissue destruction, such as inflammatory diseases, tumour growth and metastasis. MMPs have a marked role also in tissue destructive oral diseases. The role of collagenases, especially MMP-8, in periodontitis and peri-implantitis is the best-known example of the unwanted tissue destruction related to increased presence and activity of MMPs at the site of disease, but evidence has been brought forward to indicate that MMPs may be involved also in other oral diseases, such as dental caries and oral cancer. This brief review describes some of the history, the current status and the future aspects of the work mainly of our research groups looking at the presence and activity of various MMPs in different oral diseases, as well as some of the MMP-related aspects that may facilitate the development of new means of diagnosis and treatment of oral diseases.     

湖北地区HIV阳性人群口腔内HPV感染状况研究

目的：对HIV感染者口腔黏膜乳头状瘤病毒（HPV）感染进行研究,并对比其中女性宫颈的感染状况,了解湖北地区HIV感染者口腔内HPV感染的流行和分布,证实HPV与HIV之间及相关疾病的相互关系。方法：收集40例自愿接受检查的HIV感染者的一般情况,检测其CD4＋T细胞计数,并对受检者中的女性进行宫颈检测,使用PCR方法检测口腔及宫颈处HPV亚型,采用SPSS 17．0软件进行统计分析。结果：有1例（2．5％）患者检测出口腔HPV52型,10例女性患者（38．5％）在宫颈黏膜样本中检测出HPV感染,且有2例同时检测出2种以上HPV基因型。结论：HIV感染者口腔内HPV感染率远低于宫颈黏膜HPV感染率,两区域间HPV感染状况没有明显联系。     

High risk human papillomavirus in oral squamous carcinoma: evidence of risk factors in a Venezuelan rural population. Preliminary report

In a search for the presence of human papillomavirus (HPV) and some etiologic cofactors in oral squamous cell carcinoma (OSCC), 50 women diagnosed as OSCC were analyzed by a multiplex polymerase chain reaction (PCR) assay specific for HPV types 6, 11, 16, and 18. This study revealed that 60% (30/50) of the OSCC patients were positive for HPV-DNA sequences. This group was analyzed according to smoking, alcohol consumption, number of pregnancies, poor oral health and low social economic status. The current results indicate an increased incidence of HPV malignant types in the oral cavity in women with OSCC. Also, they support a multifactorial model of oral cancer causation.     

High prevalence of oral human papillomavirus infection in Fanconi's anemia patients

Oral Diseases 17 , 572–576 Background: Fanconi’s anemia (FA) is a rare recessive genetic disorder characterized by bone marrow failure, developmental and congenital abnormalities, which frequently evolves to aplastic anemia and neoplasias, primarily acute leukemia and head‐neck carcinomas. Risk of malignancies increases after hematopoietic stem cell transplantation (HSCT), and the role of human papillomavirus (HPV) in FA carcinogenesis have been proposed. Objective: To investigate prevalence of oral HPV in FA patients without oral malignant lesions. Materials and methods: After oral examination, 76 subjects without detectable oral malignant lesions were included and classified in four groups: 20 FA submitted to HSCT (I), 22 FA not submitted to HSCT (II), 18 severe aplastic anemia (SAA) submitted to HSCT (III) and 16 healthy subjects (IV). Liquid‐based cytology sampling, HPV screening by polymerase chain reaction and genotyping by reverse hybridization were performed. Results: The HPV detection rates were: group I 35%, group II 27.3%, group III 38% and group IV 6.25%. Prevalence of high risk HPV types, mainly HPV16, was detected. Compared with control group, suggestions for increased likelihood of being HPV infected in SAA (OR = 9.55, 95% CI: 1.01–125.41) and FA patients submitted to HSCT (OR = 8.08, 0.83–72.29) emerged. Conclusion: Patients without oral malignant lesions submitted to HSCT, have high prevalence of oral HPV. HPV screening and close follow up should be considered in these patients.     

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.