Frequency of HPV detection in chagasic megaesophagus associated or not with esophageal squamous cell carcinoma

Abstract

<jats:title>Abstract</jats:title> <jats:p>Background: Chagasic megaesophagus (clinical manifestation of chagasic disease) has been reported as an etiological factor for squamous cell carcinoma of the esophagus, as well as the presence of human papillomavirus (HPV). Objective: We accessed the prevalence of HPV DNA in a series of squamous cell carcinomas of the esophagus associated or not with the chagasic megaesophagus, and within samples of chagasic megaesophagus without cancer. Data obtained was further correlated to the pathological clinical data of affected individuals. Methods: Retrospective study that used a total 92 samples tissue/biopsy specimens of formalin fixed and paraffin embedded tissues were retrospectively collected from the southeast region of Brazil from patients treated in three hospitals: Barretos Cancer Hospital, Barretos, São Paulo; Federal University of Triângulo Mineiro (UFTM), Uberaba, Minas Gerais; and São Paulo State University (UNESP), Botucatu, São Paulo. Cases were divided in three groups: i) 24 patients with chagasic megaesophagus associated with esophageal ESCC (CM/ESCC); ii) 37 patients with esophageal ESCC without chagasic megaesophagus (ESCC); iii) 31 patients with chagasic megaesophagus without esophageal ESCC (CM). Results: We detected a higher prevalence of high-risk HPVs in patients from both CM (12/31, 38.8%) and CM/ESCC groups (8/24, 33.3%), as compared to individuals of the ESCC group (6/37, 16.3%), although data was not statistically significant. We further observed that HPV-16 was more prevalent in patients of the ESCC (4/9, 44.5%) and CM/ESCC groups (2/8, 25.0%). In addition, some of these samples presented infection by multiple HPV types. High-risk HPVs detected were HPV-31, 45, 51, 53, 56, 66, and 73, of which the majority was identified in patients from the CM group. Furthermore, low-risk HPV-11 and HPV70 were identified in individuals from both ESCC and CM groups. Conclusion: This is the first report regarding the presence of HPV DNA in megaesophagus associated with esophageal squamous cell carcinoma. In the present study, HPV infection appears to be directly related to the development of esophageal squamous cell carcinoma in patients with chagasic megaesophagus. Further studies are warrantee to confirm and better understand the role of oncogenic HPV persistent infection in these patients.</jats:p>

Frequency of Human Papillomavirus Detection in Chagasic Megaesophagus Associated or Not with Esophageal Squamous Cell Carcinoma

“…Clinical-pathological and molecular features of the patients studied are described in Table 1 [22]. As previously reported by our group [33], most of the patients were men and under 60 years old.…”

“…It is known that infection by the protozoan Trypanosoma cruzi in the esophageal mucosa leads to several physiological changes that result in the development of CM [40,65,66]. In addition, individuals with CM have a higher risk of developing squamous cell carcinoma of the esophagus (3-8%) when compared to the general population; it is believed that this occurs due to the prolonged contact of food in the esophageal mucosa, increasing bacterial growth, and chemical irritation, resulting in chronic esophagitis [19,24,40].…”

“…We included only patients diagnosed with an image or histopathological proven CM with or without a positive serologic test for Chagas' disease; we also included patients with ESCC without CM serologic negative for Chagas' disease whose exams (image and histopathology) confirmed the malignant disease. Clinicalpathological variables of patients, as well as the molecular status of TP53 hotspot mutations and MSI phenotype, were previously reported from these individuals [22,33,34]. All clinical and pathological information was obtained through medical record's review.…”

“…These changes lead to the buildup of food, resulting in the development of megaesophagus [17]. Importantly, about 2-10% of individuals with CM will develop ESCC [19][20][21]; however, due to the scarcity of studies regarding the carcinogenic environment, the neoplastic mechanism leading to ESCC remains uncertain [22]. Nevertheless, it is believed that inflammation and chronic esophagitis may play an important role in the development of epithelial dysplasia and subsequently in cancer [23,24].…”