Advances of spatial omics in the individualized diagnosis and treatment of head and neck cancer / 临床耳鼻咽喉头颈外科杂志

Spatialomics is another research hotspot of biotechnology after single-cell sequencing technology, which can make up for the defect that single-cell sequencing technology can not obtain cell spatial distribution information. Spatialomics mainly studies the relative position of cells in tissue samples to reveal the effect of cell spatial distribution on diseases. In recent years, spatialomics has made new progress in the pathogenesis, target exploration, drug development and many other aspects of head and neck tumors. This paper summarizes the latest progress of spatialomics in the diagnosis and treatment of head and neck cancer.

Efficacy evaluation of transaxillary non-inflatable endoscopic surgery and open neck surgery in the treatment of PTC: a single center report of 342 cases / 临床耳鼻咽喉头颈外科杂志

Objective:To compare the clinical effect of transaxillary non-inflatable endoscopic surgery and traditional open thyroid surgery in the treatment of PTC. Methods:A retrospective analysis was performed on 342 patients with PTC treated in the Otorhinolaryngology Department of Qilu Hospital of Shandong University from December 2020 to December 2022. There were 73 males and 269 females, aged 16-72 years, who underwent unilateral non-inflatable transaxillary endoscopic thyroid surgery（endoscopic group） and unilateral traditional open thyroid surgery（open group）. There were 108 patients in the endoscopic group and 234 in the open group. Results:The endoscopic group was lower in age（37.1±9.4 vs 43.5±11.2） years and BMI（23.4±3.4 vs 25.7±3.8 ）kg/m² than that in the open group, and the difference was statistically significant（t was 5.53, 5.67 respectively, P<0.01）. There was no significant difference in hospitalization days between the two groups（P>0.05）. The logarithmic curve of the operation time showed a smooth downward trend, and the overall operation time of the endoscopic group was relatively consistent. There was no significant difference in intraoperative blood loss between the endoscopic group（13.3±3.2） mL and the open group（14.7±6.3） mL（P>0.05）, but the operation time（130.1±37.9） min was longer than that in the open group（57.4±13.7） min, and the difference was statistically significant（t=19.40, P<0.01）. There was no significant difference in complications such as temporary recurrent laryngeal nerve injury within 3 days after operation between the two groups（P>0.05）. The aesthetic satisfaction score of the surgical incision and the incision concealment effect score in the endoscopic group were higher than those in the open group, and the difference was statistically significant（P<0.05）. Conclusion:Compared with traditional open thyroidectomy, transaxillary non-inflatable endoscopic thyroidectomy has more advantages in the concealment and aesthetics of postoperative incision. Although the former has longer operation time and more drainage, it is still a safe and feasible surgical method with good postoperative clinical effect.

Treatment options for advanced laryngeal carcinoma / 中华耳鼻咽喉头颈外科杂志

Laryngeal cancer is one of the most common malignancies in the head and neck. With the development in clinical research of multimodality therapy for recent years, the treatment strategies for laryngeal cancer, especially for advanced cases, have changed significantly. The management for laryngeal cancer needs the adequate assessments of the primary tumor and the general condition of patient, the comprehensive application of multiple treatment modalities including surgery, radiation, chemotherapy and biotherapy, and the design of individualized regimens. The goal is to eradicate the tumor completely with maximal reconstruction and preservation of laryngeal functions, and to improve patient′s quality of life without reduction in survival rate.

Surgical treatment in 184 patients with supraglottic carcinoma at a single institute / 中华耳鼻咽喉头颈外科杂志

Objective@#To summarize clinical experience in surgical treatment of supraglottic carcinoma and reconstructive techniques.@*Methods@#Medical files of 184 patients (173 men, 11 women) were collected and retrospectively analyzed, who underwent surgeries between January 2008 and December 2012 at Qilu Hospital of Shandong University. Among them, T1, T2, T3 and T4 staging tumors accounted respectively for 14.1% (26/184), 41.9%(77/184), 31.5%(58/184) and 12.5%(23/184). Cervical metastasis was histologically identified in 86 cases (98 for N0, 31 for N1 and 55 for N2). Advanced cases (56 cases at stage Ⅲ and 67 at stage Ⅳ), early cases (22 at stage Ⅰ and 39 at stage Ⅱ) accounted respectively for 66.8% and 33.2%. Supraglottic horizontal laryngectomy or total laryngectomy was performed to allow for tumor excision without compromising margins and the tongue flap or sternohyoidmyofascial flap was subsequently used for repairing the defect after removal of tumor. Survival rates were analyzed by the Kaplan-Meier method.@*Results@#Patients receiving conservation laryngeal surgery accounted for 75.5% (139/184). The 3-year and 5-year survival rates for all cases were 84.2% and 70.7%, respectively. Log-rank test demonstrated that cervical lymph node metastasis, primary tumor staging and clinical TNM staging were significantly associated with prognoses of patients (P=0.003, 0.010, 0.035). Dysphagia was not observed in any case and speech function was maintained in petients with partial laryngectomy.@*Conclusion@#Adequate pre-operative evaluation, individualized treatment, and comprehensive application of flaps for repair are critical to precise tumor excision and reconstruction of laryngeal functions.

Comprehensive treatment of 335 patients with pyriform sinus carcinoma by surgery via the paraglottic space approach / 中华耳鼻咽喉头颈外科杂志

Objective@#To report the experience in comprehensive surgical treatment of pyriform sinus carcinoma via the paraglottic space approach.@*Methods@#Three hundred and thirty-five cases with pyriform sinus carcinoma (according to UICC 2012 criteria, stage Ⅰ, 12 cases; Ⅱ, 36; Ⅲ, 79; Ⅳ, 208; T1, 26; T2, 139; T3, 121; T4, 49; cN0, 83; cN1, 61; cN2a-b, 118; cN2c, 71; cN3, 2) treated between 2006 and 2013 were retrospectively reviewed. There were 323 males and 12 females. Age aged from 36 to 80 years old with a median of 60 years old. There was no case with distant metastasis. All patients received modified neck dissection, including unilateral in 240 patients and bilateral in 95 patients. Pharyngoesophageal defects were reconstructed with directly suture in 246 cases, pectoralis major musculocutaneous flaps in 74 cases, and laryngotracheal flaps in 15 cases. Three hundred and nineteen patients received postoperative radiotherapy (55-65 Gy).@*Results@#The overall 3 and 5 year survival rates were 68.6% (230/335) and 52.1%(139/267), respectively. The cervical lymph node metastases were found in 265 (79.1%) patients. Pathologic findings showed that all patients had squamous cell carcinoma. Laryngeal functions (voice, respiration and deglutition) were completely restored in 277 (82.7%) patients.@*Conclusions@#The oncological efficacy of surgery via the paraglottic space approach is sure for pyriform sinus carcinoma, especially suitable for the early and medium-term lesions. The function of the larynx can retain after surgery, with the decreased incidences of cough and pharynx fistula.

The Expression and Relationship of CD68-Tumor-Associated Macrophages and Microvascular Density With the Prognosis of Patients With Laryngeal Squamous Cell Carcinoma

OBJECTIVES: We sought to identify the expression of CD68-tumor-associated macrophages (TAMs) and CD34-microvascular density (MVD) in laryngeal squamous cell carcinoma (LSCC), to study the relationship with clinical pathological parameters and to determine whether their expression is predictive of disease. METHODS: Pathologically confirmed 45 LSCC tissue and 20 peritumoral non-tumor tissue were examined. Immunohistochemical studies were used to detect the expression of CD68-TAMs and CD34-MVD. RESULTS: The positive expression rate of CD68 in LSCC tissue was 82% (37/45), which was higher than the 10% (2/20) expression rate of the peritumoral tissue (P<0.05). The CD34-MVD positive expression rate in the LSCC tissue was 26.5±6.4, which obviously higher than 12.2±4.0 expression rate of the peritumoral tissue (P<0.05). The positive expression rates of both CD68 and CD34-MVD were higher in the lymph node metastasis (LNM) positive group than in the LNM negative group. The expression of CD68 had positive correlation with CD34-MVD. The 5-year disease-free survival rate in the group with the low CD68 expression was significantly higher than that in the group with high CD68 expression (76% vs. 42%, respectively). CONCLUSION: The high expression of CD68-TAMs in LSCC and its positive correlation with CD34-MVD illustrates that both play an important role in promoting the metastasis and angiogenesis of this cancer. Their expression was also positively correlated with the prognoses of these patients, suggesting that they could be used as important prognostic markers for LSCC.

Surgical treatment of differentiated thyroid carcinoma with laryngeal or tracheal invasion / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To analyze the clinical characters, surgical treatments and prognosis of differentiated thyroid carcinoma (DTC) with laryngeal or tracheal invasion.@*METHOD@#Forty-six cases including 33 papillary and 13 follicular were retrospectively reviewed. Thirty-four cases with tracheal invasion received conservative resection (17), window resection (11) and sleeve resection (6). One case with subglottic invasion was performed subglottic partial laryngectomy. Eleven cases with trachea-laryngeal invasion received total laryngectomy(4), 3 shave technique and 4 preservative laryngectomy.@*RESULT@#Complications included infections and hypocalcaemia, 15 patients got permanent fistula. 5-year survival rate in cases of tracheal shave resection was 88.2%, while 63.6% in those of window resection and 83.3% in those of sleeve resection. Survival rate within 5 years of patients received preservative laryngectomy was 62. 5%. Conclusion: With meticulous preoperative examination and positive surgical treatment, both survival rate and quality of life could be improved in patients of DTC with laryngeal or tracheal invasion.

Endoscopic surgery for maxillary sinus inverted papilloma / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To evaluate the effect of endoscopic surgery for maxillary sinus inverted papilloma.</p><p><b>METHODS</b>From 2000 to 2011, 50 patients with maxillary sinus inverted papilloma were treated with intranasal endoscopic surgery or combined approach. Among them, 39 cases were primary and 11 cases were recurrent, which included 17 patients with Krouse stage IIand 33 cases with Krouse stage III. Different surgical approaches were selected according to the range and positions of the lesions. One case with severe atypical hyperplasia received postoperative radiotherapy.</p><p><b>RESULTS</b>All cases were followed up for 3-14 years, 7 cases recurred. All occurrence within 2 years after operation. Malignant change and death was found in 1 case. After operation, epiphora occurred in 2 cases, maxillary sinus labiogingival groove fistula occurred in 2 cases, facial numbness occurred in 4 cases and incision hemorrhage occurred in 1 case. All the complications were cured after appropriate treatment.</p><p><b>CONCLUSIONS</b>Naso-endoscopic surgery or combined approach is a safe, effective and microinvasive treatment for patients with maxillary sinus inverted papilloma. Accurate selection of suitable approach according to the range and positions of the lesions and correct management of the base of the tumor are critical to the success of the operation.</p>

Clinical analysis of 91 cases of primary parapharyngeal space tumors / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To summarize and analyze the clinical features, diagnosis methods, surgical approaches and treatment outcomes of patients with primary parapharyngeal space tumors.</p><p><b>METHODS</b>A retrospective review of 91 cases with primary parapharyngeal space tumors treated from January 1999 to December 2011 was performed. All patients underwent preoperative enhanced CT scan and postoperative histopathologic examination. Intraoperative frozen section biopsies were performed in 36 of 91 cases. The surgical approaches included trans-cervical approach in 73 cases, trans-parotid approach in 5 cases, trans-oral approach in 5 cases, and mandibulotomy in 8 cases.</p><p><b>RESULTS</b>The postoperative pathological diagnoses consisted of 29 variants, including 20 for benign tumors and 9 for malignant tumors. Of the 80 cases with benign tumors, 6 cases were lost to follow-up and 74 cases were followed up for 31-84 months with no recurrence. Eleven cases with malignant tumor were followed up for 8-51 months (median 29 months), of them 7 cases died and 1 case was lost to follow-up. The post-operative complications included Horner syndrome in 3 cases, hoarseness in 2 cases, hypoglossal nerve palsy in 1 case, accessory nerve palsy in 1 case, upper airway obstruction in 1 case, and internal carotid artery cavernous sinus fistula in 1 case.</p><p><b>CONCLUSIONS</b>Parapharyngeal space tumors are rare, with atypical clinical manifestation, and have pathological types of diversification. CT or MRI is helpful to evaluate the tumor size, location and possible sources, and to make operation scheme. Surgery is the first choice for parapharyngeal space tumors. Trans-cervical approach can be applied to most tumors. Parapharyngeal benign tumors have good prognosis, but malignant tumors have poor prognosis.</p>

Study of expression and significance of DSCR1 gene in laryngopharynx cancer and peri-cancerous tissues / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To study the expressions of DSCR1 gene in laryngopharynx cancer and peri-cancerous tissues, to understand the relationship between its expression and tumor clinical features, to discussed the influence of DSCR1 gene on the biological behaviours of laryngopharynx squamous cell carcinoma.@*METHOD@#Immunohistochemical p-V9000 method,used rabbit DSCR1 antibody DCT3, detected the expressions of DSCR1 gene protein in laryngopharynx cancer and peri-cancerous tissues, between them and clinical data were statistically analyzed.@*RESULT@#Positive rates of DSCR1 gene expression in the tumor tissues was 94.9%, normal tissues was 35.9%, there was a statistically significant (t = 23.69, P < 0.01); There was significant difference of DSCR1 gene expressions in different pathological degree and TNM staging (P < 0.05). There was no significant difference in different age, gender, site, growth mode, lymph node metastasis and smoking history.@*CONCLUSION@#DSCR1 gene has an important role in the occurrence and development process of laryngopharynx squamous cell carcinoma, and can influence the biological behavior of tumors.

Determination of isoguanosine in Semen Crotonis Tiglii by high-performance liquid chromatography / 中西医结合学报

To develop a high-performance liquid chromatographic method for the determination of isoguanosine in Semen Crotonis Tiglii.

Mutational analysis of virus specific amino acids in the fusion active domain of paramyxovirus fusion protein / 中华微生物学和免疫学杂志

Objective To identify the effects of virus specific amino acids in the fusion active domains of paramyxovirus fusion proteins on the specific membrane fusion. Methods Site-directed mutagenesis was used to obtain mutants in the identified fusion active domains of Newcastle disease virus (NDV) fusion protein (F) and human parainfluenza virus (hPIV) fusion protein (F). All the mutant F genes were co-expressed with their homol-ogous or heterogenous hemagglutinin-neuraminidase (HN) genes in eukaryocytes. The fusion functions of mutants were assayed by Giemsa staining and reporter gene method. The expression efficiencies of mutants were assayed by fluorescence-activated cell sorter (FACS). Results In the NDV F mutants, N150D-L152D had 46.31% fusion activity of wide type. The fusion activities of N257D-N258D-Q259E, G271D-N272D and Q279E-Q281E almost disappeared, and they had only 1.25%, 3.14% and 2.23% of fusion activities, respectively, compared with wide type. N296D-N297D had 97.68% fusion activity of wide type. In the hPIV F mutants, D143A-E145A had 32.63% fusion activity of wide type. The fusion activity of E223Q-K224A almost disappeared, and it had only 1.91% fusion activity of wide type. K263A-R265A, D268A-D270A and R475A-R476A had 14.63%, 19.52% and 28.95% of fusion activities respectively compared with wild type. The analysis of FACS indicated that proteins of NDV F N257D-N258D-Q259E, G271D-N272D, Q279E-Q281E and hPIV F E223Q-K224A were not expressed on the cell surface, while proteins of the rest mutants were expressed nearly as the same as the wide types. Con-clusion As to NDV F, the amino acids of N257, N258, Q259, G271, N272, Q279 and Q281 were significant to the specific membrane fusion, and N150 and L152 were also important, but N296 and N297 were not. For hPIV F, the amino acids of E223 and K224 were significant to the specific membrane fusion, and D143, E145, K263, 11265, D268, D270, R475 and R476 were also important.

The expression and relationship of vascular cell adhesion molecule-1 and P-selectin and microvessel density in hypopharyngeal carcinoma / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To investigate the expression and significance of vascular cell adhesion molecule-1 (VCAM-1) and P-selectin in hypopharyngeal carcinoma, and explore the relationship of VCAM-1, P-selectin and microvessel density (MVD).@*METHOD@#Expression of VCAM-1 and P-selectin were detected by immunohistochemistry staining in 40 specimens of hypopharyngeal carcinoma and 10 specimens of normal mucosa of oral pharynx. MVD was assessed based on the expression of CD34.@*RESULT@#VCAM-1 and P-selectin were detected in 26 out of 40 (65%) and 29 out of 40 (72.5%) respectively in hypopharyngeal carcinoma, but none that in normal mucosa (P<0.01). MVD in hypopharyngeal carcinoma was higher than that in normal mucosa and it was related to lymph node metastasis. MVD level was significantly higher in VCAM-1 and P-selectin-positive specimens than in negative ones (P<0.01), which also positively correlated with the expression of VCAM-1 and P-selectin (P<0.01). The expression of P-selectin positively correlated with VCAM-1 in hypopharyngeal carcinoma specimens with lymph node metastasis.@*CONCLUSION@#The higher expression of VCAM-1 and P-selectin play key roles in the invasion and metastasis of hypopharyngeal carcinoma and were correlated with vascularization.

Mutation and abnormal expression of FHIT gene in hypopharyngeal carcinoma / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To analyze the mutation and abnormal expression of the FHIT gene in human hypopharyngeal carcinoma.@*METHOD@#Matched normal and cancerous tissues from 24 patients with hypopharyngeal squamous cell carcinoma were obtained immediately after surgery. Total RNA was extracted, the FHIT gene was detected by nested RT-PCR and DNA sequencing technology.@*RESULT@#Normal sized FHIT transcript was detected in 23 of the 24 cases of normal matched tissues. Aberrant FHIT transcripts were found in 9/24 (37.5%) cases in hypopharyngeal carcinoma. Aberrant FHIT transcripts rate of well-differentiated, moderately differentiated and poorly differentiated squamous cell carcinoma, was 28.6% (2/7), 50.0% (4/8) and 33.3% (3/9), respectively. There the carcinoma with FHIT aberrant transcripts was neither corresponding to histological grade (P>0.05) nor to lymphatic metastasis. The sequence analyses of the two aberrant cDNAs revealed absence of exon 8 and exon 7-9. All initial deletion were in conjunction of exons.@*CONCLUSION@#High deletion rate of the FHIT gene in Chinese hypopharyngeal squamous cell carcinoma suggested the FHIT gene, a candidate tumor suppressor gene at 3p14.2, plays an important role in the tumor carcinogenesis, development and progression of the tumor, and thus may become a new prognostic marker in hypopharyngeal carcinoma.

Perioperative treatment of functional endoscopic sinus surgery in elderly patients / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To study the characteristics of perioperative treatment of functional endoscopic nasal sinus surgery in elderly patients.@*METHOD@#Data of 186 patients above 60 years old with chronic sinusitis were retrospectively analyzed.@*RESULT@#After being received systematics and personal individuality treatment, the rates of curing were 72.5%, the rates of improving were 23.6% and the rates of efficiency were 96%.@*CONCLUSION@#The treatment of endoscopic sinus surgery is reliable and safe for elderly patients.

Expressions of cyclin D1 and p16 in hypopharyngeal squamous cell carcinoma and their clinical significance / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To study the expressions of Cyclin D1 and p16 proteins in hypopharyngeal squamous cell carcinoma and their clinical significance.@*METHOD@#Immunohistochemical technology (P-V) was applied to detect the expression of Cyclin D1 and p16 in 36 cases of hypopharyngeal squamous cell carcinoma and 10 cases of normal epithelium.@*RESULT@#(1) The expression of cyclin D1 in the tumorous cell was significantly higher than that in normal epithelium (P 0.05); (3) There was correlation between the expression of Cyclin D1 and the expression of p16 (r(s) = -0.420, P < 0.05).@*CONCLUSION@#The over-expression of Cyclin D1 and the under-expression of p16 may play a significant role in the occurrence incidence and development of hypopharyngeal squamous cell carcinoma, and may be important indicators for cervical lymph node metastases.

Clinical analysis and prognosis of stomal recurrence after laryngectomy / 中国耳鼻咽喉头颈外科

OBJECTIVE To investigate the causes of stomal recurrence after laryngectomy and the possibility of surgical management.METHODS The clinical data of 13 cases of stomal recurrence were analyzed retrospectively.RESULTS In 13 cases of stomal recurrence after laryngectomy,the survival period of 9 cases treated surgically was longer than that of 4 cases untreated or palliative treatment.CONCLUSION The overall prognosis of stomal recurrence after laryngectomy is poor.A proper surgical treatment in some cases will prolong the patient's lifetime obviously and improve his quality of life.

Reconstruction of oropharyngeal defects after resection of tonsillar cancer / 中国耳鼻咽喉头颈外科

OBJECTIVE To study the methods and curative effects of reconstruction of oropharyngeal defects after resection of tonsillar cancer. METHODS Nineteen patients with tonsillar cancer underwent operation. The choice of surgical procedure was decided on the size of the lesions. The tumor was resected through the hyoid approach and mandibular swing approach. Surgical defects were repaired immediately with tongue flap, temporalis myofascial flap, pectoralis major myocutaneous flap. RESULTS The functions of respiration, chewing, deglutition, and speech were restored satisfied in all patients. Partial necrosis of the pectoralis major myocutaneous flap occurred in one patient, and mild difficulty of open mouth in 3 patients after repaired with temporalis myofascial flap. CONCLUSION Choosing what is optimum from multiple feasible surgical methods is prerequisite for better oropharyngeal function and quality of life in patients with tonsillar cancer.

Surgical management of supraglottic laryngeal carcinoma in 182 patients with special emphasis on functional preservation / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the surgical methods and evaluate the long-term result of laryngectomy in patients with supraglottic laryngeal cancer.</p><p><b>METHODS</b>182 patients with supraglottic laryngeal carcinoma underwent operation from 1979 to 1999, with stage I 11, stage II 45, stage III 49 and stage IV 77 lesions. The choice of surgical procedure was decided with the disease condition of the larynx. The surgical procedures proposed by TD Wang were adhered to as: minor partial laryngectomy 36, major partial laryngectomy 85, subtotal partial laryngectomy with laryngoplasty 22 and total laryngectomy 39.</p><p><b>RESULTS</b>The ultimate rate of larynx preservation was 78.6% (143/182) with 69.8% (88/126) in stage III and IV diseases. The decannulation rate was 81.8% in cases with preservation of laryngeal function. The overall 3- and 5-year survival rates were 82.9% and 67.3%, with 76.88% and 57.4% in the advanced (stage III and IV) cases who survived with preserved laryngeal function. They were 82.5% and 67.0% in similar advanced cases who were treated by total laryngectomy. The difference in the survival rates between these two groups was not statistically significant.</p><p><b>CONCLUSION</b>It is suggested that preservation of the laryngeal function be possible for advanced supraglottic laryngeal carcinoma without compromising the remote survival rate. To improve the rate of larynx preservation, one should follow the surgical methods suggested.</p>

Relationship between polymorphism of N-acetyltransferase 2 and genetic susceptibility to laryngeal carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the relationship between polymorphism of N-acetyltransferase (NAT2) gene and genetic susceptibility to laryngeal carcinoma.</p><p><b>METHODS</b>A case-control study on 62 laryngeal carcinoma patients and 56 controls was conducted. NAT2 alleles were differentiated by polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) methods using originally created PCR primers and genomic DNA extracted from peripheral white blood cells. Genetic risk for NAT2 genotype was analyzed by smoking index (SI, cigarettes smoked per day x years of smoking).</p><p><b>RESULTS</b>The frequency of NAT2 slow genotype was 80.6% in patients with laryngeal carcinoma and 60.7% in the controls, the difference of which was statistically significant (chi(2) = 5.70, P = 0.017). The odds ratios were 2.70 (95% CI 1.19 approximately 6.11). Among the individuals with NAT2 slow genotype at high level of cigarette smoking, there was a significantly higher risk of 5.64 (95% CI 1.77 approximately 17.92), while those at low level were considered the reference group (OR 1.38, 95% CI 0.42 approximately 4.52).</p><p><b>CONCLUSION</b>NAT2 slow genotype increases the risk of susceptibility to laryngeal carcinoma. The combined effect of NAT2 slow genotype and exposure to smoking is observed during the development of laryngeal cancer.</p>