Human Papillomavirus in the Oral Cavity

Abstract

Human papillomavirus (HPV) cannot be efficiently propagated in tissue cultures or animal models. However, molecular biological technology has made it possible to clone viral genomes, which can then be compared and also used as reagents in clinical and epidemiological studies.Today HPV infections are recognized as being responsible for inducing cancers worldwide and it is expected that HPV-based technologies will provide the tools to prevent and treat HPV-induced cancers. In this review, we focus on the association between oral lesions and HPV infection and the natural history of HPV infection of the oral cavity. We also evaluate the HPV detection methods in this important and fundamental matter for the HPV studies. We then discuss the potential targeted molecular therapies and prevention of a variety of HPVinduced diseases of the oral cavity, including oral cancers. Key words: HPV, human papillomavirus, oral cavityCorrespondence : Minoru Takagi, Molecular Pathology, Oral Restitution, Oral Health Science, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113- 8549, JapanPhone: +81-3-5803-5451, Fax: +81-3-5803-0188 IntroductionHuman papillomavirus (HPV) is a small, nonenveloped and double stranded circular DNA virus, about 8,000 bp in length, with a well-known physical structure and gene organization (1). HPV belongs in the subfamily papillomavirus (PV) of the papovavirus family, which are widely distributed in nature and infect many higher vertebrates including cattle, rabbits and dogs (1). It is thought that the viruses may have co-evolved with their hosts (2). They are highly species-specific species, having one or more of its own PVs, and viruses of one species do not infect other species (1).HPV is classified into more than 100 types, including 84 clones and others detected by PCR (3). To be recognized as a distinct HPV genome, the full genome should be cloned and the sequence of the L1 gene should be no more than 90% similar to previously assigned and referenced HPVs (4). HPVs naturally fall into two groups: mucosal HPVs and cutaneous HPVs according to the anatomic site of infection and/or phylogenetic analysis (5). Some HPV infections can lead to malignant lesions depending on HPV genotypes and infection persistence. HPV is also broadly categorized into low, intermediate and highrisk types in accordance with their potential to induce or their association with malignant lesions (6). In oral lesions 24 genotypes have been identified 2,3,4,6,7,10,11,13,16,18,30,31,32,33,35,45,52,55,57,59,69,72 and 73) (7-27) ( Table 1).The HPV genome is comprised of early (E) genes that function primarily in episomal replication and late (L) genes that encode the viral capsid proteins. HPV 16 genome map is shown in Fig. 1. The L1 and L2 genes code for proteins that make up the viral major and minor capsid. The capsid encloses the viral genome and mediates viral entry into susceptible cells (28). Much of the immune response to infection is directed at the capsid protein (29). Based on experi...

Prevalência do papilomavírus humano (HPV) na cavidade oral e na orofaringe

“…Among the factors that generate controversy about HPV prevalence in the normal oral mucosa seen on Table 1, we can stress the large variation in HPV detection rates, from 0% to 100% despite the use of more sensitive methods -such as PCR; another factor is the relationship between results and sample sizes, which varied in 3 samples, with 100% positiveness for HPV in the Tominaga et al 64 study from 1996, reaching up to 212 samples with 15% of HPV detection in the Kellokoski et al 65 study from 1992, thus showing a great difference between the results, which is probably due to a failure in the HPV detection methods or in harvesting the material or, even, because we do not know the exact HPV infection pathway in the normal oral mucosa 32,13,16 .…”

“…In the normal oral mucosa we have seen a great variation in HPV rates detected, from 22% to 60% 17 ; from 0% all the way to 81.1% in studies using different methods, and with a limited number of individuals, and this seems to depend on the population studied and the choice of method 16,21 . It has been suggested that HPV prevalence in the normal mucosa includes subclinical and/or latent infections, and that the infection with a low number of virus copies is common in the oral cavity 8 .…”

“…Notwithstanding, the assessment of different methods used to detect HPV16 is important and fundamental in order to establish the etiological role of HPV in oral lesions. Table 1 shows HPV 16 prevalence in the normal oral mucosa in 16 results from 14 authors, by the SB, ISH and PCR detection methods, making up 56% of all the results, and this seems to depend on the population examined and the choice of method used to detect HPV 21,16 .…”

“…Each method is limited by its sensitivity, specificity, its practice, cost and its commercial availability. It is important and fundamental to assess the efficacy of different HPV detection techniques, in order to establish HPV etiology in oral lesions 10,16 .…”

Análise comparativa da proliferação celular entre carcinomas de células escamosas orais HPV-positivos e HPV-negativos

“…As oncoproteínas virais E6 e E7 são as mais importantes nesse processo, pois são capazes de ligarem-se às proteínas p53 e pRb, respectivamente, e interferirem em suas funções normais (23,26) . Além disso, a proteína E6 também apresenta importante papel na ativação da telomerase, contribuindo para o processo de imortalização dos ceratinócitos (11) .…”