<?xml version="1.0" encoding="UTF-8"?><!DOCTYPE article  PUBLIC "-//NLM//DTD Journal Publishing DTD v3.0 20080202//EN" "http://dtd.nlm.nih.gov/publishing/3.0/journalpublishing3.dtd"><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" dtd-version="3.0" xml:lang="en" article-type="research article"><front><journal-meta><journal-id journal-id-type="publisher-id">OJPathology</journal-id><journal-title-group><journal-title>Open Journal of Pathology</journal-title></journal-title-group><issn pub-type="epub">2164-6775</issn><publisher><publisher-name>Scientific Research Publishing</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.4236/ojpathology.2023.132008</article-id><article-id pub-id-type="publisher-id">OJPathology-122933</article-id><article-categories><subj-group subj-group-type="heading"><subject>Articles</subject></subj-group><subj-group subj-group-type="Discipline-v2"><subject>Medicine&amp;Healthcare</subject></subj-group></article-categories><title-group><article-title>
 
 
  Laryngeal Cancers at the Pathological Anatomical Laboratory (ACP) in Dakar about 215 Cases
 
</article-title></title-group><contrib-group><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Marie</surname><given-names>Joseph Dieme Ahouidi</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="corresp" rid="cor1"><sup>*</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Adama</surname><given-names>Diedhiou</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Abdou</surname><given-names>Magib Gaye</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Dibor</surname><given-names>Niang</given-names></name><xref ref-type="aff" rid="aff3"><sup>3</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Falilatou</surname><given-names>Seidou</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Ibou</surname><given-names>Thiam</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Cherif</surname><given-names>Mouhamed Moustapha Dial</given-names></name><xref ref-type="aff" rid="aff4"><sup>4</sup></xref></contrib></contrib-group><aff id="aff1"><addr-line>Anatomy and Pathological Cytology Laboratory, Fann Hospital, Dakar, Sénégal</addr-line></aff><aff id="aff4"><addr-line>Anatomy and Pathological Cytology Laboratory, Idrissa Pouye Hospital, Dakar, Sénégal</addr-line></aff><aff id="aff2"><addr-line>Anatomy and Pathological Cytology Laboratory, Aristide Le Dantec Hospital, Dakar, Sénégal</addr-line></aff><aff id="aff3"><addr-line>Anatomy and Pathological Cytology Laboratory, Gaston Berger University, St Louis, Sénégal</addr-line></aff><pub-date pub-type="epub"><day>08</day><month>02</month><year>2023</year></pub-date><volume>13</volume><issue>02</issue><fpage>79</fpage><lpage>86</lpage><history><date date-type="received"><day>1,</day>	<month>November</month>	<year>2022</year></date><date date-type="rev-recd"><day>6,</day>	<month>February</month>	<year>2023</year>	</date><date date-type="accepted"><day>9,</day>	<month>February</month>	<year>2023</year></date></history><permissions><copyright-statement>&#169; Copyright  2014 by authors and Scientific Research Publishing Inc. </copyright-statement><copyright-year>2014</copyright-year><license><license-p>This work is licensed under the Creative Commons Attribution International License (CC BY). http://creativecommons.org/licenses/by/4.0/</license-p></license></permissions><abstract><p>
 
 
  Introduction: Laryngeal cancer is the first cancer of upper aerodigestive tract. Dysphonia, dyspnea and dysphagia are evocative signs. Diagnosis is histological and squamous cell carcinoma is the most common type. The objective of our study was to discuss epidemiological and anatomo-pathological characteristics of laryngeal cancers diagnosed in different pathological anatomy and cytology (ACP) laboratories of Dakar hospitals. 
  Material and method: This was a retrospective study spanning from January 2013 to December 2018 at the pathological anatomy laboratories of Fann, Aristide Le Dantec and Idrissa Pouye hospitals. All patients with laryngeal cancer confirmed at histology were included. Data collection was based on clinical records of the patients and archives of histological reports of the pathological laboratories. Data analysis was performed under the Excel software. 
  Results: We collected 215 cases of laryngeal cancer. The average age was 58.01 years with extremes of 07 and 94 years. The male sex was predominant with 183 patients (85.12%) against 32 women (14.88%). The most noted risk factor was tobacco which affected 14 patients, or 60.87%. Three patients (13.04%) did not present any alcohol-smoking impregnation. Clinically, dysphonia was noted in 22 patients (26.51%). It was associated with dyspnea in 0.48% of cases and dysphagia in 3.61%. Laryngoscopy was performed in 62 patients or 28.83% of cases, nasofibroscopy in 6.45% of cases. Cord arythenoid fixity was noted in two patients (3.23%) and hypo-mobility in 1 patient (1.61%). The most frequent local extension was involvement of the piriform sinus with 11.29% of cases. Palpable lymphadenopathy reported in 17 patients (20.48%). Pathological examination was performed in all patients after post endoscopic biopsy in 92 patients (42.79%), and after obtaining the operative specimen in 123 cases (57.21%). The three floors affected 76 patients (35.35%). The ulcerative budding aspect most noted concerned 108 patients (60.97%). Histologically, it was a squamous cell carcinoma in 205 patients (95.34%). The most site invaded by the tumor was cricoid cartilage.T4 type was most found (45 patients or 40.90%) followed by the T3 type with 34.55%. There was no lymphadenopathy invasion (Type N0) in 74 patients (67.27%), capsular rupture was reported in five patients (6.77%), no evaluable metastasis in 110 patients (97.27%), and stage IVA predominated in 66 patients (60%). 
  Conclusion: laryngeal cancer is a reality in our contexts, however, its incidence is poorly understood in Senegal. The main risk factors remain tobacco and alcohol. Histology confirms the diagnosis. Its management is multidisciplinary and must be early.
 
</p></abstract><kwd-group><kwd>Laryngeal Cancer</kwd><kwd> Carcinoma</kwd><kwd> Dakar</kwd></kwd-group></article-meta></front><body><sec id="s1"><title>1. Introduction</title><p>Laryngeal cancers, on the rise worldwide, are dominated by squamous cell carcinoma. They represent 3.5% of malignant tumors diagnosed annually worldwide [<xref ref-type="bibr" rid="scirp.122933-ref1">1</xref>].</p><p>Incidence and mortality rates are higher in Europe and lower in Africa, but the ratio between deaths and incidence is the highest in Africa. Cigarette smoking and alcohol abuse contribute for about 90% of overall worldwide mortality for laryngeal cancer [<xref ref-type="bibr" rid="scirp.122933-ref2">2</xref>].</p><p>In most African countries, the majority of patients come to the clinic at advanced stages of the disease [<xref ref-type="bibr" rid="scirp.122933-ref3">3</xref>]. This situation causes a real problem of management especially when we know that cancers in general are more serious in sub-Saharan Africa where mortality rates are on average around 75% [<xref ref-type="bibr" rid="scirp.122933-ref4">4</xref>]. The anatomo-pathological examination confirms the diagnosis and specifies the tumor extension in the lymph node areas and neighboring organs for an adequate therapeutic choice. The objective of our study was to discuss epidemiological and anatomo-pathological characteristics of laryngeal cancers diagnosed in three ACP laboratories of Dakar.</p></sec><sec id="s2"><title>2. Material and Methods</title><p>This was a retrospective and descriptive study spanning 5 years, covering the period between January 2013 and December 2018. It was carried out using the archives and registers of histological reports from pathological anatomy and cytology laboratories (ACP) at university hospitals of Fann, Aristide Le Dantec and General Idrissa Pouye. All patients with histologically confirmed laryngeal cancer were included. A survey form was prepared for each patient with the following items: age, sex, risk factors, clinical symptoms, the seat of the tumor, the ulcerated, budding and/or infiltrating characters, the histological type of the tumor, the state of the resection margins, the different types of lymph node dissection, the number of lymph nodes as well as the neighboring organs invaded and The TNM classification were recorded.</p><p>The data collected was analysed using Excel 2010 and SPSS 20.0.</p></sec><sec id="s3"><title>3. Results</title><p>1) Prevalence</p><p>Between January 2013 and December 2018, two hundred and fifteen (215) laryngectomy specimens were collected.</p><p>2) Sex</p><p>These samples concerned 183 men who constituted 85.12% of the series and 32 women or 14.88% (<xref ref-type="fig" rid="fig1">Figure 1</xref>). The sex ratio was 5.7.</p><p>3) Age</p><p>The average age of these patients was 58.01 years, with extremes of 07 and 94 years. In men, it was 59.75 years while in women the average age was 48 years. The most affected age group regardless of gender was between 51 and 60 years old with 33.95% of the series (<xref ref-type="fig" rid="fig2">Figure 2</xref>).</p><p>4) Risk factors</p><p>The risk factors were only specified in 23 patients (10.70%). One hundred and ninety-two (192) reports did not include information on the presence or absence of risk factors. Among these 23 patients, 14 (60.87%) were chronic smokers, the quantity consumed being specified in only two patients and varying between 5 and 15 packets of years. No case of isolated alcohol poisoning had been notified. The association of smoking and alcohol was reported in 6 patients (26.09%).</p><p>5) Clinical aspects</p><p>Dysphonia was the most noted clinical sign, concerned 22 patients (26.51%) of the cohort and the association of dysphonia and dyspnea was noted in 17 patients (21.25%). Eight (8) patients (10%) of the series, had consulted for dysphagia and 14 for cervical lymphadenopathy (17.5%) (<xref ref-type="table" rid="table1">Table 1</xref>). Indirect laryngoscopy performed in 62 patients of the cohort (28.83%) had reported a lesional process in these patients.</p><p>6) Macroscopy</p><p>The tumoral lesion was purely budding in 69 patients (32.09%), infiltrative for 30 patients (13.95%) of cases, ulcerated in 4 cases (1.87%) and mixed in 112 patients (52.09%) of this cohort. In this batch of mixed lesions, one hundred and eight (108) cases of budding ulcer lesion, two (2) cases of budding and infiltrating form and 2 cases of infiltrating ulcer had been identified (<xref ref-type="table" rid="table2">Table 2</xref>). The laryngeal tumor was located on the 3 levels of the larynx in 76 patients (35.35%), on the glottic level in 35 patients (16.27%), on the glotto supraglottic level for 26 patients (12. 09%) and on the subglottic floor 15 cases (6.97%).</p><p>7) Microscopy</p><p>The histological examination was carried out on biopsy samples in 92 patients (42.79%), and on an operating specimen in 123 patients (57.21%). Keratinizing differentiated squamous cell carcinoma constituted 95.34% of the series (205 cases). The other histological types were represented by adenoid cystic carcinoma (2 cases), spindle cell carcinoma (2 cases), verrucous carcinoma (1 case) and mucosquamous cell carcinoma (1 case).</p><table-wrap id="table1" ><label><xref ref-type="table" rid="table1">Table 1</xref></label><caption><title> Distribution of clinical signs</title></caption><table><tbody><thead><tr><th align="center" valign="middle" >Clinical signs</th><th align="center" valign="middle" >Effective</th><th align="center" valign="middle" >Percentage (%)</th></tr></thead><tr><td align="center" valign="middle" >Dysphonia</td><td align="center" valign="middle" >22</td><td align="center" valign="middle" >27.5</td></tr><tr><td align="center" valign="middle" >Laryngeal dyspnea</td><td align="center" valign="middle" >5</td><td align="center" valign="middle" >6.25</td></tr><tr><td align="center" valign="middle" >Dysphagia</td><td align="center" valign="middle" >8</td><td align="center" valign="middle" >10</td></tr><tr><td align="center" valign="middle" >Dysphonia + dyspnea</td><td align="center" valign="middle" >17</td><td align="center" valign="middle" >21.25</td></tr><tr><td align="center" valign="middle" >Dysphonia + dysphagia</td><td align="center" valign="middle" >3</td><td align="center" valign="middle" >3.75</td></tr><tr><td align="center" valign="middle" >Dysphagia + Dyspnea</td><td align="center" valign="middle" >4</td><td align="center" valign="middle" >5</td></tr><tr><td align="center" valign="middle" >Dysphagia + Dyspnea + Dysphonia</td><td align="center" valign="middle" >4</td><td align="center" valign="middle" >5</td></tr><tr><td align="center" valign="middle" >Odynophagia</td><td align="center" valign="middle" >3</td><td align="center" valign="middle" >3.75</td></tr><tr><td align="center" valign="middle" >Lymph node</td><td align="center" valign="middle" >14</td><td align="center" valign="middle" >17.5</td></tr><tr><td align="center" valign="middle" >Total</td><td align="center" valign="middle" >80</td><td align="center" valign="middle" >100</td></tr></tbody></table></table-wrap><p>Squamous cell carcinoma was well differentiated in 159 patients (73.95%), moderately differentiated in 36 patients (16.74%) and poorly differentiated in 7 patients (3.26%).</p><p>The lower resection margin passed into the tumor zone in 16.66% (9 cases).</p><p>The cricoid cartilage was invaded in 53.40% (55 cases), the thyroid in 22.3% (23 cases) (<xref ref-type="fig" rid="fig3">Figure 3</xref>) (<xref ref-type="table" rid="table3">Table 3</xref>).</p><table-wrap id="table2" ><label><xref ref-type="table" rid="table2">Table 2</xref></label><caption><title> Macroscopic appearance of the laryngeal tumor</title></caption><table><tbody><thead><tr><th align="center" valign="middle" >Characters</th><th align="center" valign="middle" >Number</th><th align="center" valign="middle" >Percentage (%)</th></tr></thead><tr><td align="center" valign="middle" >Ulcer</td><td align="center" valign="middle" >4</td><td align="center" valign="middle" >1.87</td></tr><tr><td align="center" valign="middle" >Ulc&#233;ro-budding</td><td align="center" valign="middle" >108</td><td align="center" valign="middle" >50.23</td></tr><tr><td align="center" valign="middle" >Budding</td><td align="center" valign="middle" >69</td><td align="center" valign="middle" >32.09</td></tr><tr><td align="center" valign="middle" >Infiltrating</td><td align="center" valign="middle" >30</td><td align="center" valign="middle" >13.95</td></tr><tr><td align="center" valign="middle" >Ulcero-infiltrating</td><td align="center" valign="middle" >2</td><td align="center" valign="middle" >0.93</td></tr><tr><td align="center" valign="middle" >Infiltrating and budding</td><td align="center" valign="middle" >2</td><td align="center" valign="middle" >0.93</td></tr><tr><td align="center" valign="middle" >Total</td><td align="center" valign="middle" >215</td><td align="center" valign="middle" >100</td></tr></tbody></table></table-wrap><table-wrap id="table3" ><label><xref ref-type="table" rid="table3">Table 3</xref></label><caption><title> Distribution of local tumor infiltration</title></caption><table><tbody><thead><tr><th align="center" valign="middle" >Local infiltration</th><th align="center" valign="middle" >Number</th><th align="center" valign="middle" >Percentage (%)</th></tr></thead><tr><td align="center" valign="middle" >Cricoid cartilage</td><td align="center" valign="middle" >55</td><td align="center" valign="middle" >53.40</td></tr><tr><td align="center" valign="middle" >Aryt&#233;noid cartilage</td><td align="center" valign="middle" >3</td><td align="center" valign="middle" >2.91</td></tr><tr><td align="center" valign="middle" >Thyroid cartilage</td><td align="center" valign="middle" >2</td><td align="center" valign="middle" >1.94</td></tr><tr><td align="center" valign="middle" >Thyroid gland</td><td align="center" valign="middle" >23</td><td align="center" valign="middle" >22.33</td></tr><tr><td align="center" valign="middle" >Anterior commissure</td><td align="center" valign="middle" >12</td><td align="center" valign="middle" >11.65</td></tr><tr><td align="center" valign="middle" >Posterior commissure</td><td align="center" valign="middle" >5</td><td align="center" valign="middle" >4.85</td></tr><tr><td align="center" valign="middle" >Trachea</td><td align="center" valign="middle" >3</td><td align="center" valign="middle" >2.91</td></tr><tr><td align="center" valign="middle" >Total</td><td align="center" valign="middle" >103</td><td align="center" valign="middle" >100</td></tr></tbody></table></table-wrap><p>Lymph node status was studied on an average of 15 lymph nodes per case. Lymph node invasion was noted in 35 patients (31.82%) of the series and capsule rupture specified in 5 patients (6.77%).</p><p>The TNM classification was made in 110 patients (51.16%).</p><p>The T4 type occupied the first rank and concerned 45 patients (40.90%), followed by the T3 type with 38 patients (34.55%). Stages IVA and III were the most frequently diagnosed with respectively 66 patients (60%) and 37 patients (33.60%).</p></sec><sec id="s4"><title>4. Discussion</title><p>Our series included 215 cases collected over 5 years. By comparing our results with those of Mvouni Oyono et al. [<xref ref-type="bibr" rid="scirp.122933-ref5">5</xref>] (18 cases in 6 years) and Diouf et al. [<xref ref-type="bibr" rid="scirp.122933-ref6">6</xref>] (61 cases in 10 years), the prevalence of laryngeal cancers in this series shows a clear increase. Authors in Brazzaville [<xref ref-type="bibr" rid="scirp.122933-ref7">7</xref>] listed 46 patients with laryngeal cancer in a hospital cohort over ten years, which indicated a double progression compared to their 2002 series. The actual prevalence of laryngeal cancer in Senegal is poorly known due to the absence of a national cancer registry. This situation is common to some African countries where the available figures are those evaluated from hospital cases as shown by the Togolese [<xref ref-type="bibr" rid="scirp.122933-ref8">8</xref>] and Cameroonian [<xref ref-type="bibr" rid="scirp.122933-ref9">9</xref>] series. The incidence and prevalence of this cancer have increased by 12% and 24%, respectively, over the past 3 decades. Men have a more than 5-fold higher incidence (4.64 versus 0.86 per 100,000 population) [<xref ref-type="bibr" rid="scirp.122933-ref2">2</xref>]. This male predominance was also noted in our study. The mean age of the patients was 58.01 years with extremes of 07 and 94 years. It was 59.7 years for men and 48 years for women. The most represented age group was between 51 and 60 years (33.95%), regardless of gender. Ondzotto et al. found a mean age of 61 years [<xref ref-type="bibr" rid="scirp.122933-ref3">3</xref>]. The Chinese study reported that the incidence of laryngeal malignancies peaked after 65 years of age in both sexes [<xref ref-type="bibr" rid="scirp.122933-ref2">2</xref>]. The risk factors in this study had only been identified in 23 patients, (10.70%) of the cohort. Smoking was the predominant factor noted in 14 patients, while the alcohol-tobacco association concerned only 6 patients. For Amana et al., alcohol smoking predominated in laryngeal cancer [<xref ref-type="bibr" rid="scirp.122933-ref8">8</xref>]. The Cameroon series by Njimah et al. [<xref ref-type="bibr" rid="scirp.122933-ref9">9</xref>] showed alcohol (59.35%) as the most common risk factor ahead of tobacco (44.72%). Hemmaoui et al. in Morocco [<xref ref-type="bibr" rid="scirp.122933-ref10">10</xref>] had reported 90% tobacco-related poisoning. Malignant lesions of the larynx of epithelial origin are associated with tobacco and predominate in men [<xref ref-type="bibr" rid="scirp.122933-ref11">11</xref>]. Otouana D et al. had reported that for some authors, infection with the Human papilloma virus (HPV) is the risk factor to be discussed apart from alcohol and tobacco [<xref ref-type="bibr" rid="scirp.122933-ref7">7</xref>]. The main risk factors for squamous cell carcinoma, more frequent cancers of the aero-digestive tract, are alcohol consumption, tobacco and infection with Human Papilloma virus [<xref ref-type="bibr" rid="scirp.122933-ref12">12</xref>]. The small number of cases reported on the presence or absence of risk factors does not allow us to evaluate the real role of alcohol, tobacco and HPV infection in the pathogenesis of laryngeal cancers. It would also be interesting to look for other carcinogenic factors such as genetic and dietary factors.</p><p>Dysphonia, the predominant symptom in our series, concerned 26.51% of our patients (22 out of 83 patients), was associated with dyspnea in 17 patients (20.48%), with dysphagia in 3 patients (3.61% ) and dyspnea and dysphagia in 4 patients (4.82%). The most frequent mode of revelation in the Congolese cohort was represented by the association chronic dysphonia—laryngeal dyspnea [<xref ref-type="bibr" rid="scirp.122933-ref3">3</xref>], as for our series. The mixed budding ulcer character was the most frequent in our study. The pure budding type constituted 85% of the Congolese series [<xref ref-type="bibr" rid="scirp.122933-ref3">3</xref>] and Njimah et al. on a set of oto-rhinolaryngology tumors had reported 48% budding appearance [<xref ref-type="bibr" rid="scirp.122933-ref9">9</xref>]. Squamous cell carcinoma was the most frequent histological type in this series, and represented 95.34% (205/215) laryngeal cancers of the series. This result is close to that of the cohort of Ciolofan et al. who also reported 95% (462/490) squamous cell carcinoma of laryngeal cancers [<xref ref-type="bibr" rid="scirp.122933-ref13">13</xref>].</p><p>In the Congolese series [<xref ref-type="bibr" rid="scirp.122933-ref7">7</xref>], squamous cell carcinoma was the only histological type diagnosed. This histological type is the most frequent of the upper aerodigestive tract in several countries [<xref ref-type="bibr" rid="scirp.122933-ref12">12</xref>] [<xref ref-type="bibr" rid="scirp.122933-ref13">13</xref>]. The other histological types in our series were represented by carcinoma variants: adenoid cystic carcinoma (2 cases), spindle cell carcinoma (2 cases), verrucous carcinoma (1 case) and mucosquamous cell carcinoma (1 case). Ciolofan et al. [<xref ref-type="bibr" rid="scirp.122933-ref13">13</xref>] had found alongside other forms of carcinoma (6 basaloid carcinomas, 4 verrucous) other histological types such as leiomyosarcoma (1 case), chondrosarcoma (1 case), and melanoma (1 case). This series of 490 patients comprised a majority of patients diagnosed at an advanced stage (75% for stage IV and 23% for stage III) [<xref ref-type="bibr" rid="scirp.122933-ref13">13</xref>]. These findings are quite similar to those noted in our study where stage IV involved 60% of patients, stage III 33.60%. Otouana Dzon et al. in their series noted 85% of patients diagnosed at stage IV [<xref ref-type="bibr" rid="scirp.122933-ref7">7</xref>]. Laryngeal cancers are diagnosed at a late stage in our regions. This diagnostic delay will influence and make difficult the management of this scourge, which raises the need for effective radiotherapy.</p><p>Our work was limited by the lack of information especially regarding risk factors, tumor size and clinical signs. Indeed, the pathologists only see the sample and the information sheet. The latter must be well filled out in order to have all the necessary elements for an exhaustive analysis of the results.</p></sec><sec id="s5"><title>5. Conclusion</title><p>The diagnosis of laryngeal cancer is histological and it conditions the therapeutic choice. The quality of the histological report of laryngectomy specimens is linked to that of the sample sent to the laboratory. The management of laryngeal cancers requires close collaboration between clinicians, ENT surgeons, pathologists and oncologists.</p></sec><sec id="s6"><title>Conflicts of Interest</title><p>The authors declare no conflicts of interest regarding the publication of this paper.</p></sec><sec id="s7"><title>Cite this paper</title><p>Ahouidi, M.J.D., Diedhiou, A., Gaye, A.M., Niang, D., Seidou, F., Thiam, I. and Dial, C.M.M. (2023) Laryngeal Cancers at the Pathological Anatomical Laboratory (ACP) in Dakar about 215 Cases. Open Journal of Pathology, 13, 79-86. https://doi.org/10.4236/ojpathology.2023.132008</p></sec></body><back><ref-list><title>References</title><ref id="scirp.122933-ref1"><label>1</label><mixed-citation publication-type="other" xlink:type="simple">Prades, J.M. and Reyt, E. (2013) Cancer du larynx. 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