Hypopharyngeal Ulcers in COVID-19: Histopathological and Virological Analyses - A Case Report.

In coronavirus disease 2019 (COVID-19), ulcerative lesions have been episodically reported in various segments of the gastrointestinal (GI) tract, including the oral cavity, oropharynx, esophagus, stomach and bowel. In this report, we describe an autopsy case of a COVID-19 patient who showed two undiagnosed ulcers at the level of the anterior and posterior walls of the hypopharynx. Molecular testing of viruses involved in pharyngeal ulcers demonstrated the presence of severe acute respiratory syndrome - coronavirus type 2 (SARS-CoV-2) RNA, together with herpes simplex virus 1 DNA. Histopathologic analysis demonstrated full-thickness lympho-monocytic infiltration (mainly composed of CD68-positive cells), with hemorrhagic foci and necrosis of both the mucosal layer and deep skeletal muscle fibers. Fibrin and platelet microthrombi were also found. Cytological signs of HSV-1 induced damage were not found. Cells expressing SARS-CoV-2 spike subunit 1 were immunohistochemically identified in the inflammatory infiltrations. Immunohistochemistry for HSV1 showed general negativity for inflammatory infiltration, although in the presence of some positive cells. Thus, histopathological, immunohistochemical and molecular findings supported a direct role by SARS-CoV-2 in producing local ulcerative damage, although a possible contributory role by HSV-1 reactivation cannot be excluded. From a clinical perspective, this autopsy report of two undiagnosed lesions put the question if ulcers along the GI tract could be more common (but frequently neglected) in COVID-19 patients.

Laryngopharyngeal Reflux Is a Potential Risk Factor for Juvenile-Onset Recurrent Respiratory Papillomatosis.

INTRODUCTION: Human papillomavirus (HPV) causes juvenile-onset recurrent respiratory papillomatosis (JORRP). Although HPV is common in children, the prevalence of JORRP is low. It is likely that other factors contribute to the pathogenesis of JORRP, during either activation or reactivation of a latent HPV infection. There is evidence that laryngopharyngeal reflux (LPR) might be such a risk factor for adult-onset recurrent respiratory papillomatosis. This study investigated if LPR might also be a risk factor for JORRP. MATERIALS AND METHODS: Children with JORRP of the larynx that required microlaryngoscopy at a tertiary referral hospital were included in this prospective case-series study from November 2015 to November 2017. Using immunohistochemistry, HPV infection and pepsin associated with LPR were diagnosed from laryngeal biopsies. RESULTS: Eleven children (aged 4-14 years) were analyzed. No patient had a history of immunodeficiency or tobacco smoke exposure. All patients underwent at least three previous surgeries due to JORRP and had been vaccinated against HPV in the past. Five children were treated using antivirotics and immunomodulators. The only known maternal risk factor was that three mothers were primiparous. All 11 samples were infected with HPV (type 6 or 11). Pathologic LPR was diagnosed in 5/11 children (45.5%). CONCLUSION: LPR may be a risk factor for JORRP, contributing to its development by activating or reactivating a latent HPV infection. Results are in accordance with those from our previous study in adults.

Low human papillomavirus prevalence in head and neck cancer: results from two large case-control studies in high-incidence regions.

BACKGROUND: Recent studies support an important role for human papillomavirus (HPV) in a subgroup of head and neck squamous cell carcinomas (HNSCC). We have evaluated the HPV deoxyribonucleic acid (DNA) prevalence as well as the association between serological response to HPV infection and HNSCC in two distinct populations from Central Europe (CE) and Latin America (LA). METHODS: Cases (n = 2214) and controls (n = 3319) were recruited from 1998 to 2003, using a similar protocol including questionnaire and blood sample collection. Tumour DNA from 196 fresh tissue biopsies was analysed for multiple HPV types followed by an HPV type-specific polymerase chain reaction (PCR) protocol towards the E7 gene from HPV 16. Using multiplex serology, serum samples were analysed for antibodies to 17 HPV types. Statistical analysis included the estimation of adjusted odds ratios (ORs) and the respective 95% confidence intervals (CIs). RESULTS: HPV16 E7 DNA prevalence among cases was 3.1% (6/196), including 4.4% in the oropharynx (3/68), 3.8% in the hypopharynx/larynx (3/78) and 0% among 50 cases of oral cavity carcinomas. Positivity for both HPV16 E6 and E7 antibodies was associated with a very high risk of oropharyngeal cancer (OR = 179, 95% CI 35.8-899) and hypopharyngeal/laryngeal cancer (OR = 14.9, 95% CI 2.92-76.1). CONCLUSIONS: A very low prevalence of HPV DNA and serum antibodies was observed among cases in both CE and LA. The proportion of head and neck cancer caused by HPV may vary substantially between different geographical regions and studies that are designed to evaluate the impact of HPV vaccination on HNSCC need to consider this heterogeneity.

Clinicopathological consultation. Lymphoepithelial carcinoma of the larynx hypopharynx, and trachea.

Lymphoepithelial carcinoma of the larynx, hypopharynx, and trachea is a rare neoplasm composed of large, poorly differentiated, nonkeratinized cells intermingled with small nonneoplastic lymphocytes and plasma cells. It is histologically similar to its more common counterpart occurring in the nasopharynx. In contrast to nasopharyngeal carcinoma, most cases have not been associated with Epstein-Barr virus (EBV), although rare cases have been reported to be EBV-positive. The diagnosis often requires immunohistochemistry or electron microscopy for confirmation. The neoplasm seems to behave in a fashion reminiscent of nasopharyngeal carcinoma. Lymph node metastasis occurs in the majority of patients, and eventual visceral dissemination occurs in one fourth. Radiotherapy is the main treatment for the primary tumor and regional metastases, but chemotherapy is indicated for more advanced disease. The initial stage is the primary determinant of prognosis. Death from disease occurs in about one third of patients.

[The relation between human papilloma virus and cellular DNA content in epidermoid carcinoma of the head and neck]. / Relación entre el virus del papiloma humano y el contenido celular de ADN en los carcinomas epidermoides de cabeza y cuello.

The relation between the presence of gene sequences of human papilloma virus (HPV) and the development of abnormalities in cellular DNA content was analyzed in 31 squamous-cell carcinomas of the head and neck. The integration of HPV types 16 and 6b by PCR and DNA content was studied by flow cytometry in 31 specimens from patients with squamous-cell carcinoma of the head and neck. Eighteen (58%) cases were aneuploid. HPV DNA was present in seven tumors (22.5%), five of then HPV-6b and two of them HPV-16. Aneuploidy correlated with poorly differentiated tumors. No correlation was found between HPV integration and either cellular DNA content or the degree of histological tumor differentiation. Therefore, the presence of HPV gene sequences did not seem to be associated with a higher incidence of aneuploidy in squamous-cell carcinoma of the head and neck.

Human papilloma viruses in the human hypopharynx.

The possible association of human papilloma viruses (HPV) with laryngopharyngeal squamous cell carcinoma is under investigation. Recent work suggests regional differences in the prevalence of HPV infection in the hypopharynx. The present study investigates the prevalence of HPV in tissue obtained from a series of piriform fossae. Piriform fossa epithelium was harvested from 12 autopsy cases free of local disease. DNA was obtained by SDS/Proteinase K digestion. Evidence of HPV infection was documented by the polymerase chain reaction using oligonucleotide primers complementary to sequences in the E6 region of HPV types 11, 16 and 18. All the specimens were positive for beta-globin. HPV11 was isolated from two patients. None were positive for HPV16 or HPV18. An 18% prevalence rate for HPV11 in the normal human hypopharynx was found.

Human papillomavirus type 16 DNA detected by the polymerase chain reaction in non-cancer tissues of the head and neck.

Cancer-free tissues from various anatomical subsites in the head and neck were examined by the polymerase chain reaction (PCR) for the incidence of human papillomavirus (HPV) types 16 and 18. We detected HPV-16 DNA in 9 of 103 samples (8.7%), including specimens from the paranasal sinuses, tonsil, hypopharynx and larynx. However, no HPV-16/18 DNA was detected by Southern hybridization in these 9 samples. The significance of the presence of HPV-16 DNA in non-cancer tissues is still unknown, but PCR detection only of high-risk HPV DNA in head and neck cancer should be evaluated cautiously because of its ubiquity in this region.