Mahnaz Fatahzadeh

The Oral Cavity Contains Abundant Known and Novel Human Papillomaviruses From the Betapapillomavirus and Gammapapillomavirus Genera

BACKGROUND Human papillomaviruses (HPVs) primarily sort into 3 genera: Alphapapillomavirus (α-HPV), predominantly isolated from mucosa, and Betapapillomavirus (β-HPV) and Gammapapillomavirus (γ-HPV), predominantly isolated from skin. HPV types might infect body sites that are different from those from which they were originally isolated. METHODS We investigated the spectrum of HPV type distribution in oral rinse samples from 2 populations: 52 human immunodeficiency virus (HIV)-positive men and women and 317 men who provided a sample for genomic DNA for a prostate cancer study. HPV types were detected with the MY09/MY11 and FAP59/64 primer systems and identified by dot blot hybridization and/or direct sequencing. RESULTS Oral rinse specimens from 35 (67%) of 52 HIV-positive individuals and 117 (37%) of 317 older male participants tested positive for HPV DNA. We found 117 type-specific HPV infections from the HIV-positive individuals, including 73 α-HPV, 33 β-HPV, and 11 γ-HPV infections; whereas, the distribution was 46 α-HPV, 108 β-HPV, and 14 γ-HPV infections from 168 type-specific infections from the 317 male participants. CONCLUSIONS The oral cavity contains a wide spectrum of HPV types predominantly from the β-HPV and γ-HPV genera, which were previously considered to be cutaneous types. These results could have significant implications for understanding the biology of HPV and the epidemiological associations of HPV with oral and skin neoplasia.

Kaposi sarcoma: review and medical management update

Despite recent advances in our understanding of pathogenic mechanisms involved, the true nature of Kaposi sarcoma remains an enigma. Four clinical variants have been described for the disease, differing in natural history, site of predilection, and prognosis. All forms of Kaposi sarcoma may manifest in the oral cavity and Kaposi sarcoma-associated virus appears essential to development of all clinical variants. The spectrum of therapeutic strategies is broad and selection of appropriate intervention mandates a thorough understanding of disease spread and the patients symptomatology, as well as risks and benefits of therapy. This article provides an overview of epidemiology, subtypes, clinical course, pathogenesis, and management strategies for Kaposi sarcoma.

Oral Kaposi's sarcoma: a review and update

Kaposis sarcoma (KS) is an important mucocutaneous neoplasm with four well‐known clinicopathologic types. Involvement of the oral cavity may be seen in all variants but is most common with AIDS‐KS. The latter may signal undiagnosed HIV infection. Its common association with disseminated disease has potentially important diagnostic and therapeutic implications. Oral KS (OKS) most often affects the hard and soft palate, gingiva, and dorsal tongue with plaques or tumors of coloration ranging from non‐pigmented to brownish‐red or violaceous. Its involvement ranges from an incidental finding to proliferative tumor formation that interferes with mastication. OKS needs to be distinguished clinically from other entities, including pyogenic granuloma, hemangioma, bacillary angiomatosis, and gingival enlargement caused by cyclosporine, a drug frequently used in recipients of organ transplantation. KS may flare as part of the immune reconstitution inflammatory syndrome in HIV patients or develop in the context of iatrogenic immunosuppression. Management, which may depend upon a variety of factors including the clinicopathologic type of KS and results of staging, ranges from no treatment to local measures such as intralesional vinblastine or systemic administration of cytotoxic chemotherapy for disseminated disease. Modification of immunosuppressive regimens often helps control post‐transplant OKS but enhances the risk of graft rejection. Screening donors and recipients of organ transplants for HHV‐8, with prophylactic treatment if infected as well as institution of sirolimus early after transplantation, are proposed strategies aimed at preventing post‐transplant OKS.

Activity of Potent and Selective Host Defense Peptide Mimetics in Mouse Models of Oral Candidiasis

ABSTRACT There is a strong need for new broadly active antifungal agents for the treatment of oral candidiasis that not only are active against many species of Candida, including drug-resistant strains, but also evade microbial countermeasures which may lead to resistance. Host defense peptides (HDPs) can provide a foundation for the development of such agents. Toward this end, we have developed fully synthetic, small-molecule, nonpeptide mimetics of the HDPs that improve safety and other pharmaceutical properties. Here we describe the identification of several HDP mimetics that are broadly active against C. albicans and other species of Candida, rapidly fungicidal, and active against yeast and hyphal cultures and that exhibit low cytotoxicity for mammalian cells. Importantly, specificity for Candida over commensal bacteria was also evident, thereby minimizing potential damage to the endogenous microbiome which otherwise could favor fungal overgrowth. Three compounds were tested as topical agents in two different mouse models of oral candidiasis and were found to be highly active. Following single-dose administrations, total Candida burdens in tongues of infected animals were reduced up to three logs. These studies highlight the potential of HDP mimetics as a new tool in the antifungal arsenal for the treatment of oral candidiasis.

Oral Human Papillomavirus Detection in Older Adults Who Have Human Immunodeficiency Virus Infection

OBJECTIVE To evaluate reproducibility of oral rinse self-collection for human papillomavirus (HPV) detection and investigate associations between oral HPV, oral lesions, immune and sociodemographic factors, we performed a cross-sectional study of older adults with human immunodeficiency virus (HIV) infection. STUDY DESIGN We collected oral rinse samples from 52 subjects at 2 different times of day, followed by an oral examination and interview. We identified HPV with the use of polymerase chain reaction platforms optimized for detection of mucosal and cutaneous types. RESULTS Eighty-seven percent of individuals had oral HPV, of which 23% had oncogenic alpha, 40% had nononcogenic alpha, and 46% had beta or gamma HPV. Paired oral specimens were concordant in all parameters tested. Significant associations observed for oral HPV with increased HIV viral load, hepatitis C seropositivity, history of sexually transmitted diseases, and lifetime number of sexual partners. CONCLUSIONS Oral cavity may be a reservoir of subclinical HPV in older adults who have HIV infection. Understanding natural history, transmission, and potential implications of oral HPV warrants further investigations.

Manifestation of acute monocytic leukemia in the oral cavity: a case report

This case history describes a 26-year-old male with gingival bleeding who presented for care and was treated accordingly. Within a week he developed signs and symptoms of systemic disease and upon further investigation, he was diagnosed with acute monocytic leukemia to which he succumbed within 72 hours. The implications of gingival bleeding are discussed, and the necessity to consider systemic disease in the differential diagnosis is emphasized.

Oral Psoriasis: An Overlooked Enigma.

Although cutaneous psoriasis is common, the existence of its manifestations in the oral cavity has been questioned. The definitive diagnosis of oral psoriasis can be challenging due to the variability of presentations, and overlapping clinical and histological features with a number of other conditions as well as the lack of consensus. We review oral psoriasis, noting its variable clinical appearance, delineate the differential diagnosis, and discuss management strategies.

Oral Human Papillomavirus Infection and Oral Lesions in HIV-Positive and HIV-Negative Dental Patients

We evaluated the risk factors associated with oral human papillomavirus (HPV) infection and oral lesions in 161 human immunodeficiency virus (HIV)-positive patients and 128 HIV-negative patients presenting for oral examination at 2 urban healthcare centers. Patients were interviewed on risk factors and provided oral-rinse samples for HPV DNA typing by polymerase chain reaction. Statistical associations were assessed by logistic regression. Oral HPV was prevalent in 32% and 16% of HIV-positive patients and HIV-negative patients, respectively, including high-risk HPV type 16 (8% and 2%, respectively; P = .049) and uncommon HPV types 32/42 (6% and 5%, respectively; P = .715). Among HIV-negative patients, significant risk factors for oral HPV included multiple sex partners (≥21 vs ≤5; odds ratio [OR], 9.1; 95% confidence interval [CI], 1.7-49.3), heavy tobacco smoking (>20 pack-years vs none; OR, 9.2; 95% CI, 1.4-59.4), and marijuana use (OR, 4.0; 95% CI, 1.3-12.4). Among HIV-positive patients, lower CD4(+) T-cell count only was associated with oral HPV detection (≤200 vs ≥500 cells/mm(3); OR, 4.5; 95% CI, 1.3-15.5). Detection of high-risk HPV was also associated with concurrent detection of potentially cancerous oral lesions among HIV-negative patients but not among HIV-positive patients. The observed risk factor associations with oral HPV in HIV-negative patients are consistent with sexual transmission and local immunity, whereas in HIV-positive patients, oral HPV detection is strongly associated with low CD4(+) T-cell counts.

Oral squamous cell carcinoma in a patient with keratitis-ichthyosis-deafness syndrome: a rare case

Keratitis-ichthyosis-deafness (KID) syndrome is a rare form of ectodermal dysplasia with significant visual and auditory impairment. Pathogenesis involves a mutation in the GJB2 gene, which encodes connexin-26, a protein in the epithelial gap junctions thought to be involved in the differentiation of ectodermally derived tissues. Affected patients are also at increased risk for the epithelial malignancies. To our knowledge, nearly 100 cases of KID syndrome, including 19 with squamous cell carcinoma (SCC) complications, have been reported worldwide. We report here a patient with KID syndrome who developed an ulcerative oral lesion causing him significant discomfort; he was subsequently diagnosed with oral SCC. We review the clinical presentation and symptomatology, including those affecting the oral cavity for this syndrome and highlight the importance of multidisciplinary collaboration and life-long screening aimed at prevention of the evolving complications.

Podoplanin emerges as a functionally relevant oral cancer biomarker and therapeutic target

Oral cancer has become one of the most aggressive types of cancer, killing 140,000 people worldwide every year. Current treatments for oral cancer include surgery and radiation therapies. These procedures can be very effective; however, they can also drastically decrease the quality of life for survivors. New chemotherapeutic treatments are needed to more effectively combat oral cancer. The transmembrane receptor podoplanin (PDPN) has emerged as a functionally relevant oral cancer biomarker and chemotherapeutic target. PDPN expression promotes tumor cell migration leading to oral cancer invasion and metastasis. Here, we describe the role of PDPN in oral squamous cell carcinoma progression, and how it may be exploited to prevent and treat oral cancer.