Hiperplasia epitelial focal: relato de caso clínico / Focal epithelial hyperplasia: case report

Introdução: a hiperplasia epitelial focal (HEF) ou doença de Heck, caracteriza-se por ser uma lesão benigna rara da mucosa bucal. Geralmente, está associada a proliferação do epitélio pavimentoso atribuída principalmente ao papiloma vírus humano (HPV) dos subtipos 13 e 32. Objetivo: relatar o caso de um paciente, com suspeita diagnóstica de HEF, descrever suas manifestações clínicas bucais e histopatológicas. Metodologia: homem, 38 anos, melanoderma, compareceu no Serviço Universitário com queixa de ardência em mucosa bucal. Ao exame clínico, apresentava múltiplas lesões papulares, firmes à palpação, de coloração rósea, com pápulas aglomeradas ou isoladas, localizadas em rebordo alveolares, gengiva inserida e livre da arcada superior e inferior, mucosas jugais e labiais, compatíveis com lesões causadas por HPV. Realizou-se biópsia incisional das lesões bucais, o laudo histopatológico descreveu o fragmento de mucosa bucal que estava revestida por epitélio pavimentoso estratificado paraceratinizado com acantose proeminente, projeções focais confluentes para o tecido conjuntivo, confirmando a suspeita diagnóstica clínica. Conclusão: a HEF é uma patologia rara, benigna da mucosa, indolor e que pode se resolver espontaneamente. Portanto, é necessário o diagnóstico adequado através da biopsia e laudo histopatológico.

Introduction: focal epithelial hyperplasia (FEH) or Heck's disease is characterized as a rare benign lesion of the oral mucosa. It is usually associated with proliferation of the squamous epithelium, mainly attributed to human papillomavirus (HPV) subtypes 13 and 32. Objective: to report the case of a patient with a diagnostic suspicion of HEF, to describe its oral clinical and histopathological manifestations. Methodology: hale, 38 years old, black, attended the University Service with a complaint of burning in the oral mucosa. On clinical examination, she presented multiple papular lesions, firm to palpation, pink in color, with agglomerated or isolated papules, located in the alveolar ridge, inserted gingiva free from the upper and lower arch, jugal and labial mucosa, compatible with lesions caused by HPV. An incisional biopsy of the oral lesions was performed, the histopathological report described the fragment of oral mucosa that was lined with parakeratinized stratified squamous epithelium with prominent acanthosis, focal projections confluent to the connective tissue, confirming the clinical diagnostic suspicion. Conclusion: FEH is a rare, benign mucosal pathology, painless and can resolve spontaneously. Therefore, proper diagnosis through biopsy and histopathological report is necessary.

Genomic characterization of human papillomavirus type 13, associated to multifocal epithelial hyperplasia, in a Mayan community.

Human papillomavirus type 13 (HPV13) is a low-risk HPV type associated with Multifocal Epithelial Hyperplasia (MEH). It is considered a rare pathology of oral mucosa, more prevalent in certain ethnical groups, such as the Maya from Yucatan in Mexico. As for 2020 only two complete genomes of HPV13 are publicly available in Genbank database (one from Turkey one from the Amazonian). We aimed to obtain the complete genome sequence of HPV13 associated to MEH, obtained from a community in the Mayan area from Mexico. A bank of oral swabs from children with MEH were used. To enrich the sample, a Rolling Cycle Amplification (RCA) method was performed followed by overlapping end-point PCR of 500 bp fragments, Sanger sequencing and assembly. Eight open reading frames (ORFs) were annotated (E1, E2, E4, E5, E6, E7, L1 and L2 genes). When compared with the other two previously reported genomes the identity at nucleotide level is high 98.9% and 99.6%, respectively. The phylogenetic tree shows that Yucatan HPV13 is more closely related to HPV13 obtained from the Amazonian. Most changes identified at amino acid level are substitutions derived from nucleotide variations or SNPs in coding regions. Amino-acid changes were observed in E2 and E1 proteins (n ≥ 8), and in L1, L2, E6 and E5 proteins (n ≤ 5). E7 protein from Yucatan has 100% identity with the reported from Amazonian and differs (94.1% identity) with the one from Turkey due to 3 substitutions and three missing amino acids. In conclusion, the genome from HPV13 (7831 bp, 49 nt missing) associated to MEH in the Mayan area from Yucatan was obtained from stored swabs; this is the first effort in Mexico, the second in Latin America, and the third of the world. More research that contributes to the knowledge of the determinants underlying this neglected pathology are urged.

Prevalence of Oral Human Papillomavirus Infection Among Australian Indigenous Adults.

Importance: Human papillomavirus (HPV) infection is associated with oropharyngeal squamous cell carcinoma. International estimates suggest overall oral HPV prevalence is 7.5%, with prevalence of oral HPV types 16 and 18 being 1.6%; prior Australian estimates suggest oral HPV prevalence is 2.3%, with HPV-16 and HPV-18 being 1.3%. Objectives: To estimate the prevalence of oral HPV infection among Indigenous Australians and to report the prevalence of factors associated with high-risk HPV types (ie, HPV-16 and HPV-18) and HPV types linked with Heck disease (ie, HPV-13 and HPV-32). Design, Setting, and Participants: This cross-sectional study analyzed HPV screening results from saliva samples collected from 1011 Indigenous Australians between February 2018 and January 2019. Data were analyzed from May 2018 to May 2019. Recruitment occurred through Aboriginal Community Controlled Health Organisations in South Australia. Eligibility included identifying as Indigenous, residing in South Australia, and being aged 18 years or older. Main Outcomes and Measures: Saliva samples were collected, with microbial DNA for genotyping extracted. Sociodemographic parameters, health-related behaviors, and sexual history data were collected. Analyses were stratified by sex as well as by HPV types 13 and 32 (Heck disease) and 16 and 18 (high risk of oropharyngeal squamous cell carcinoma). Multivariable analyses were conducted to obtain adjusted odds ratios (ORs). Results: Data were obtained for 910 participants (median [interquartile range] age, 37 [27-51] years); 595 participants (65%) were female and 572 (63%) resided in nonmetropolitan locations. In all, 321 saliva samples (35.3%; 95% CI, 32.2%-38.4%) were positive for oral HPV (106 [33.7%] men; 215 [36.1%] women). The highest prevalence was found for HPV types 13 and 32 (207 [22.7%] total; 60 [19.0%] men; 147 [24.7%] women) followed by HPV types 16 and 18 (30 [3.3%] total; 9 [2.9%] men; 21 [3.5%] women). After multivariable analysis, risk factors associated with HPV types 13 and 32 included nonmetropolitan residential status (OR, 2.06; 95% CI, 1.10-3.88) and not having had a tonsillectomy (OR, 2.74; 95% CI, 1.05-7.16). Among women, having obtained a high school education or less was associated with lower odds of HPV-16 and HPV-18 infection (OR, 0.16; 95% CI, 0.03-0.97). Conclusions and Relevance: Prevalence of oral HPV infection in a large sample of Indigenous Australians was high, with one-third testing positive. The most prevalent HPV types were those associated with Heck disease. The prevalence of HPV types associated with oropharyngeal squamous cell carcinoma exceeded both Australian and international population-level estimates.

Oral human papilloma virus infection: an overview of clinical-laboratory diagnosis and treatment.

OBJECTIVE: The aim of this review is to describe the "hot points" of current clinical governance for oral HPV comprising the use of new diagnostic molecular procedures, namely, Pyrosequencing and Next Generation Sequencing. MATERIALS AND METHODS: The data on oral HPV was collected through two levels of research. First for all, we used the canonical medical search engines, PubMed, and Medline, followed by the study of current commercial tools for HPV diagnosis, particularly within commercial companies involved in the molecular procedures for HPV detecting and genotyping. RESULTS: Different medical procedures are now described and used throughout the world in HPV diagnosis and treatment. However, the laboratory methods are often validated and used for genital infections, and, in these cases, data are missing in the literature as regards the clinical approach for oral lesions. CONCLUSIONS: Dental care units are often the front line for a clinical evaluation of a possible HPV lesion in the oral cavity, which means that correct clinical governance could avoid a viral neoplastic progression of this disease with great advantages for the patient. In this case, the problem is due to the difficulty in lesion recognition but also and more especially the absence of correct laboratory diagnosis and subsequent treatment in the clinical course.

Use of trichloroacetic acid for management of oral lesions caused by human papillomavirus.

The human papillomavirus (HPV) has an affinity for squamous cells of stratified keratinized epithelium, thus affecting the lower genital, nasal, and oral tracts. In the oral cavity, HPV is associated with pathoses such as the verruca vulgaris (common wart), squamous cell papilloma, condyloma acuminatum (venereal wart), and focal epithelial hyperplasia (Heck disease). Among the treatments available for these lesions are cryotherapy, electrosurgery, surgical removal, laser therapy, and trichloroacetic acid (TCA). The objective of this research was to determine the behavior of HPV-associated oral pathoses treated with TCA. A prospective cohort study was performed in 20 patients who attended a dental consultation at 2 universities in Cartagena, Colombia. Among the patients, 65% were diagnosed as having focal epithelial hyperplasia, 20% as having verrucae vulgares, and 15% as having condylomata acuminata. Application of TCA to HPV-associated oral lesions proved to be a useful nonsurgical alternative treatment, as the resolution of the lesions was achieved atraumatically in a span of 45 days with 3 applications of 30-60 seconds each.

Human papillomavirus detection in histologic samples of multifocal epithelial hyperplasia: a novel demographic presentation.

OBJECTIVE: Human papillomavirus (HPV) typing of oral lesions microscopically consistent with multifocal epithelial hyperplasia (MEH) was performed to identify potential novel clinical presentations. STUDY DESIGN: MEH (N = 22 lesions, 17 patients) and squamous papilloma control samples (N = 9 lesions, 9 patients) were compared by using polymerase chain reaction-based HPV genotyping. Student's t tests were used to compare continuous characteristics. RESULTS: Of the study cases, 86.4% of MEH and only 11% of controls were positive for HPV (P = .0002). In MEH lesions, 45.5% contained HPV32, 36.4% HPV6, and 4.5% HPV40. MEH lesions were mostly multifocal (50%) and occurred in HIV-negative patients (81.3%). They predominated on the labial/buccal mucosa (63.3%), and there were significant differences between groups by anatomic site (P < .0001). HPV32, but not HPV6, was detected in known HIV-positive patients. CONCLUSIONS: A novel clinical presentation of MEH associated with HPV32 in HIV-negative, middle-aged to older adults is reported here. One case with HPV40 is the first to be reported. Future detection protocols should include HPV32, as it may be currently overlooked.

Focal epithelial hyperplasia by human papillomavirus (HPV)-32 misdiagnosed as HPV-16 and treated with combination of retinoids, imiquimod and quadrivalent HPV vaccine.

Focal epithelial hyperplasia (FEH) or Heck's disease is a rare, benign and asymptomatic mucosal proliferation associated with human papillomavirus (HPV) infection, mainly with genotypes 13 and 32. We report a florid case of FEH in an 11-year-old Haitian girl with systemic lupus erythematosus receiving immunosuppressive therapy. Cryotherapy was previously performed on numerous occasions with no results. We decided to prescribe a non-invasive and more comfortable treatment. A combination of topical retinoid and imiquimod cream was well tolerated and led to an important improvement. The evidence of infection by HPV-16 detected by polymerase chain reaction (PCR) technique, prompted us to prescribe the quadrivalent HPV vaccine (types 6, 11,16 and 18). Subsequent PCR sequencing with generic primers GP5-GP6 and further BLAST comparative analysis confirmed that genomic viral sequence in our case truly corresponded with HPV-32. This molecular misdiagnosis can be explained by the similarity between genomic sequences of both HPV-16 and -32 genotypes. At the 1-year follow up, we observed total clinical improvement and no recurrences of the disease. Complete healing in this case may correspond to a potential action of topical retinoid, imiquimod and the cross-protection mechanism of the quadrivalent HPV vaccine.

Focal epithelial hyperplasia associated with human papillomavirus 13 and common human leukocyte antigen alleles in a Turkish family.

BACKGROUND: Focal epithelial hyperplasia (FEH) is a rare and benign papillomatous disease of the oral cavity, which is closely associated with human papillomavirus (HPV) type 13 and 32. Genetic susceptibility to HPV infections are supported by recent studies involving the human leukocyte antigen system (HLA). In this report, we aimed to determine the clinicopathological features of a Turkish family with FEH and to detect the shared HLA DR and DQ types. METHODS: HPV DNA typing of tissue samples and HLA determination from blood samples of four family members were performed by polymerase chain reaction. RESULTS: Histopathological examination of all patients revealed acanthotic papillomatous epidermis, koilocytes, apoptotic keratinocytes, and mitosoid bodies. HPV13 was detected by polymerase chain reaction. HLA DQA1*0501, HLA DQB1*0302, and HLA DRB1*11 alleles were common in all family members. HLA DRB1*04 was detected in three of them. CONCLUSION: This report is the first step for the investigation of involvement of HLA types in the pathogenesis of Turkish patients with FEH.

Oral focal epithelial hyperplasia: report of three cases.

Focal epithelial hyperplasia or Heck's disease is an infrequent asymptomatic condition caused by human papillomavirus types 13 or 32 affecting the mucous membrane of the mouth and is commonly seen in young individuals. Firstly, it was described in Indians and Eskimos, but it exists in various populations. We present three cases of Heck's disease in an Afghan immigrant family group living in Iran that seem to have familial predominance. The disease was identified as oral focal epithelial hyperplasia on the basis of histopathologic and clinical findings. The lesions were reduced significantly after 4 months of good oral hygiene. Dentists should be familiar with the clinical manifestations of these types of lesions that affect the oral cavity. In fact, histopathologic assessment and clinical observation are necessary to establish the diagnosis.

The role of human papillomavirus in oral disease.

A wide range of human papillomavirus (HPV) genotypes have been detected in oral mucosa. Clinical infections with low-risk genotypes manifest as squamous papilloma, condyloma acuminatum, verruca vulgaris, or multifocal epithelial hyperplasia. Clinical infections with high-risk genotypes have been associated with malignant lesions. The most common genotype isolated from subclinical infection is HPV-16. A causal role for HPV in carcinogenesis of oral squamous carcinoma is minimal. Ongoing vaccination against HPV types 6, 11, 16, and 18 is expected to decrease the spread of infection and decrease the carcinogenic potential of HPV-16 in the oropharynx and oral cavity.

Focal epithelial hyperplasia in a Turkish family.

Focal epithelial hyperplasia (FEH) is a benign proliferative condition that is more frequently found in children of certain ethnic groups. Human papillomavirus (HPV) 13 and 32 genotypes has been consistently detected in these lesions. In this study a daughter, mother and father had FEH, and HPV 13 was shown by sequence analysis in the lesions of these patients. Cryotherapy was applied to the lesions and the lesions improved, but did not recover properly. In conclusion, HPV genotyping should be performed in FEH cases.

Human papillomavirus-32-associated focal epithelial hyperplasia accompanying HPV-16-positive papilloma-like lesions in oral mucosa.

Human papillomavirus infection can cause a variety of benign or malignant oral lesions, and the various genotypes can cause distinct types of lesions. To our best knowledge, there has been no report of 2 different human papillomavirus-related oral lesions in different oral sites in the same patient before. This paper reported a patient with 2 different oral lesions which were clinically and histologically in accord with focal epithelial hyperplasia and oral papilloma, respectively. Using DNA extracted from these 2 different lesions, tissue blocks were tested for presence of human papillomavirus followed by specific polymerase chain reaction testing for 6, 11, 13, 16, 18, and 32 subtypes in order to confirm the clinical diagnosis. Finally, human papillomavirus-32-positive focal epithelial hyperplasia accompanying human papillomavirus-16-positive oral papilloma-like lesions were detected in different sites of the oral mucosa. Nucleotide sequence sequencing further confirmed the results. So in our clinical work, if the simultaneous occurrences of different human papillomavirus associated lesions are suspected, the multiple biopsies from different lesions and detection of human papillomavirus genotype are needed to confirm the diagnosis.

Human papillomavirus and oral disease - emerging evidence: a review.

Human papillomavirus (HPV) infections have received considerable attention in recent years. Of the 120 or so known types of the virus, some cause a variety of benign wart-like lesions of the skin and genital and oral mucosae, whilst others are aetiologically associated with cervical and anogenital cancers. Recent epidemiologic evidence suggests that HPV may also be an independent risk factor for oropharyngeal cancer. In this context it has been suggested that HPV virus may modulate the process of carcinogenesis in some tobacco and alcohol induced oropharyngeal cancers and act as the primary oncogenic agent for inducing carcinogenesis among non-smokers. Dental practitioners have a major role in detecting all lesions of the oral mucosa caused, or possibly caused, by HPV. This paper briefly reviews the current state of knowledge of molecular and clinical aspects of HPV infections of the oral mucosa.

HPV oral lesions in HIV-infected patients: the impact of long-term HAART.

BACKGROUND: Since the introduction of highly active antiretroviral therapy (HAART), an increase in the frequency of human papillomavirus-associated oral lesions (HPV-OL) has been observed. Thus, the aim of this study was to determine the prevalence and factors associated with HPV-OL in Mexican HIV-infected patients, as well as its genotyping, in the HAART era. METHODS: In a cross-sectional study developed at an HIV/AIDS referral center in Mexico City, HIV-infected patients were consecutively included from 2004 to 2011. An oral exam was performed; lymphocyte CD4(+) count, HIV-viral load, CDC-stage, and HAART use were recorded. HPV-OL samples were taken for routine histopathological analysis (H-E) and HPV-DNA amplification/sequencing. Logistic regression models were performed and the interactions tested using the STATA software. RESULTS: Among 787 HIV patients, 55 (6.9%) showed HPV-OL. HPV-OLs were independently associated with age (≥40 years) and with a longer time of HAART use (≥12 months). The most frequent lesion was squamous cell papilloma in 22 (40%) cases, followed by multifocal epithelial hyperplasia in 15 (27.3%) cases. Labial mucosa was the most common site involved (56.4%). Of the sequences obtained, 65.4% corresponded to low risk and 11.5% to high risk. Mixed high- and low-risk infection were identified in 7.7% of the cases. CONCLUSIONS: Human papillomavirus-associated oral lesions were associated with older age and longer HAART use. All lesions were benign in nature and most of the HPV sequences corresponded to low-risk types. The rise of HPV-OLs in HIV patients on HAART may be related with the longer life expectancy of individuals with an impaired immune system rather than a direct effect of HAART.

Modelo de regresión logística binaria para el diagnóstico morfológico de lesiones por virus del papiloma humano (VPH) en la boca / Usefulness of Toki's morphological criteria for the diagnosis of oral lesions caused by human papillomavirus

Background: Oral lesions caused by human papillomavirus (HPV), share morphological features which may complicate their diagnosis. Aim: To analyze the usefulness of Toki's morphological criteria for the diagnosis of HPV lesions in cervix, in the diagnosis of oral lesions. Materials and Methods: Retrospective study of 355 oral lesions by HPV. The pathologic evaluation was carried out three times by the same examiner with a Kappa coefficient of 0.780 (p = 0.01). Toki's criteria scored the presence of acanthosis as 1, dyskeratosis as 1, koilocytosis as 4, basilar hyperplasia as 1, bi or multinucleated cells as 2 and papillomatosis as 1. The information was analyzed using χ² and binary logistic regression. Results: Fifty eight percent of cases (207) corresponded to Verruca Vulgaris (VV), 23% (80) to Multifocal Epithelial Hyperplasia (MEH), and 19% (68) to Condyloma Acuminatum (CA). According to Toki's criteria, 76/80 MEH lesions, 195/207 of VV and 67/68 of CA, had a score equal or greater than six. A logistic regression showed that dyskeratosis suggests the presence of MEH. The presence of acanthosis and dyskeratosis in HPV oral lesions are not useful criteria for the diagnosis of VV. No significant associations with CA were found. Conclusions: The morphological criteria studied do not predict their possible viral etiology and do not allow a differential diagnosis of the lesions. Therefore, polymerase chain reaction studies are required to identify high-risk HPVs or sexually transmitted viral lesions.

Focal epithelial hyperplasia (Heck's disease) in two Chinese females.

Focal epithelial hyperplasia, or Heck's disease, is a relatively rare virus-induced benign disease. To the best of the authors' knowledge it has not been reported in an ethnic Chinese population. The authors report two cases of focal epithelial hyperplasia (FEH) in Chinese patients, which were clinically and histologically in accord with FEH. In particular, the lesions in one case were located on the gingival mucosa, which is rarely affected by FEH. DNA extracted from paraffin-embedded specimens from the two patients was tested for the presence of human papilloma virus followed by specific polymerase chain reaction testing for 16, 18, 13, and 32 subtypes in order to confirm the clinical diagnosis.

[Usefulness of Toki's morphological criteria for the diagnosis of oral lesions caused by human papillomavirus]. / Modelo de regresión logística binaria para el diagnóstico morfológico de lesiones por virus del papiloma humano (VPH) en la boca.

BACKGROUND: Oral lesions caused by human papillomavirus (HPV), share morphological features which may complicate their diagnosis. AIM: To analyze the usefulness of Toki's morphological criteria for the diagnosis of HPV lesions in cervix, in the diagnosis of oral lesions. MATERIALS AND METHODS: Retrospective study of 355 oral lesions by HPV. The pathologic evaluation was carried out three times by the same examiner with a Kappa coefficient of 0.780 (p = 0.01). Toki's criteria scored the presence of acanthosis as 1, dyskeratosis as 1, koilocytosis as 4, basilar hyperplasia as 1, bi or multinucleated cells as 2 and papillomatosis as 1. The information was analyzed using χ² and binary logistic regression. RESULTS: Fifty eight percent of cases (207) corresponded to Verruca Vulgaris (VV), 23% (80) to Multifocal Epithelial Hyperplasia (MEH), and 19% (68) to Condyloma Acuminatum (CA). According to Toki's criteria, 76/80 MEH lesions, 195/207 of VV and 67/68 of CA, had a score equal or greater than six. A logistic regression showed that dyskeratosis suggests the presence of MEH. The presence of acanthosis and dyskeratosis in HPV oral lesions are not useful criteria for the diagnosis of VV. No significant associations with CA were found. CONCLUSIONS: The morphological criteria studied do not predict their possible viral etiology and do not allow a differential diagnosis of the lesions. Therefore, polymerase chain reaction studies are required to identify high-risk HPVs or sexually transmitted viral lesions.