Epidemiological characterization of oral focal epithelial hyperplasia in brown howler monkeys (Alouatta guariba clamitans).

BACKGROUND: Oral focal epithelial hyperplasia (FEH) is an uncommon infection affecting humans, chimpanzees, bonobos, and howler monkeys. This study describes 10 cases of free-ranging brown howler monkeys (Alouatta guariba clamitans) diagnosed with FEH and Alouatta guariba Papillomavirus 1 (AgPV 1). METHODS: We analyzed demographic characteristics, rescue conditions, clinical and pathological findings, and species-specific behavior factors in these cases. The study assessed the frequency of occurrence and potential contributing factors of FEH and AgPV 1 infection. RESULTS: The frequency of FEH was 8.13%. Most affected howlers were adult or geriatric males with comorbidities or stressful conditions. Clinical and pathological observations were consistent with AgPV 1 infection. Species-specific behaviors and environmental stressors were identified as contributing factors. CONCLUSIONS: FEH associated with AgPV 1 affected mainly adult or geriatric males with ongoing comorbidities or stressful conditions. Further research is needed to understand these factors for effective management.

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.

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.

[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.

Human papillomavirus 13 in a Mexican Mayan community with multifocal epithelial hyperplasia: could saliva be involved in household transmission?

Multifocal epithelial hyperplasia (MEH) is a disease of the oral mucosa. Human papillomaviruses 13 and 32 have been detected in these lesions. We describe the epidemiology and clinical characteristics of patients with MEH in a rural community in the Mayan area of Mexico with 53 cases and 54 controls. Clinical and epidemiological data were collected through a direct interview. Oral cell samples were collected with a cytobrush. Subjects collected their own saliva sample in a sterile bottle. All samples were tested for HPV 13 and 32 by polymerase chain reaction using specific primers. Of the 53 patients and 54 healthy subjects, 56% were < 12 years old, 25% were males and 75% females. Evolution of the lesions was between two months and 17 years. The lesions affected lips, jugal mucosa, and tongue, 96% had multiple lesions. From 53 patients, fifty samples of oral cells and 31 samples of saliva were analyzed. HPV 13 was detected in 100% oral cell and 100% saliva samples studied. 16 healthy subjects were HVP 13 positive. A highly significant association of HPV 13 infection and MEH was found, as determined by chi square test (p = 0.00) Household transmission of HPV 13 may happen through saliva and the shared use of contaminated objects.

Multifocal epithelial hyperplasia in a community in the Mayan area of Mexico.

BACKGROUND: Multifocal epithelial hyperplasia is a pathology of the oral mucosa which has been reported in diverse ethnic groups. Human papillomavirus (HPV) types 13 and 32 DNA has been detected in these lesions. The aims of this paper are to describe the epidemiological and clinical characteristics of an outbreak in a rural community in the Mayan area of Mexico and to identify a possible route of transmission through saliva. METHODS: A cross-sectional study was conducted in Chemax (Yucatan, Mexico). Clinical and epidemiological data were obtained through direct interviews. Samples of oral cells and saliva were taken. HPV 13 and 32 were identified by polymerase chain reaction using specific primers. RESULTS: A total of 57 patients were studied, of whom 79.1% were aged <15 years, 38.6% were male, and 61.3% were female. The duration of lesions ranged from one month to 50 years. Lesions were located on the lips, jugal mucosa, and more frequently, the tongue. HPV 13 was found in all the patients and HPV 32 in none. A total of 42 saliva samples were positive for HPV 13. CONCLUSIONS: Human papillomavirus type 13 is involved in multifocal epithelial hyperplasia among the Mexican Mayan population. The presence of HPV 13 in cells from saliva, combined with poor hygiene behaviors, may explain the familial distribution of the pathology.

Focal epithelial hyperplasia caused by human papillomavirus 13.

Focal epithelial hyperplasia is a benign, papulo-nodular disease of the oral cavity. It is rare, affecting primarily Native American populations during childhood. It is closely associated with human papillomavirus 13 and 32. This report describes the diagnosis of 2 cases of focal epithelial hyperplasia in children from southern Guyana. The diagnosis was made using clinical criteria, polymerase chain reaction, and DNA sequencing.

Induction of focal epithelial hyperplasia in tongue of young bk6-E6/E7 HPV16 transgenic mice.

Squamous cell carcinoma (SCC) of the oral cavity is one of the most common neoplasms in the world. During the past 2 decades, the role of high-risk human papilloma virus (HR-HPV) has been studied and the data supporting HPV as a one of the causative agents in the development and progression of a sub-set of head and neck squamous cell carcinomas (HNSCC) has accumulated. In order to investigate the role of HR-HPV oncogene expression in early epithelial alterations in vivo, we produced transgenic mice expressing HPV16 early region genes from the promoter of the bovine keratin 6 gene (Tg[bK6-E6/E7]). In this article, we demonstrate that E6/E7 transgene was abundantly expressed and cellular proliferation was increased in the middle tongue epithelia of transgenic mice, and that in the same region young (27 weeks old) Tg[bK6-E6/E7] mice spontaneously developed histological alterations, mainly focal epithelial hyperplasia (FEH).

Hiperplasia epitelial focal: enfermedad de Heck / Focal epithelial hyperplasia: Heck´s disease

La hiperplasia epitelial focal (HEF) o enfermedad de Heck, es una afección de la mucosa bucal poco frecuente, producida por el virus del papiloma humano (HPV) subtipos 13 y 32, en un sujeto genéticamente predispuesto. Se presenta en indígenas americanos, afecta a ambos sexos y a edades tempranas. Se caracteriza por pápulas o nódulos múltiples en la cavidad bucal, especialmente en la mucosa labial, yugal y lingual. La evolución es variable y la transformación maligna es posible, pero excepcional. Comunicamos el caso de un paciente de padres bolivianos, con lesiones de un año de evolución, que fue tratado con terapia láser, con buenos resultados

Molecular and serological evidence of the epidemiological association of HPV 13 with focal epithelial hyperplasia: a case-control study.

BACKGROUND: Focal epithelial hyperplasia is a benign proliferative condition that is more frequently found in children of certain ethnic groups. Human papillomavirus 13 and 32 DNA has been consistently detected in these lesions. OBJECTIVE: To demonstrate the epidemiological association of HPV 13 with FEH in the Emberá-Chamí community of Antioquia, Colombia. METHODS: A population-based, case-control study was conducted. One hundred and thirty-eight children were screened and 17 clinical and histologically-confirmed cases were sex and age-matched with 27 controls. Biopsies from FEH lesions and mouth washes from controls were obtained for DNA analysis. HPV 13 DNA was identified using a previously described type-specific PCR test. HPV 13 VLPs were produced by cloning of L1 from the HPV 13 cloned genome and seroreactivity against HPV 13 VLPs of sera from cases and controls were evaluated by ELISA. RESULTS: Among the whole population the prevalence of FEH was 13%. One-hundred-percent of the cases and 29.6% of the controls were HPV 13 positive. There was a significant difference in HPV DNA status between cases and controls (one-tailed Fisher exact test: P<0.0001). Antibodies against HPV 13 VLPs were found in 58.8% of cases and in 33.3% of controls, this difference was not statistically significant (P=0.089 Fisher exact test). However, the median of the ODs of the ELISA positive sera of the cases was 0.596 (interquartile range: 0.5075-0.8245) versus 0.452 (interquartile range: 0.337-0.479) in the controls and this was significantly different (P=0.0041 Man-Whitney test). CONCLUSIONS: We demonstrated a risk for association of FEH with infection with HPV 13. The higher level of antibodies against HPV 13 VLPs in cases may suggest the requirement of higher viral load or viral persistence for disease development.

Oral focal epithelial hyperplasia: report of five cases.

Focal epithelial hyperplasia or Heck's disease is a rare contagious disease caused by human papillomavirus types 13 or 32, initially described among Native American populations. This condition is characterized by the occurrence of multiple small papules or nodules in oral cavity, especially on labial and buccal mucosa and tongue. This report describes the diagnosis of focal epithelial hyperplasia in five Central Amazonian Indians who sought treatment at the Amazonas State Foundation of Tropical Medicine (FMT-AM), using clinical criteria, polymerase chain reaction (PCR) and DNA sequencing.

Oral focal epithelial hyperplasia: report of five cases

Hiperplasia epitelial focal ou doença de Heck é uma rara doença contagiosa causada pelos papilomavírus tipo 13 e 32 que foi inicialmente descrita entre populações nativas americanas. Esta doença caracteriza-se pela ocorrência de pequenas e múltiplas pápulas ou nódulos na cavidade bucal, especialmente nos lábios, mucosa bucal e língua. Este artigo descreve o diagnóstico da hiperplasia epitelial focal em cinco indígenas da Amazônia Central que procuraram tratamento na Fundação de Medicina Tropical do Amazonas (FMT-AM) utilizando critérios clínicos, reação em cadeia de polimerase (PCR) e sequenciamento de DNA.

Extensive focal epithelial hyperplasia: case report.

Focal epithelial hyperplasia (FEH) is a rare benign lesion caused by human papillomavirus subtype 13 or 32. The condition occurs in numerous populations and ethnic groups. A higher incidence in close communities and among family members indicates infectious pathogenesis. A 21-year-old woman with FEH is described, in whom the lesions had persisted for 10 years. A literature review is also presented, with emphasis on manifestations in the oral mucosa and histopathological features.

Multifocal epithelial hyperplasia. Report of nine cases.

Multifocal epithelial hyperplasia (MEH) is also known as focal epithelial hyperplasia, Heck's disease or multifocal papillomavirus-induced epithelial hyperplasia. It is characterised by the presence of multiple lesions in the oral mucosa of children and it has been associated with the presence of the human papillomavirus. The aim of this study was to determine the clinico-pathological features of the cases diagnosed as MEH in the Service of Dermatology of the Hospital Manuel Gea González (SDHMGG). The files of the SDHMGG were reviewed and all cases diagnosed as MEH were retrieved. Nine MEH cases were found. Most of the patients were 20 year-old or younger (67%) and females were more commonly affected (78%). All patients presented multiple lesions and always, close relatives with similar lesions were found. Lesions were located most commonly in the buccal mucosa, lower lip and commissures. MEH is a soft tissue intraoral condition that needs treatment solely of the traumatised lesions or those with cosmetic problems. Remaining lesions will disappear with the age of the patients. It is suggested that this entity should be named multifocal epithelial hyperplasia since this name describes better the clinico-pathological and microscopic features of the disease.

Clinical, histopathological and virological findings in patients with focal epithelial hyperplasia from Colombia.

BACKGROUND: Focal epithelial hyperplasia (FEH) is a rare oral HPV-related disease, highly prevalent in certain ethnic communities. A previous study found 7.5% prevalence among school children from the Indian community Embera-Chami in Colombia. OBJECTIVE: To determine the prevalence and Human Papillomavirus (HPVs)-type in children with FEH. MATERIALS AND METHODS: One hundred and thirty-eight students were screened. All FEH samples were HPV-tested by two PCR-based systems. RESULTS: We identified 18 FEH cases. beta-globin amplification was obtained in 15 cases and nine were HPV-55-positive by the HPV-PCR-hybridization method. Nine cases (50%) were HPV-13-positive by the GP5+/GP6+-based method. Twelve cases (80%) were HPV-positive by one or the other method. Forty-four percent and 88% of interviewed parents reported family histories of FEH and toothbrush sharing, respectively. CONCLUSIONS: Human Papillomavirus-DNA was identified in the majority of FEH cases and HPV-13 was the only genotype involved. Frequent familiar infection suggests interfamiliar transmission, genetic predisposition or infection susceptibility among family members.

[Human papillomavirus (HPV) infection and its relation with squamous cell carcinoma of the mouth and oropharynx]. / Correlação da infecção viral pelo papilomavírus humano com as lesões papilomatosas e o carcinoma epidermóide na boca e orofaringe.

OBJECTIVE: To establish a connection between infection by the human papilloma virus (HPV) and development of malignant (squamous cell carcinoma) and benign lesions (epithelial hyperplasia papillomatosis and papilloma) of the oral cavity and oropharynx. METHOD: A retrospective study of 66 blades and paraffin blocks with biopsy tissue fixed with formalin. This material, collected in 2002, refers to a group of 44 men (66.7%) and 22 women (33.3%) with ages ranging from 11 to 100 years, with confirmed diagnoses of squamous cell carcinoma in 38 cases, of epithelial hyperplasia papillomatosis in 20 cases and of papillomas in 8 cases. This material was analyzed by immunohistochemistry and the presence of viral DNA in the biopsy samples was determined. RESULTS: Presence of the viral DNA (HPV) in 16 of the 38 cases of carcinoma (42.5%), 19 in 20 cases of hyperplasia (95%) and 8 in 8 cases of papilloma (100%) was detected. CONCLUSION: The samples in this study show the predominant incidence of the HPV in the epithelial hyperplasia papillomatosis and papilloma in relation to squamous cell carcinoma. This last lesion, on the other hand, did not show statistical correlation to the HPV.

Association of HLA-DR4 (DRB1*0404) with human papillomavirus infection in patients with focal epithelial hyperplasia.

OBJECTIVES: To determine gene frequencies of HLA-DR alleles in 22 Mexican patients with focal epithelial hyperplasia and compare them with those present in ethnically matched healthy subjects, as well as to determine the types of human papillomavirus present in the lesions. DESIGN: Prospective and retrospective observational study. SETTING: Dermatology outpatient clinic in a general hospital. PATIENTS: Twenty-two patients with clinically and histologically confirmed focal epithelial hyperplasia seen within a 10-year period. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Results of high-resolution DNA typing for HLA-DR alleles and biopsy for viral typing. RESULTS: HLA-DR4 (DRB1*0404) was significantly increased (P<.001; odds ratio, 3.9; 95% confidence interval, 1.86-8.03). Seventeen (85%) of 20 patients had human papillomavirus subtype 13. The data on human papillomavirus differed from reports elsewhere that described association with human papillomavirus type 32. CONCLUSIONS: The HLA-DRB1*0404 allele suggests that Amerindian populations are at risk, and in this group, the Mexican population studied was affected only by human papillomavirus type 13.