Salivary Biomarkers for Oral Squamous Cell Carcinoma Diagnosis and Follow-Up: Current Status and Perspectives

Oral cancer is the sixth most common cancer type in the world, and 90% of it is represented by oral squamous cell carcinoma (OSCC). Despite progress in preventive and therapeutic strategies, delay in OSCC diagnosis remains one of the major causes of high morbidity and mortality; indeed the majority of OSCC has been lately identified in the advanced clinical stage (i.e., III or IV). Moreover, after primary treatment, recurrences and/or metastases are found in more than half of the patients (80% of cases within the first 2 years) and the 5-year survival rate is still lower than 50%, resulting in a serious issue for public health. Currently, histological investigation represents the “gold standard” of OSCC diagnosis; however, recent studies have evaluated the potential use of non-invasive methods, such as “liquid biopsy,” for the detection of diagnostic and prognostic biomarkers in body fluids of oral cancer patients. Saliva is a biofluid containing factors such as cytokines, DNA and RNA molecules, circulating and tissue- derived cells, and extracellular vesicles (EVs) that may be used as biomarkers; their analysis may give us useful information to do early diagnosis of OSCC and improve the prognosis. Therefore, the aim of this review is reporting the most recent data on saliva biomarker detection in saliva liquid biopsy from oral cancer patients, with particular attention to circulating tumor DNA (ctDNA), EVs, and microRNAs (miRNAs). Our results highlight that saliva liquid biopsy has several promising clinical uses in OSCC management; it is painless, accessible, and low cost and represents a very helpful source of diagnostic and prognostic biomarker detection. Even if standardized protocols for isolation, characterization, and evaluation are needed, recent data suggest that saliva may be successfully included in future clinical diagnostic processes, with a considerable impact on early treatment strategies and a favorable outcome

Painful oral aphthous-like lesions in patient with kidney cancer after target therapy and bisphosphonate administration: a case report of adverse drug reaction.

Aim. Tyrosine kinase inhibitors (TKIs) targeting tu- mor angiogenesis and mammalian target of rapamycin inhibitors (mTOR) are indicated for the management of several cancer types, as for renal cell carcinoma (RCC). Oral ulcerations are reported as common adverse drug reactions of mTOR inhibitors and are currently classified as mTOR inhibitor associated stomatitis (mIAS). Interestingly, these lesions appear as aphthous-like stoma- titis rather than the mucositis seen with chemotherapy agent. Case report. A 49 years old male patient underwent to the left radical nephrectomy in May 2014 for clear RCC. From July to October 2014 he was treated with Pazopanib, a tyrosine kinase inhibitor. In December 2014 the patient started the treatment with Zoledronic acid and Everolimus, an amino-bisphosphonates and an mTOR inhibitor, respectively. Everolimus administration was suspended on the 1st of January 2015 and resumed on the 4th of February. In February 2015, the patient referred to our department for acute pain of mouth floor and tongue; the onset of these symptoms was subse- quent to mTOR therapy. This pain compromised his oral functions (chewing, swallowing, phonetic) and quality of life. Intraoral examination showed aphthous-like lesions on both borders of the tongue and on the right side of the mouth floor. Local antiseptic (0.2% chlorhexidine rinse, twice daily for 1 week), 0.050 g clobetasol propionate cream (twice a day for 4 week, and one times a day for the following 4 weeks) and a wound-healing promoter (Mucosamin Spray®, twice a day for 2 weeks) were administered. Since the oncologist decided to not discontinue the target therapy, the patient continued local therapy until the end of the treatment with everolimus. After two weeks from the first visit, a complete healing of the oral mucosa was observed and the patient complained no pain. Conclusion. This case report confirms the recent view that target therapy with everolimus may induce the onset of aphthous-like stomatitis as adverse drug reaction. Therefore, diagnostic algorithms for stomatitis should include a careful drug history, emphasizing the focus also on oral adverse effects the new target cancer therapies

Osteonecrosis of the jaw after long-term oral bisphosphonates, followed by short-term denosumab treatment for osteoporosis: a case report

Bisphosphonates and denosumab are antiresoptive agents and are mainly used for management of metastatic bone cancer, osteoporosis and other diseases. Bisphosphonates (BP) can reduce skeletal related events (SRE) by 30–50%1; denosumab (D) has been found even more effective than BP2. BP and D have been both associated to osteonecrosis of the jaw (ONJ). We report a case of an osteoporotic woman (62 yrs), complaining maxillary intense pain after a recent tooth molar extraction, observed in July 2013 at our centre. She mentioned previous treatments with monthly ibandronate (Bonviva ® 150 mg) per os (from January 2003 to April 2010), risedronate (35 mg weekly, from May 2010 to May 2012) and two administrations (in August 2012 and in January 2013) of denosumab (Prolia ®, 60 mg sc every 6 months). Of note, she also reported a previous incisor extraction that was performed in July 2012 (before denosumab) without ONJ onset. No further systemic or local risk factors were referred. Intraorally, bone exposure of right emimaxilla was present; osteolysis area was observed in in CT scans. According to Bedogni et al.3, the ONJ case was classified as stage II B. Medical therapy (ampicillin/sulbactam im 2 times/die, metronidazole per os 3 times/die, chlorhexidine 0.2% mouth rinses) was administered. One week later, the patient was asymptomatic but within the same stage (IIA); she was referred to Oral and Maxillofacial surgery for surgical management

Association of oral lichen planus with thyroid disease in a Finnish population: A retrospective case-control study: "A different finding from a Mediterranean area".

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