Cultural Beliefs on Cleft lip and/or Cleft Palate and Their Implications on Management: A Systematic Review.

OBJECTIVE: This article examines and summarizes the published epidemiological literature on cross-cultural variations. Particular emphasis was put on addressing cross-cultural beliefs on the causes, management, and attitude toward cleft lip and/or cleft palate. A healthcare provider's awareness of these cross-cultural attitudes and beliefs is vital for promoting effective collaboration with patients' families and ensuring a favorable medical outcome. DESIGN: Systematic review. SETTING: Not applicable. PARTICIPANTS: Patients with cleft lip and/or cleft palate, their families, their communities, and healthcare providers. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Not applicable. RESULTS: All relevant and eligible studies were identified using PubMed and Google Scholar databases. The cultural belief was categorized and measured using Murdock's Theories of Illness. The study was reported in compliance with PRISMA guidelines. The quality of the selected studies was evaluated in accordance with the Critical Appraisal Skills Programme criteria (CASP). Fourteen articles covering thirteen countries on four continents met the inclusion criteria. In diverse communities, cleft lip and/or cleft palate was attributed to natural (infection, medication, improper diet, smoke, or radiation) or supernatural (God, eclipse, ancestral spirit, and curse) causes. Reported consequences include stigmatization, inappropriate treatments, leaving patients untreated, and infanticide. CONCLUSION: Cultural beliefs are the main cause of misconceptions surrounding a cleft lip and/or cleft palate. There is also a need for public health care providers' intervention to educate society about the natural causes and ease of management, thereby increasing opportunities for patients substantially.

Locoregional recurrence rate and disease-specific survival following marginal vs segmental resection for oral squamous cell carcinoma with mandibular bone invasion.

BACKGROUND AND OBJECTIVES: To determine locoregional recurrence rate (LRR) and disease-specific survival (DSS) following marginal vs segmental mandibulectomy. METHODS: Included were 210 patients, who had marginal or segmental mandibulectomy between 2000 and 2017. Marginal resection was performed when complete removal of the tumor was deemed feasible on the condition that at least 1 cm bone height of the inferior border of the mandible could be preserved. Segmental resection was performed in case less than 1 cm bone height of the mandible would remain. Clinical and histopathological data were collected from medical records. LRR and DSS were computed using Kaplan-Meier analysis. Cox-regression analysis was used to identify risk factors for LRR and DSS. RESULTS: A total of 59 marginal and 151 segmental resections had been performed. There was no significant difference in 3- and 5-year LRR (P = .904) and no significant difference in 3- and 5-year DSS (P = .362) between the marginal and segmental resection group. Cox-regression analysis showed a trend for surgical margin less than equal to 1 mm, to affect LRR (P = .05) and surgical margin less than equal 1 mm, perineural invasion and lymph node metastasis to affect DSS (P < .05). CONCLUSIONS: There was no difference in outcome between the two types of mandibulectomy.

Global incidence and profile of ameloblastoma: A systematic review and meta-analysis.

OBJECTIVES: To evaluate the global incidence of ameloblastoma and to provide a profile of ameloblastoma patients. MATERIAL AND METHODS: A systematic review and meta-analysis was conducted. Searches were performed in PubMed, EMBASE, SCOPUS, and Web of Science for articles published from 1969 to 2018 for the global incidence and from 1995 to 2018 for the profile of ameloblastoma patients. RESULTS: Seven studies on the incidence rate of ameloblastoma were included in the meta-analysis. These studies only covered Europe, Africa, and Australia. The pooled incidence rate was 0.92 per million person-years (95% CI: 0.57-1.49), with significant heterogeneity between studies. Forty-two articles provided profile data of 6,446 ameloblastoma patients. Mean age was 34 years and the peak age incidence in the third decade of life. In Europe and North America, ameloblastoma mostly occurred at an older age when compared to Africa and South America. A slight male preference (53%) was found, and the mandible appeared to be the preferred site. The most common type of ameloblastoma was multicystic. The histopathologic patterns were mostly follicular and plexiform. CONCLUSIONS: This is the first study assessing the global incidence of ameloblastoma. The pooled incidence rate was determined to be 0.92 per million person-years.

Radical vs conservative treatment of intraosseous ameloblastoma: Systematic review and meta-analysis.

OBJECTIVES: The aim of the present study was to assess the outcomes of radical and conservative treatment approaches of solid/multicystic and unicystic ameloblastoma in terms of recurrence rates. MATERIAL AND METHODS: A systematic review and meta-analysis was conducted based on the PRISMA statement. Search was performed using PubMed, Embase, SCOPUS, and Web of Science for articles published from January 1969 until March 2018. Quality assessment of the selected articles was conducted using the Quality Appraisal of Case Series Studies Checklist. The meta-analysis was performed using the MedCalc program. RESULTS: The search strategy yielded 6,984 articles; 20 studies met the eligibility criteria and were included in the meta-analysis. The pooled recurrence rate of solid/multicystic ameloblastomas following radical treatment was 8%, while conservative treatment caused recurrences in 41%. For unicystic ameloblastomas, these values were 3% and 21%, respectively. The risk of recurrences in both types of ameloblastomas following radical treatment was lower than following conservative treatment. CONCLUSIONS: The present study showed statistically significant differences in recurrence favoring radical treatment for both unicystic and solid/multicystic ameloblastoma. The solid/multicystic type showed more recurrences than the unicystic type. Unfortunately, since only retrospective studies were available, the evidence is less strong as wished for.

Early and late complications in the reconstructed mandible with free fibula flaps.

BACKGROUND AND OBJECTIVES: Evaluation of mandibular reconstructions with free fibula flaps. Identification of factors associated with major recipient site complications, that is, necessitating surgical intervention under general anaesthesia. METHODS: Seventy-nine reconstructions were included. The following factors were analyzed: fixation type, number of osteotomies, site of defect (bilateral/unilateral), surgeon, sex, ASA classification, continuous smoking, pathological N-stage, age, defect size, flap ischemic time, and postoperative radiotherapy. Proportional hazards regression was used to test the effect on the time between reconstruction and intervention. RESULTS: Sixty-nine (87%) of the 79 fibula flaps were successful at the last follow-up. Forty-eight major recipient site complications occurred in 41 reconstructions. Nineteen complications required surgical intervention within six weeks and were mostly vascular problems, necessitating immediate intervention. These early complications were associated with defects crossing the midline, with an estimated relative risk of 5.3 (CI 1.1-20, P = 0.01). Twenty-nine complications required surgical intervention more than 6 weeks after the reconstruction. These late complications generally occurred after months or years, and were associated with smoking, with an estimated relative risk of 2.8 (CI 1.0-8.3, P = 0.05). CONCLUSIONS: Fibula flaps crossing the midline have a higher risk of early major recipient site complications than unilateral reconstructions. Smoking increases the risk of late complications.

Oropharyngeal squamous cell carcinomas differentially express granzyme inhibitors.

OBJECTIVES: Patients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinomas (OPSCCs) have an improved prognosis compared to HPV-negative OPSCCs. Several theories have been proposed to explain this relatively good prognosis. One hypothesis is a difference in immune response. In this study, we compared tumor-infiltrating CD3+, CD4+, CD8+ T-cells, and granzyme inhibitors (SERPINB1, SERPINB4, and SERPINB9) between HPV-positive and HPV-negative tumors and the relation with survival. METHODS: Protein expression of tumor-infiltrating lymphocytes (TILs) (CD3, CD4, and CD8) and granzyme inhibitors was analyzed in 262 OPSCCs by immunohistochemistry (IHC). Most patients (67%) received primary radiotherapy with or without chemotherapy. Cox regression analysis was carried out to compare overall survival (OS) of patients with low and high TIL infiltration and expression of granzyme inhibitors. RESULTS: HPV-positive OPSCCs were significantly more heavily infiltrated by TILs (p < 0.001) compared to HPV-negative OPSCCs. A high level of CD3+ TILs was correlated with a favorable outcome in the total cohort and in HPV-positive OPSCCs, while it reached no significance in HPV-negative OPSCCs. There was expression of all three granzyme inhibitors in OPSCCs. No differences in expression were found between HPV-positive and HPV-negative OPSCCs. Within the group of HPV-positive tumors, a high expression of SERPINB1 was associated with a significantly worse overall survival. CONCLUSION: HPV-positive OPSCCs with a low count of CD3+ TILs or high expression of SERPINB1 have a worse OS, comparable with HPV-negative OPSCCs. This suggests that the immune system plays an important role in the carcinogenesis of the virally induced oropharynx tumors.

Use of the 2-µm continuous wave thulium laser for the resection of oral squamous cell carcinomas does not impair pathological assessment.

BACKGROUND AND OBJECTIVE: Current resection modalities for oral squamous cell carcinomas (OSCC) vary from cold steel over CO2 laser to monopolar electro-surgery (MO). We compared thulium laser (TL) as a new modality with MO with regards to pathological assessment. STUDY DESIGN/MATERIALS AND METHODS: Forty-two patients who were treated for OSCC by either TL or MO were included. All resected specimens were assessed with special attention to margin interpretation and thermal damage. RESULTS: Depth of thermal damage ranged from 1.0 to 3.5 mm in the TL group compared to 1.0-4.0 mm in the MO group without interfering with the pathological assessment. The percentage of positive margin resections was three times higher in the MO group compared with the TL group. CONCLUSIONS: This study shows resections done by TL do not impair pathological assessment when compared to MO resections.

Contextualizing sociocultural beliefs about cleft, knowledge of the treatments, and factors associated with delay of treatment in Eastern Indonesia.

INTRODUCTION: Indonesia is a multicultural Asian country with a high incidence of cleft. This study contextualizes how patients' sociocultural backgrounds hinder cleft management in a diverse nation. MATERIAL AND METHODS: This study involved 202 families of cleft patients attending six tertiary care hospitals in South Sulawesi between 2021 and 2022. A mixed-methods, descriptive cross-sectional study employed semi-structured interviews and focus group discussions. Thematic content analysis was done using Murdock's causal attribution of illness. Knowledge of the treatments and surgery expectations used open coding. We held medical team focus group discussions to validate education on treatments. Cleft management education was thematically analyzed based on Indonesia's Minister of Health Decree. RESULTS: Two hundred-two families and ten medical teams participated. Thematic content analysis revealed common beliefs and factors that hinder medical treatments. The participants were 109 Buginese, 57 Makassarese, 16 Durinese, 8 Luwunese, 8 Torajanese, and 4 Mandarese. 22.3 % were unaware of causation, while 29.2 % attributed it to natural causes. About half of the interviewees believed in supernatural attribution. Even though 40 % of participants knew little about the surgery, they agreed that surgery improves appearance and speech. Medical treatments are delayed due to a lack of treatment knowledge, parents' concerns about surgical safety, and beliefs about causes. DISCUSSION: Indigenous societies in South Sulawesi believe in supernatural causes of cleft. Most had incomplete surgical treatment information. An intensive educational health program about causes, treatments, medical specialists, and treatment goals is warranted to enhance patient compliance with medical treatment, ultimately leading to improved health outcomes.

A network meta-analysis assessing the effectiveness of various radical and conservative surgical approaches regarding recurrence in treating solid/multicystic ameloblastomas.

Multiple treatment approaches have been undertaken to reduce the incidence of recurrence in solid/multicystic ameloblastoma (SMA), both conservative and radical. A network meta-analysis (NMA) was conducted to assess and compare the effectiveness of these various treatment approaches concurrently. This study was reported based on the Preferred Reporting Items for Systematic Reviews for Network Meta-Analysis (PRISMA-NMA) statement. PubMed (MEDLINE), ScienceDirect, Scopus, and Web of Science were searched until August 10, 2021. The NMA was conducted using the STATA program. Of 1153 records identified in the search, seven observational studies with 180 patients were included. Six different treatment approaches were identified. Segmental resection ranked highest for reducing the recurrence rate with the highest SUCRA score (77.7), followed by curettage with cryotherapy (66.9) and marginal resection (49.3). Network inconsistencies and publication bias appeared to be absent. According to the Confidence in Network Meta-Analysis (CINeMa) method, the evidence's certainty was low for all comparisons due to imprecision and within-study bias. In conclusion, this study is the first NMA in the field of ameloblastoma. Segmental resection seemed to be the most effective treatment approach for minimizing recurrence in SMA patients. Nevertheless, weak certainty of evidence makes that the results must be regarded with caution.

Free vascularized flaps for reconstruction of the mandible: complications, success, and dental rehabilitation.

PURPOSE: To evaluate complications and success of mandibular reconstruction with free fibula flaps, iliac crest flaps, and forearm flaps with reconstruction plates and to evaluate dental rehabilitation after these reconstructions. PATIENTS AND METHODS: Eighty-three patients with segmental mandibular defects were included. Correlation analyses were used to determine the relationship between reconstruction type and clinical parameters with recipient-site complications and success. The dental rehabilitation was evaluated in successfully reconstructed survivors. RESULTS: Multivariate analyses showed significant correlations between flap type and success (P < .0001). Of the patients, 51 (61%) were alive 2 years after the reconstruction. Mandibular reconstruction with a free forearm flap and reconstruction plate was associated with higher complication rates at the recipient site and higher failure rates compared with reconstruction with free vascularized bone flaps. Of the 32 successfully reconstructed survivors, 14 (44%) had a complete dental rehabilitation, of which 10 had dental implants and 4 did not. Only 6 (29%) of the edentulous survivors ultimately had an implant-supported prosthesis. CONCLUSIONS: Reconstruction of the mandible with a free vascularized bone flap is superior to reconstruction with a free forearm flap with a reconstruction plate. Complete dental rehabilitation was reached in fewer than half of the surviving patients.

Surgical margins in the resection of oral squamous cell carcinoma under local versus general anesthesia.

OBJECTIVES: This study analyzes the influence of the surgical setting, i.e. resection under local anesthesia versus resection under general anesthesia, on surgical margins in tumor resection of stage I and II oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: Retrospective study on tumor resections of stage I or II OSCC performed between 2014 and 2020. Potential predictors associated with surgical margins were identified. Multinomial logistic regression was used to analyze the effect of type of anesthesia on surgical margins, adjusted for potential predictors. RESULTS: In total, 109 cases were included: 54 tumor resections were performed under local anesthesia and 55 under general anesthesia. Histopathological examination showed 19 clear surgical margins, 54 close surgical margins, and 36 positive surgical margins. Compared to resection under general anesthesia, resection under local anesthesia increased the risk of close margins (adjusted OR = 6.26; 95 %CI 1.66-23.58; p = .01) and positive margins (adjusted OR = 6.81; 95 %Cl 1.70-27.27; p = .01). Tumor resection of the floor of mouth, buccal mucosa, gingiva, retromolar trigone, hard palate, and soft palate had a higher risk of close and positive margins than tumor resection of the tongue. Tumor resection of the tongue under local anesthesia was associated with an increased risk of positive margins compared to resection under general anesthesia. CONCLUSION: Tumor resection under local anesthesia of stage I and II OSCC increases the risk of close and positive surgical margins compared to tumor resection under general anesthesia.

Application and accuracy of ultrasound-guided resections of tongue cancer.

OBJECTIVES: Surgical removal of squamous cell carcinoma of the tongue (SCCT) with tumour-free margin status (≥5 mm) is essential for loco-regional control. Inadequate margins (<5 mm) often indicate adjuvant treatment, which results in increased morbidity. Ultrasound (US)-guided SCCT resection may be a useful technique to achieve more adequate resection margins compared to conventional surgery. This study evaluates the application and accuracy of this technique. METHODS: Forty patients with SCCT were included in a consecutive US cohort. During surgery, the surgeon aimed for a 10-mm echographic resection margin, while the tumour border and resection plane were captured in one image. Ex-vivo US measurements of the resection specimen determined whether there was a need for an immediate re-resection. The margin status and the administration of adjuvant treatment were compared those of with a consecutive cohort of 96 tongue cancer patients who had undergone conventional surgery. A receiver operating characteristic analysis was done to assess the optimal margin of ex-vivo US measurements to detect histopathologically inadequate margins. RESULTS: In the US cohort, the frequency of free margin status was higher than in the conventional cohort (55% vs. 16%, p < 0.001), and the frequency of positive margins status (<1 mm) was lower (5% vs. 15%, respectively, p < 0.001). Adjuvant radiotherapy was halved (10% vs. 21%), and the need for re-resection was comparable (10% vs. 9%). A cut-off value of 8 mm for ex-vivo measurements prevented histopathologically inadequate margins in 76%. CONCLUSION: US-guided SCCT resections improve margin status and reduce the frequency of adjuvant radiotherapy.

Reconstruction of the alveolar cleft: can growth factor-aided tissue engineering replace autologous bone grafting? A literature review and systematic review of results obtained with bone morphogenetic protein-2.

The alveolar cleft in patients with clefts of lip, alveolus and palate (CLAP) is usually reconstructed with an autologous bone graft. Harvesting of autologous bone grafts is associated with more or less donor site morbidity. Donor site morbidity could be eliminated if bone is fabricated by growth factor-aided tissue engineering. The objective of this review was to provide an oversight on the current state of the art in growth factor-aided tissue engineering with regard to reconstruction of the alveolar cleft in CLAP. Medline, Embase and Central databases were searched for articles on bone morphogenetic protein 2 (BMP-2), bone morphogenetic protein 7, transforming growth factor beta, platelet-derived growth factor, insulin-like growth factor, fibroblast growth factor, vascular endothelial growth factor and platelet-rich plasma for the reconstruction of the alveolar cleft in CLAP. Two-hundred ninety-one unique search results were found. Three articles met our selection criteria. These three selected articles compared BMP-2-aided bone tissue engineering with iliac crest bone grafting by clinical and radiographic examinations. Bone quantity appeared comparable between the two methods in patients treated during the stage of mixed dentition, whereas bone quantity appeared superior in the BMP-2 group in skeletally mature patients. Favourable results with BMP-2-aided bone tissue engineering have been reported for the reconstruction of the alveolar cleft in CLAP. More studies are necessary to assess the quality of bone. Advantages are shortening of the operation time, absence of donor site morbidity, shorter hospital stay and reduction of overall cost.

Oral squamous cell carcinoma involving the maxillae: Factors affecting local recurrence and the value of salvage treatment for overall survival.

OBJECTIVE: To determine factors associated with local recurrence (LR) of oral squamous cell carcinoma involving the maxillae (MSCC) and overall survival (OS) after salvage treatment. SUBJECTS AND METHODS: Retrospective study of MSCC operated between 2000 and 2015. Kaplan-Meier survival and Cox regression were used for analysis of MSCC-associated clinical and histopathological factors. RESULTS: Ninety-five patients were included. LR occurred in 24% of patients. Vascular invasion significantly increased the risk of LR (hazard ratio 4.595, P = .003). Local salvage surgery, in the area of the original tumor, significantly prolonged OS, compared to palliative treatment (P = .001) and extensive salvage surgery (P = .013). Extensive salvage surgery, requiring resection of adjacent facial structures, did not prolong OS compared to palliative treatment (P = .186). CONCLUSIONS: MSCC with vascular invasion has higher risk of LR. Salvage surgery may prolong OS in small recurrences but might have dubious value for larger recurrences infiltrating adjacent facial structures.

Nonvascularized bone grafts for segmental reconstruction of the mandible--a reappraisal.

PURPOSE: To evaluate the success rate and complications of segmental mandibular reconstructions with autogenous nonvascularized iliac crest bone grafts, and to refine treatment strategies. PATIENTS AND METHODS: Seventy-four patients with segmental mandibular defects were included. Malignant lesion, immediate reconstruction, smoking habit, radiotherapy, site of the defect, surgical approach, and method of graft fixation were analyzed as factors of influence on success. Success was defined as maintenance of bone continuity and stability, and absence of infection 1 year after reconstruction upon clinical and radiographic examination. Complications were divided into recipient and donor-site complications and classified as minor or major. The reconstruction was considered functionally complete if prosthetic rehabilitation was accomplished or if there was a sufficient remaining dentition for mastication. RESULTS: In 56 (76%) patients, the initial reconstruction was successful. Multivariate analyses showed that symphyseal involvement (SI) and intraoral approach (IA) were significantly associated with failure (P(SI) = .022, P(IA) = .038) and major recipient-site complications (P(SI) = .022, P(IA) = .038). Thirty-two (43%) patients showed complications in the first postoperative year: 27 recipient-site complications and 6 donor-site complications. Nineteen (70%) recipient-site complications were classified as major. The reconstruction was functionally complete in 48 (86%) of the 56 patients with a successful initial reconstruction. CONCLUSIONS: Nonvascularized iliac crest bone grafts for segmental reconstruction of the mandible is the method of choice on the condition that the defect is truly lateral and only an extraoral approach is used. In these cases, microvascular tissue transfer is not necessary.

Predicting individualized mortality probabilities for patients with squamous cell carcinoma of the maxilla: Novel models with clinical and histopathological predictors.

BACKGROUND: The aim of this article was to develop prediction models that calculate postoperative 2- and 5-year mortality probabilities of patients with squamous cell carcinoma of the maxilla (MSCC). METHODS: Data were collected from the medical records of patients who had been operated between 2000 and 2015 for MSCC. Potential clinical and histopathological predictors were identified. Confounding-(un)adjusted multivariate Cox and logistic regression models were computed with stepwise backward selection. Internal validation was performed to assess calibration and discriminatory ability. RESULTS: Ninety-five patients with MSCC were included. Two-year follow-up was complete, and 85 patients had 5-year follow-up. Age, neck treatment, surgical margins, bone invasion, spindle growth, and vasoinvasive growth were associated with mortality. Models were adjusted for confounding with Charlson's comorbidities index. C-indexes were .841 and .770 respectively, and .838 and .749 after bootstrapping. CONCLUSION: The MSCC-specific mortality probability can be calculated with new prediction models.

Intraoral ultrasonography to measure tumor thickness of oral cancer: A systematic review and meta-analysis.

Early oral cancer is preferably treated by surgery. Its complete removal is essential for locoregional control and disease-free survival. Inadequate resection margins require adjuvant therapy such as re-resection or (chemo)radiation, that causes extra morbidity and oral discomfort. Intraoral ultrasonography (US) is reported to be of value in determining tumor thickness. Intraoperative visualization of the tumor may facilitate the resection and ensure adequate surgical margins. Furthermore, accurate prediction of tumor thickness could help determine the treatment strategy of the clinically node-negative neck, as thickness and depth of invasion are predictors of cervical metastasis as well as prognosticators of survival. The 8th edition of the American Joint Committee on Cancer staging system for oral squamous cell carcinoma has included depth of invasion as parameter for cT-stage. The aim of this review is to analyze the accuracy of intraoral US in determining tumor thickness in oral cancer. A systematic search was conducted, and the quality of the included papers was assessed using the QUADAS-2 tool for diagnostic accuracy studies. Subsequently, a meta-analysis was performed on the available individual participant data of 240 patients. Most of the twelve included studies focused on T1-2 tongue cancer (n = 129). Meta-analysis showed a high correlation in tumor thickness within this subgroup as measured by intraoral US and histopathology (r = 0.82, p < .001), with minor overestimation of 0.5 mm on US. It is concluded that intraoral US is very accurate in determining tumor thickness in early oral tongue cancer.

Management of the clinically node negative neck in squamous cell carcinoma of the maxilla.

OBJECTIVE: The management of the clinically node negative (N0) neck in patients with squamous cell carcinoma of the maxilla (MSCC) is a matter of debate. In this retrospective cohort study the incidence of occult metastases is determined in clinically N0 MSCCs, as well as histopathological factors associated with occult metastases. PATIENTS AND METHODS: 95 patients with clinically N0 MSCCs had maxillectomy. 18 patients with elective treatment of the neck were excluded. The remaining 77 patients followed a 'watch and wait' strategy for the neck and were included in this study. The incidence of occult metastases was calculated and Cox regression analysis was used to assess the predictive and prognostic value of clinical and histopathological parameters. RESULTS: Occult metastases occurred in 14.3% (11/77) in the whole cohort and in 19.0% (11/58) in T2-T4 clinically N0 MSCC. Patients with T4 clinically N0 MSCC, showed the highest rate of occult metastases (24.1%). 45.5% of the occult metastases developed in the contralateral neck. The hazard ratio to develop occult metastasis was 5.39 (p=0.017) for perineural growth and 11.12 (p=0.003) for perivascular invasion. Salvage for cervical recurrence was poor at 40%. CONCLUSION: We recommend elective treatment of the neck or improved diagnostics to detect occult metastases in T2-T4 clinically N0 MSCC or when the biopsy specimen shows perineural growth or perivascular invasion. Since the contralateral neck was involved in 45.5% of the regional recurrences, we emphasize the importance of bilateral neck management. Improved diagnostics, like sentinel node biopsy, could possibly further reduce occult metastatic disease.

Cell-free nucleic acids in body fluids as biomarkers for the prediction and early detection of recurrent head and neck cancer: A systematic review of the literature.

Liquid biopsy is a minimally invasive detection method for molecular biomarkers in body fluids which may serve as a novel tool in management of head and neck cancer. The purpose of this systematic review is to outline the current status of liquid biopsy in head and neck squamous cell carcinoma (HNSCC) patients by systematically identifying and qualifying all published studies on the diagnostic or prognostic value of cell-free nucleic acids detection for posttreatment disease monitoring and/or disease outcome. A search was performed in PubMed, EMBASE, and Cochrane Library. Thirty articles met the inclusion criteria for further analysis. Study and patient characteristics, molecular analysis method and treatment or prognostic outcomes were extracted. Seventeen studies investigated circulating miRNAs in blood. Of these studies, 16 found statistically significant results for a total of 24 different candidate miRNAs for prognostication or treatment monitoring. The remaining studies investigated circulating tumor DNA by targeting somatic mutations, allelic imbalances, hypermethylation, or HPV-DNA. Of these studies, 2 found a statistically significant association between nucleic acid levels (tumor DNA targeted by allelic imbalances and HPV-DNA) in blood and/or saliva and prognostic outcome. One study found significantly different pre- and posttreatment levels of mitochondrial DNA in serum. Despite large differences among these studies in both design and results, individual results are promising and provide ground for more large-scale studies with standardized serial assessment of patient samples in the future.