Early Diagnosis of Oral Cancer and Lesions in Fanconi Anemia Patients: A Prospective and Longitudinal Study Using Saliva and Plasma

Abstract

Fanconi anemia (FA) patients display an exacerbated risk of oral squamous cell carcinoma (OSCC) and oral potentially malignant lesions (OPMLs) at early ages. As patients have defects in their DNA repair mechanisms, standard-of-care treatments for OSCC such as radiotherapy and chemotherapy, give rise to severe toxicities. New methods for early diagnosis are urgently needed to allow for treatment in early disease stages and achieve better clinical outcomes. We conducted a prospective, longitudinal study wherein liquid biopsies from sixteen patients with no clinical diagnoses of OPML and/or OSCC were analyzed for the presence of mutations in cancer genes. The DNA from saliva and plasma were sequentially collected and deep-sequenced, and the clinical evaluation followed over a median time of approximately 2 years. In 9/16 FA patients, we detected mutations in cancer genes (mainly TP53) with minor allele frequencies (MAF) of down to 0.07%. Importantly, all patients that had mutations and clinical follow-up data after mutation detection (n = 6) developed oral precursor lesions or OSCC. The lead-time between mutation detection and tumor diagnosis ranged from 23 to 630 days. Strikingly, FA patients without mutations displayed a significantly lower risk of developing precursor lesions or OSCCs. Therefore, our diagnostic approach could help to stratify FA patients into risk groups, which would allow for closer surveillance for OSCCs or precursor lesions.

The onset and progression of oral potentially malignant disorders in Fanconi anemia patients: Highlighting early detection of oral cancer

“… Errazquin et al. 2023 16 Spain 16 11 (68.8%) NA 27 (14–46) Follow-up 24 (15–37) 6 (37.5%) 2 (12.5%) Saliva & plasma 9/16 FA patients had mutations in at least one liquid biopsy sample; all of them displayed OPMD/OSCC afterwards; 7/16 patients displayed no mutations, 6 of whom were free of OPML/OSCC. HPV, human papillomavirus; HSCT, hematopoietic stem cell transplantation; GVHD, graft-versus-host disease; NA, not available; OPMD, oral potentially malignant disorders; OSCC, oral squamous cell carcinoma.…”

“…As presented in Table 1 , there were 11 eligible papers containing 1 retrospective study, 2 case reports, 4 cross-section studies, and 4 follow-up studies involved in OPMD onset in FA patients. 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 A total of 1332 patients with FA from 7 countries (France, Brazil, Italy, United States, Netherlands, Germany, and Spain) are identified in literature. Among 1332 FA patients, 186 (14.0%) were diagnosed with OPMD.…”

“… 5 Apart from one study including 16 FA patients with oral leukoplakia from Brazil, we herein add 10 studies including 186 FA patients diagnosed with oral potentially malignant visible lesions. 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 We pool the incidence of OPMD onset in FA patients being 14.0%, which is obviously higher than overall prevalence (4.47%) of OPMD worldwide reported by systematic review and meta-analysis. 17 Further, we synthesize the rate of malignant transformation in FA patients with OPMD being 41.1%, which is also dramatically higher than overall rate (7.9%) of OPMD malignant transformation reported by systematic review and meta-analysis ( Table 1 ).…”

Quantitative Detection of Biological Nanovesicles in Drops of Saliva Using Microcantilevers

“…Saliva is arguably one of the most challenging bodily fluids to operate in given the presence of large biopolymers forming gel–liquid structures, but this can be overcome by accordingly adapting the mechanical sensing. The choice of saliva is also motivated by its potential for noninvasive and real-time diagnostics of infective and neoplastic diseases. , To illustrate the capabilities of our method, we target the model and native extracellular nanovesicles (EVs). EVs are small (30–300 nm) phospholipid-based vesicles present in most bodily fluids including blood, saliva, and urine. , They are secreted by cells into the surrounding connective matrix and are naturally used as vehicles to cargo small molecules, proteins, and nucleic acids between distant cells and throughout the body .…”

“…The choice of saliva is also motivated by its potential for noninvasive and real-time diagnostics of infective and neoplastic diseases. 14 , 15 To illustrate the capabilities of our method, we target the model and native extracellular nanovesicles (EVs). EVs are small (30–300 nm) phospholipid-based vesicles present in most bodily fluids including blood, saliva, and urine.…”