Oncocytic variant of sialadenoma papilliferum - a rare salivary gland tumor: A case report.

Background: Sialadenoma papilliferum (SP) is a rare minor salivary gland neoplasm that accounts for less than 1% of all salivary gland tumors. The tumor typically affects older people, presenting most commonly as a slow-growing tumor of the hard palate, although other anatomical subsites, comprising the oral cavity and parotid glands, have also been reported. Case Report: We report a SP occurring in a 90-year-old female. The patient described feeling a nodule on her palate for several years. The lesion was painless and clinically resembled a round craterlike ulceration of diameter 3 mm. The excisional biopsy was diagnosed histologically as SP. Here, we report the clinicopathological and radiological findings of palatal SP. Conclusions: SP is a rare, benign salivary gland neoplasm, and there are only a few cases described in the literature. Although mostly benign, malignant transformation can occur and should prompt the clinician to ensure complete removal of the tumor tissue. Key words:Sialadenoma papilliferum, minor salivary gland tumor, histopathology, oral pathology, case report.

Oral Squamous Cell Carcinoma in a Patient with Fanconi Anemia.

Fanconi anemia (FA) is a rare autosomal recessive genetic disorder characterized by different types of malformations, skin lesions, bone marrow failure, and increased risk for both hematological malignancies and solid tumors, especially head and neck squamous cell carcinomas (HNSCC). FA patients may also display a low tolerance to oncologic treatments. The authors present a case of mandibular squamous cell carcinoma in a young FA patient. Because of the aggressive nature of the SCC and complex treatment options, we recommend a strict lifelong follow-up for all FA patients to detect early changes in the oral mucosa.

Assessment of Craniomaxillofacial Injuries After Electric Scooter Accidents in Turku, Finland, in 2019.

PURPOSE: Since the introduction of rental electric scooters (ESs), clinicians have increasingly encountered facial trauma patients whose injuries were caused by ES use. Despite this fact, few studies have analyzed these patients, particularly in Nordic countries, where the climate may cause additional challenges. We hypothesized that ESs have caused several facial trauma cases in Turku, Finland, that might be related to the timing of ES use, that is, month, day, and hour. PATIENTS AND METHODS: The medical records of all patients in whom craniofacial fractures or dental injuries caused by ES use were diagnosed at Turku University Hospital, Turku, Finland, in 2019 were reviewed. The occurrence and characteristics of injuries, with special reference to time of the accident, intoxication, hospital stay, and additional injuries sustained were analyzed. RESULTS: A total of 23 patients were identified for this analysis. The mean age was 30 years, and most patients (n = 16) were men. Four patients had not used helmets, whereas for 19, there was no mention whatsoever about helmet use. Of the patients, 21 were intoxicated and 18 had a blood alcohol content greater than 0.1%. A great majority of the accidents occurred in the nighttime (n = 17) and during weekends (n = 19). Most injuries (n = 15) occurred between September and November. We observed craniofacial fractures in 15 patients and dental injuries in 14; brain injuries occurred in 5 patients, and multiple chest injuries occurred in 1. All patients with dental injuries and 9 of the 15 patients with craniofacial fractures required interventions. An average of 3 days of hospitalization was required for 14 patients. CONCLUSIONS: Injuries associated with ESs result from driving under the heavy influence of alcohol and occur mostly during weekend nights without helmet use.

Polyomaviruses detectable in head and neck carcinomas.

Polyomaviruses (PyV) independent or jointly with human papillomavirus (HPV), might have a role in head and neck carcinomas (HNSCC). We analyzed the prevalence and viral DNA loads of SV40, JCV and BKV with quantitative PCR (qPCR) and all 13 HPyVs with a novel Multiplex method in 82 HNSCC samples with known HPV status and disease-specific survival (DSS) and 24 HNSCC cell lines. JCV was the most prevalent PyV present in 37% of HNSCC and the most prevalent sites were lip (80%), larynx (67%) and oral cavity (59%). JCV viral load was highest in larynx but variation was wide (152514 mean copies/µg DNA, SD± 304820). BKV was found only in one oral carcinoma with low viral load. SV40 was detected in 60% lip and 20.7% oral carcinomas with low copy numbers (6.6- 23.7 copies/µg DNA). Altogether, 86% of JCV-positive samples were co-infected with HPV (p=0.001), with no impact on DSS. Agreement between qPCR and Multiplex methods was substantial (Cohen's kappa= 0.659). Multiplex method detected additional HPyV in five samples. JCV was found in 9/24 HNSCC cell lines, all deriving from oral cavity. Our data provide evidence that JCV might have a role in HNSCC as independent virus or co-factor of HPV.

17ß-estradiol and progesterone effect on human papillomavirus 16 positive cells grown as spheroid co-cultures.

Human papillomavirus (HPV) is the key epidemiologic factor of cervical cancer, but additional cofactors are mandatory. Estrogen has been considered as one of those. Here, the aim was to study the effects of steroid hormones on HPV16 E6-E7, estradiol receptors ERα and ERß, and progesterone receptor (PR) in HPV16-positive cervical carcinoma cell lines SiHa and CaSki grown as epithelial and fibroblast spheroid co-cultures. The spheroid co-cultures were exposured to 17ß-estradiol or progesterone from day 7 onwards. mRNA levels of HPV16 E6-E7, ERα, ERß and PR normalized against GAPDH were analyzed with quantitative reverse transcription-qPCR (RT-qPCR). 17ß-estradiol and progesterone decreased HPV16 E6-E7 mRNA expression in CaSki and increased in SiHA co-cultures. In CaSki co-cultures, ERß expression was blocked after 17ß-estradiol exposure while in SiHa cells it slightly increased ERß expression. PR expression was seen only in CaSki spheroids and it vanished after exposure to steroid hormones. Fibroblasts expressed all three hormone receptors as monolayers but ERß expression decreased and ERα and PR vanished after co-culturing. Cell culturing platform changes both oncogene and hormone receptor expression in HPV16 positive cervical cancer cell lines. This needs to be considered when in vitro results are extrapolated to in vivo situations.

Epstein-Barr virus (EBV)-encoded small RNAs (EBERs) associated with poor prognosis of head and neck carcinomas.

BACKGROUND: Epstein-Barr virus (EBV) is the main cause of nasopharyngeal carcinoma (NPC), also found in other head and neck carcinomas (HNSCCs) where its role remains controversial. RESULTS: EBV was found in 80% and 21% of the samples with PCR and ISH (in cancer cells), respectively. Eight of ISH-positive samples were not NPCs. EBER-RNA detection in carcinoma cells was associated with worse prognosis, whether or not NPCs were included. HPV/EBV and HSV/HPV coinfections associated with a shorter survival. LMP-1 expression, positive in 51% of samples did not correlate with the disease outcome. MATERIALS AND METHODS: We analyzed EBV in 73 HNSCC samples with a known HPV and HSV-1 status, using in situ hybridization (ISH) and immunohistochemistry (IHC) for EBV-early transcripts (EBER) and LMP-1 protein, respectively. EBV-DNA was detected with a Luminex-based method. The results were correlated with HPV-status and disease outcome. CONCLUSIONS: EBV is transcriptionally active in NPC cells but also in a subgroup of other HNSCCs.

HSV-1 Infection Modulates the Radioresponse of a HPV16-positive Head and Neck Cancer Cell Line.

BACKGROUND: The combined effects of Human papillomavirus (HPV) and Herpes simplex type 1 (HSV-1) infections and their effects on cancer cell radioresistance are unexplored. MATERIALS AND METHODS: An HPV16-positive hypopharyngeal carcinoma cell line (UD-SCC-2) was infected with wt-HSV-1 at low multiplicity of infection (MOI) and irradiated with 2 Gy at 24 h postinfection. Viability assays and quantitative reverse-transcriptase PCR for HPV16 E6, E7, nuclear factor kappa B1, B-cell CLL/lymphoma 2 (BCL2), and caspases 3, 8 and 9 at 24, and 72 h, as well as immunocytochemistry for BCL2, caspase 3, cyclin E, mouse double minute 2 homolog (MDM2), HSV-1 and Ki-67 were performed at 144 h postirradiation. RESULTS: At 144 h, cell viability was significantly lowered by irradiation only in uninfected cells. Infection combined with irradiation resulted in increased expression of E6, E7, BCL2 and NF-κB1 at 144 h. Simultaneously, E6 and E7 were down-regulated in non-irradiated infected cells. Irradiation and infection with 0.00001 MOI separately up-regulated caspase 3 but infection with 0.0001 MOI halved its expression in irradiated cells. CONCLUSION: HSV-1 infection modulates radioresistance of HPV16-positive hypopharyngeal carcinoma cells.

Extracellular calcium regulates keratinocyte proliferation and HPV 16 E6 RNA expression in vitro.

Human papillomaviruses (HPV) are known to immortalize oral keratinocytes in vitro, but the underlying mechanisms causing the following resistance to differentiation remain unclear. We investigated the effect of extracellular calcium on the proliferation of HPV16-positive keratinocytes and on the mRNA expression of the viral E6-oncogene. HPV16-positive hypopharyngeal carcinoma cells (UD-SCC-2), spontaneously immortalized- (HMK) and HPV16 E6/E7-immortalized human gingival keratinocytes (IHGK) were grown for 3, 6 and 9 days in Keratinocyte Serum-free Medium with calcium concentrations ranging from 0 mM to 6 mM. Calcium concentrations up to 0.09 mM increased cellular proliferation, which decreased at higher concentrations. A shift of calcium concentration from 0 to 4 mM increased E6 expression in UD-SCC-2 cells 2.4-fold by day 9. Simultaneously, E2 expression increased. The most significant upregulation of E6 and E2 expressions was observed at day 9, grown in high-calcium media and the increase in E6 expression coincided with an increase in involucrin expression, likely indicating cell differentiation. Despite this, HPV-positive cells continued to proliferate even at high-calcium media in contrast to HPV-negative cells. Overexpression of E6 mRNA may be an important feature of HPV16-positive cells to resist the natural calcium gradient in differentiating keratinocytes allowing cell proliferation.

The combined effects of irradiation and herpes simplex virus type 1 infection on an immortal gingival cell line.

BACKGROUND: Oral mucosa is frequently exposed to Herpes simplex virus type 1 (HSV-1) infection and irradiation due to dental radiography. During radiotherapy for oral cancer, the surrounding clinically normal tissues are also irradiated. This prompted us to study the effects of HSV-1 infection and irradiation on viability and apoptosis of oral epithelial cells. METHODS: Immortal gingival keratinocyte (HMK) cells were infected with HSV-1 at a low multiplicity of infection (MOI) and irradiated with 2 Gy 24 hours post infection. The cells were then harvested at 24, 72 and 144 hours post irradiation for viability assays and qRT-PCR analyses for the apoptosis-related genes caspases 3, 8, and 9, bcl-2, NFκB1, and viral gene VP16. Mann-Whitney U-test was used for statistical calculations. RESULTS: Irradiation improved the cell viability at 144 hours post irradiation (P = 0.05), which was further improved by HSV-1 infection at MOI of 0.00001 (P = 0.05). Simultaneously, the combined effects of infection at MOI of 0.0001 and irradiation resulted in upregulation in NFκB1 (P = 0.05). The combined effects of irradiation and HSV infection also significantly downregulated the expression of caspases 3, 8, and 9 at 144 hours (P = 0.05) whereas caspase 3 and 8 significantly upregulated in non-irradiated, HSV-infected cells as compared to uninfected controls (P = 0.05). Infection with 0.0001 MOI downregulated bcl-2 in non-irradiated cells but was upregulated by 27% after irradiation when compared to non-irradiated infected cells (P = 0.05). Irradiation had no effect on HSV-1 shedding or HSV gene expression at 144 hours. CONCLUSIONS: HSV-1 infection may improve the viability of immortal cells after irradiation. The effect might be related to inhibition of apoptosis.