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

Araújo, Maria Christina Barbosa de; Rubira-Bullen, Izabel Regina Fischer; Santos, Carlos; Dionísio, Thiago José; Bonfim, Carmem; Marco, Laura De; Gillio-Tos, Anna; Merletti, Franco

doi:10.1111/j.1601-0825.2011.01803.x

Cited by 36 publications

(36 citation statements)

References 31 publications

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“…15,20,23 In the present study there was a significant increase in NA and CA and a decrease in the NA/CA ratio of epithelial cells for the FA group when compared to the C group. The increase in the NA and CA could be associated with chronic anaemia caused by medullar aplasia.…”

Section: Discussionsupporting

confidence: 46%

“…FA is a rare disorder resulting from autosomal or rarely X-linked recessive inheritance of mutations in 20 Manifestations of FA appear in the first decade of life and include various malformations such as short stature, abnormality of the thumbs, microcephaly, café au lait hypopigmented spots, renal malformation, and growth retardation. 21 Patients with FA that underwent haematopoietic cell transplantation have an increased susceptibility to the development of squamous cell carcinomas (SCC) of the head and neck compared to FA patients.…”

Section: Discussionmentioning

confidence: 99%

“…22 The tongue is the prevalent site for SCC development in the oral cavity. 20 Thus intraoral examinations are relevant for detecting dysplasia. This justifies the choice of the tongue as the collection area in this study.…”

Section: Discussionmentioning

confidence: 99%

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Exfoliative Cytology in the Oral Mucosa of Patients with Fanconi Anaemia: A Morphometric Approach

Machado¹,

D'Agulham²,

Chaiben³

et al. 2017

J Dent Indones

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Patients with Fanconi anaemia (FA) are prone to develop squamous cell carcinomas at an early age. Exfoliative cytology can be used to detect changes to the health of the oral mucosa. Objective: The aim of this study was to evaluate morphometrical and morphological changes using exfoliative cytology and to analyse and quantify the proliferative activity using silver nucleolar organiser regions (AgNOR) in epithelial cells of the tongue in FA patients, after haematopoietic stem cell transplantation (HSCT). Methods: Oral smears were collected from the tongues of 20 FA children and adolescents after haematopoietic stem cell transplantation (FA) and 20 healthy children (C) using exfoliative cytology. The smears were stained using the Papanicolaou technique and silver impregnation. The cells were morphologically analysed and the nuclear area (NA), the cytoplasmic area (CA), and the nucleusto-cytoplasm area ratio (NA/CA) were calculated. Results: Mean values for the FA and C groups were: NA (71.85 and 55.21µm²; p< 0.01); CA (2127.48 and 1441.61µm²; p< 0.01); NA/CA (0.03 and 0.04; p< 0.01), respectively. A significant increase in the NA and CA for the FA group (p< 0.01) was seen, and an alteration in the NA/CA ratio. No morphological differences were found between the groups. Class I smears were predominant in both groups. No differences were found between the groups for the mean values of AgNORs per nucleus. Conclusion: This study suggests that morphological changes occurred in the oral epithelium cells of children and adolescents with Fanconi anaemia when subjected to HSCT.

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Section: Discussionsupporting

confidence: 46%

Section: Discussionmentioning

confidence: 99%

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Exfoliative Cytology in the Oral Mucosa of Patients with Fanconi Anaemia: A Morphometric Approach

Machado¹,

D'Agulham²,

Chaiben³

et al. 2017

J Dent Indones

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“…We have previously reported that HPV-immortalized FA keratinocytes form hyperplastic epithelium in an organotypic raft culture system compared to complemented cells (36,53). Furthermore, several studies have implicated FA in the increased incidence and aggressiveness of HPV-induced mouse models of cancer (54)(55)(56), and there is controversial evidence that HPV plays a role in the increased incidence of head, neck, and anogenital tumors in FA patients (57)(58)(59)(60). The effects of E6 and E7 on somatic reprogramming were characterized in a previous study, which found that both E6 and E7, alone and in combination, promoted reprogramming by preventing senescence (9).…”

Section: Discussionmentioning

confidence: 99%

High-Risk Human Papillomavirus E6 Protein Promotes Reprogramming of Fanconi Anemia Patient Cells through Repression of p53 but Does Not Allow for Sustained Growth of Induced Pluripotent Stem Cells

Chlon

Hoskins

Mayhew

et al. 2014

J Virol

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DNA repair plays a crucial role in embryonic and somatic stem cell biology and cell reprogramming. The Fanconi anemia (FA) pathway, which promotes error-free repair of DNA double-strand breaks, is required for somatic cell reprogramming to induced pluripotent stem cells (iPSC). Thus, cells from Fanconi anemia patients, which lack this critical pathway, fail to be reprogrammed to iPSC under standard conditions unless the defective FA gene is complemented. In this study, we utilized the oncogenes of high-risk human papillomavirus 16 (HPV16) to overcome the resistance of FA patient cells to reprogramming. We found that E6, but not E7, recovers FA iPSC colony formation and, furthermore, that p53 inhibition is necessary and sufficient for this activity. The iPSC colonies resulting from each of these approaches stained positive for alkaline phosphatase, NANOG, and Tra-1-60, indicating that they were fully reprogrammed into pluripotent cells. However, FA iPSC were incapable of outgrowth into stable iPSC lines regardless of p53 suppression, whereas their FA-complemented counterparts grew efficiently. Thus, we conclude that the FA pathway is required for the growth of iPSC beyond reprogramming and that p53-independent mechanisms are involved. IMPORTANCEA novel approach is described whereby HPV oncogenes are used as tools to uncover DNA repair-related molecular mechanisms affecting somatic cell reprogramming. The findings indicate that p53-dependent mechanisms block FA cells from reprogramming but also uncover a previously unrecognized defect in FA iPSC proliferation independent of p53.

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“…Pode haver pigmentação da mucosa jugal, língua e palato, atrofia das papilas linguais, redução do fluxo salivar. As alterações radiográficas mais frequentes são microdontia generalizada, ausência de dentes por extrações e agenesias, transposições e supranumerários (ACIKGOZ et al, 2005;DE ARAUJO et al, 2007;TEKCICEK et al, 2007;DE ARAUJO et al, 2011;SHETTY et al, 2011 (STOOPLER et al, 2007;ISLAM et al, 2011). Na literatura investigada, as alterações estomatológicas mais frequentes nos pacientes em preparo para TCTH foram gengivite, acúmulo de biofilme, cálculo dentário, periodontite com bolsas profundas e perda significativa de osso alveolar, alto índice de cárie, redução de fluxo salivar, restaurações com infiltrações necessitando de retratamento, lesões periapicais, raízes residuais, dentes parcialmente irrompidos, mucosite, dor relacionada à articulação têmporo-mandibular, infecções oportunistas por fungos e vírus, infiltrado leucêmico gengival, petéquias, equimoses, língua saburrosa, úlceras traumáticas infectadas, erosão dental, hiperplasia ou hipertrofia gengival, alterações oclusais e na formação dos dentes após quimioterapia na infância (LUCAS et al, 1998;GRABER et al, 2001;MELKOS et al, 2003;VAUGHAN et al, 2005b;YAMAGATA et al, 2006;BRENNAN et al, 2008;DA SILVA SANTOS et al, 2008;DUREY et al, 2009;BOER et al, 2010;HONG et al, 2010;LAAKSONEN et al, 2011;PALMASON et al, 2011;GURGAN et al, 2012;HERNANDEZ-FERNANDEZ et al, 2012).…”

Section: Doenças Onco-hematológicasunclassified

Alterações estomatológicas de pacientes em preparo para transplante de células-tronco hematopoiéticas

Araújo¹

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disponibilidade, por abrir meus olhos para uma nova e dinâmica Odontologia, me levando a questionar e aprender a desaprender conceitos e protocolos. Agradeço as oportunidades concedidas, as ocasiões em que trabalhamos juntos, os exemplos de dedicação familiar e profissional e o esmero no cuidado com os pacientes.Um verdadeiro educador, que transmite muito mais que informação científica. (61%) men and 39 (39%) women with a median age of 39 years. The most frequent underlying diseases were acute lymphoblastic leukemia (20%) and acute myeloid leukemia (19%). It was found that 45% of patients had some stomatological alterations. The most prevalent were tongue coating, petechiae, bruising and dry lips. AGRADECIMENTOSPeriodontal disease was found in 62% of patients. The most common manifestations were gingival bleeding among young patients and the more severe forms of periodontitis occurred after 35 years. The caries activity was high (DMFT=14.04), only 09 patients were caries free and 14% of patients had indication for extraction.The overall mean of OHIP-14 was very low (4.62), however there was correlation with the presence of severely compromised teeth due to caries and periodontal disease (p<0.05), indicating a significant impact on quality of life. The most impacting factors were caries activity (p<0.05), restorations with caries (p<0.05) and edentulism (p<0.05). In severe cases with indication for extraction, the impact was significant in psychological distress (p<0.05), psychological incapacity (p<0.01) and deficiency (p<0.01), the greatest degree of impairment of quality of life. We conclude that patients referred for HSCT have several stomatological alterations. Only the cases of aplastic anemia have oral manifestations of primary disease. However, the frequency of gingivitis, periodontitis, and caries activity were high, revealing shortage in dental support during the patient preparation in their hometowns. The impact of oral health problems on quality of life is weak, but in severe cases there is psychological impairment.

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

Abstract: 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.

Cited by 36 publications

References 31 publications

Exfoliative Cytology in the Oral Mucosa of Patients with Fanconi Anaemia: A Morphometric Approach

Exfoliative Cytology in the Oral Mucosa of Patients with Fanconi Anaemia: A Morphometric Approach

High-Risk Human Papillomavirus E6 Protein Promotes Reprogramming of Fanconi Anemia Patient Cells through Repression of p53 but Does Not Allow for Sustained Growth of Induced Pluripotent Stem Cells

Alterações estomatológicas de pacientes em preparo para transplante de células-tronco hematopoiéticas

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