The prognostic significance of histological features in oral squamous cell carcinoma

Background:  Different factors predict nodal metastasis, recurrence and survival in oral cancer. The aim was to assess the prognostic value of histological features related to the primary tumour.
Methods:  A total of 144 patients surgically treated at Odense University Hospital for oral cancer between 1999 and 2004 were included in the study. Postoperative radiation therapy was given in case of close and involved margins or high TNM stages (UICC 1997). Median follow-up time was 38 months. All surgical resections were reviewed and 22 histological characteristics were assessed.
Results:  The predominant sites were floor of mouth (FOM, 39%) and lateral tongue (35%). Fifty-nine per cent had UICC97 stage I–II disease. Five-year cause-specific survival was observed in 65%. Nodal involvement at diagnosis was observed in 36% which was significantly related to grade, neural and vascular invasion; surgical margins and increasing tumour depth. A cut-off value of 2 mm (4 mm for FOM) separated patients without and with nodal metastasis at the time of diagnosis. However, on multivariate analysis, neck disease was only associated with tumour depth and grade. Cox analysis of local recurrence in the oral cavity over time showed that tumour diameter and surgical margins were significant predictors while cause-specific survival was related to diameter, depth of invasion, surgical margins and extracapsular spread (ECS).
Conclusions:  Tumour depth and grade were strong prognostic factors for nodal metastasis, independently of other histological features. Tumour diameter and margins independently predict local recurrences in the oral cavity as well as cause-specific survival. Nodal involvement and ECS were associated with adverse prognosis.     

Micrometastasis in oral/oropharyngeal squamous cell carcinoma: incidence, histopathological features and clinical implications.

The prognostic importance of accurate pathological staging of oral cancer patients with established lymph node metastases is well known. The present study sought to determine the incidence and clinical significance of minimal neck disease (only micrometastases) and to evaluate clinical features of the primary tumour in relation to the pathological metastatic status. Surgical resection specimens from 178 patients with oral/oropharyngeal squamous cell carcinoma were assessed by routine techniques. Micrometastases were defined as intranodal deposits measuring in total no more than 3 mm at any level of sectioning. Fourteen patients (8%) had only micrometastases and 72 (40%) had established nodal metastases. Patients with only micrometastases were younger than those with established metastases, but there were no differences in T site, T stage or sex. The outcome (2-6 years postsurgery) of patients with only micrometastases was similar to those without cervical node metastases. Hence, the main short-term significance of micrometastases seems to be in relation to clinical staging and elective management of the NO neck.     

18例侵犯颈动脉的复发性口腔、口咽鳞状细胞癌的挽救性手术治疗效果评价

目的：评估晚期口腔及口咽鳞状细胞癌（squamous cell carcinoma,简称鳞癌）的挽救性手术及颈动脉处理的效果。方法：对18例侵犯颈总动脉的复发晚期口腔鳞癌及口咽鳞癌的患者行挽救性手术治疗,包括复发灶扩大切除术、颈总动脉结扎术、颈总动脉重建术、颈总动脉解剖术、颈总动脉包裹术,并用复合组织皮瓣修复组织缺损。结果：1例患者术后暂时性偏瘫,2例患者受区创口开裂,2例患者颈动脉爆裂,1例颈总动脉重建患者术后发生颈动脉栓塞。随访5~42个月,12例无复发,2例带瘤生存,4例死于局部复发或远处转移。结论：挽救性手术可有效治疗侵犯颈总动脉的复发晚期口腔鳞癌和口咽鳞癌。根据术前评估处理受肿瘤累及的颈动脉,术式包括颈总动脉结扎术、颈总动脉重建术、颈总动脉解剖术、颈总动脉包裹术。     

口腔癌及口咽癌病理诊断规范

口腔癌及口咽癌是口腔颂面部最常见的恶性肿瘤。规范化的口腔癌及口咽癌病理诊断报告不仅应提供给临床准确的病理诊断,还应包括与患者预后评估、治疗策略选择相关的信息。由中华口腔医学会口腔病理学专业委员会牵头组织成立专家组,对口腔癌及口咽癌病理标本固定、取材及报告内容等进行研讨与规范,形成《口腔癌及口咽癌病理诊断规范》。此规范涵盖了近年来在口腔癌和口咽癌临床病理方面的一些重要变化,如口腔癌肿瘤T分期应考虑肿瘤侵袭深度、肿瘤N分期应考虑有无淋巴结外扩展、口咽癌中新亚型人乳头状瘤病毒相关性鳞状细胞癌等。希望通过本规范的制定,提高我国口腔癌及口咽癌病理报告质量,为临床治疗及预后评估提供依据。     

口腔癌及口咽癌病理诊断规范

口腔癌及口咽癌是口腔颌面部最常见的恶性肿瘤。规范化的口腔癌及口咽癌病理诊断报告不仅应提供给临床准确的病理诊断,还应包括与患者预后评估、治疗策略选择相关的信息。由中华口腔医学会口腔病理学专业委员会牵头组织成立专家组,对口腔癌及口咽癌病理标本固定、取材及报告内容等进行研讨与规范,形成《口腔癌及口咽癌病理诊断规范》。此规范涵盖了近年来在口腔癌和口咽癌临床病理方面的一些重要变化,如口腔癌肿瘤T分期应考虑肿瘤侵袭深度、肿瘤N分期应考虑有无淋巴结外扩展、口咽癌中新亚型人乳头状瘤病毒相关性鳞状细胞癌等。希望通过本规范的制定,提高我国口腔癌及口咽癌病理报告质量,为临床治疗及预后评估提供依据。     

CD44 as prognostic factor in oral and oropharyngeal squamous cell carcinoma

This retrospective case control study was conducted to assess the prognostic value of some patient-, tumor-, treatment-related variables, and to correlate markers of primary tumor with survival and cervical metastases. Twenty-five patients with histologically proven squamous cell carcinoma of the oral cavity and oropharynx were analyzed. Patients were never treated before and had a minimum follow-up review of 45 months.Results show that T-stage is the most important clinical prognostic parameter. Regarding immunohistochemical markers (Ki67 and CD44), only CD44 seems to be significantly correlated with prognosis but this value showed a multicollinear effect with N upon survival. Decreased expression of CD44 correlates with a decreased survival, although increased CD44 expression was consistent with a longer survival. Therefore, it was assessed that a loss of cell adhesion, related to decreased expression of CD44, may be determinant of survival in these patients.     

Treatment delay in early-stage oral squamous cell carcinoma and its relation to survival

The aim of this study was to investigate the impact of a prolonged treatment delay on survival in patients with primary oral squamous cell carcinoma. The investigators hypothesized that treatment delay affects survival, supposing a poor outcome in patients with prolonged treatment initiation. In addition, a critical treatment delay should be defined.Inclusion criteria were a histopathological diagnosis of primary squamous cell carcinoma of the oral cavity and a surgery-based treatment of the tumor. Patients with a history of previously diagnosed malignancies and patients with distant metastasis at the time of diagnosis were excluded from this protocol. Common clinical and histopathological data were assessed retrospectively. Treatment delay was analyzed for the interval between initial presentation and the date of surgery.A total of 484 patients could be included. Considering early-stage patients, the risk of death increases by 1.8% for each day that the treatment delay is prolonged if all other characteristics do not change (p = 0.0035). In patients with advanced disease, a prolonged treatment delay does not affect the risk of death (p = 0.9134). In terms of progression-free survival, treatment delay tends to be associated with a higher risk of recurrence in early-stage disease, but without being statistically significant (p = 0.0718). For patients with early-stage disease, a treatment delay of 20 days is critical regarding overall survival (p = 0.011). For patients with advanced-stage disease, no significant differences have been observed.As patients with early-stage oral squamous cell carcinoma profit from early treatment initiation, we suggest an acceptable maximum treatment delay of no more than 20 days in the surgical management of these patients.     

Use of Lugol's iodine in the resection of oral and oropharyngeal squamous cell carcinoma

We evaluated the use of Lugol's iodine in achieving surgical margins free from dysplasia, carcinoma in situ, and invasive carcinoma by an observational study of two series of 50 consecutive patients having resection of oral and oropharyngeal squamous cell carcinoma (SCC) between November 2004 and March 2007.     

P16蛋白在口咽癌和口腔癌中的表达及临床意义

目的:分析口咽癌和口腔癌中P16蛋白表达情况及临床意义.方法:采用免疫组织化学染色法检测70例口咽癌和60例口腔癌中P16蛋白的表达情况,分析其与患者临床病理学指标的相关性及临床意义.结果:口咽癌中P16蛋白的阳性率为22.9％(16/70),与P16阴性组相比,患者的年龄、吸烟、病理分化、N分期和TNM临床分期具有统计学意义(P＜0.05);口腔癌中P16蛋白的阳性率为8.3％ (5/60),与P16阴性组相比,病理分化和TNM临床分期有统计学意义(P＜0.05).结论:口咽癌中P16蛋白阳性率明显高于口腔癌,HPV感染是口咽癌和口腔癌不可忽视的诱发因素.     

Granisetron reduces clinical and histological response to intra-arterial neoadjuvant chemotherapy in oral squamous cell carcinoma

Intra-arterial neoadjuvant chemotherapy (TPP) with pirarubicin, cisplatin and peplomycin produced strong primary effects on oral squamous cell carcinoma, using metoclopramide (MCA) as an anti-emetic. After clinical application of granisetron (GRN), the clinical responses to TPP observed previously were weakened. In this paper, the influence of GRN on TPP is discussed. Sixty-three cases were evaluated with regard to the primary effects of TPP and anti-emetics. GRN was used in 42 cases of the GRN group, and MCA in 21 cases of non-GRN group. The clinical response rate (complete response, CR or partial response, PR) was 95.2% in the non-GRN group, and 76.2% in the GRN group. The rate of CR in the non-GRN group was 47.6%, whereas it was 9.5% in the GRN group. The histological effects in the GRN group were significantly lower (P<0.05) than those of non-GRN group. Concerning the relationship between the clinical responses and the histological responses, 4 of the 18 CR+PR cases (22.2%) in the GRN group showed good histological responses, compared with 6 of the 14 CR+PR cases (42.9%) showing in the non-GRN group. The histological responses in the GRN group were significantly lower (P<0.05) than in the non-GRN group. Our data indicate that GRN reduces the clinical and histological responses of chemotherapy.     

Relevance of level IIb neck dissection in oral squamous cell carcinoma

Background

The purpose of this study was to determine the prevalence of level IIb metastasis in patients with oral squamous cell carcinomas (OSCCs).

Material and Methods

A prospective analysis of 56 patients with OSCC who underwent surgical treatment of the primary lesion with simultaneous neck dissection was performed. During neck dissection, level IIb lymph nodes were separately removed and processed. Neck dissection was bilateral in 26 patients (46%) and unilateral in 30 patients (54%).

Results

The mean number of nodes found in the level IIb specimens was 4.7 (range: 0-8 nodes). The prevalence of metastasis at level IIb was 0% in pN0 necks and 3.4% in pN+ necks, with an overall prevalence of 1.8%. A significant association between metastasis to level IIb and type of neck dissection was observed. There were no isolated metastases to level IIb without the involvement of other nodes in the remaining neck specimen. Four regional recurrences were observed during follow-up.

Conclusions

Based on our findings, we suggest that dissection of the level IIb region in patients with OSCC may be required only in patients with multilevel neck metastasis or if level IIa metastasis is found intraoperatively. Key words: Oral squamous cell carcinoma, neck dissection, level IIb, metastasis, spinal accessory nerve.     

Management of the N0 neck in oral squamous cell carcinoma

Oral squamous cell carcinoma (SCC) has an unpredictable capacity to metastasize to the neck, an event that dramatically worsens prognosis. Metastasis occurs even in earlier stages when no neck lymph node involvement is clinically detectable (N0). Management of the N0 neck, namely when and how to electively treat, has been debated extensively. This article presents the controversies surrounding management of the N0 neck, and the benefits and pitfalls of different approaches used in evaluation and treatment. As current methods of assessing the risk for occult metastasis are insufficiently accurate and prone to underestimation of actual risk, and because selective neck dissection (SND) is an effective treatment and has minimal long-term detriment to quality of life, the authors believe that all patients who have oral SCC, excluding lip SCC, should be prescribed elective treatment of the neck lymphatics. However, this opinion remains controversial. Because of the morbidity of radiation therapy and because treatment of the primary tumor is surgical, elective neck dissection is the preferred treatment. In deciding the extent of the neck dissection, several retrospective studies and one randomized clinical trial have shown SND of levels I through III to be highly efficacious.     

Risk factors in oral and oropharyngeal squamous cell carcinoma: a population-based case-control study in southern Sweden

In the year 2002, about 275,000 inhabitants around the world developed oral cancer and over half of them will die of their disease within 5 years. Oral and oropharyngeal squamous cell carcinoma (OOSCC) accounts for about 1% of all cancers in Sweden - which is low compared to the incidence on the Indian subcontinent and in other parts of Asia, where it is one of the most common forms of cancer. The incidence in Sweden is increasing, however. The study comprised 80% (132/165) of all consecutive cases living in the Southern Healthcare Region, born in Sweden and without previous cancer diagnosis (except skin cancer), who were diagnosed with OOSCC during the period September 2000 to January 2004. Using the Swedish Population Register, 396 cancer-free controls were identified and matched by age, gender and county. Of these individuals, 320 (81%) agreed to take part in the study. Cases and controls were subjected to a standardised interview, identical oral examinations including panoramic radiographs, and cell sampling for human papillomavirus (HPV) analysis. In total 128 patients with planned curative treatment were followed for a median time of 22 months (range 0 - 36). The aims were to assess different potential risk factors in OOSCC such as oral hygiene, dental status, oral mucosal lesions, alcohol and tobacco use, virus infection, and some related to lifestyle. A further aim was to assess the influence of these factors on recurrence or occurrence of a new second primary tumour (SPT) of squamous cell carcinoma. In multivariate analysis average oral hygiene (OR 2.0; 95% CI 1.1-3.6) and poor oral hygiene (OR 5.3; 95% CI 2.5-11.3), more than 5 defective teeth (OR 3.1; 95% CI 1.2-8.2) and more than 20 teeth missing (OR 3.4; 95% CI 1.4-8.5), as well as defective or malfunctioning complete dentures (OR 3.8; 95 % CI 1.3-11.4) were identified as significant risk factors for development of OOSCC. Regular dental care reduced the risk of OOSCC (OR 0.4; 95% CI 0.2-0.6). The cases reported a higher consumption of alcohol than the controls. More than 350 g of alcohol per week (OR 2.6; 95% CI 1.3-5.4) and 11-20 cigarettes per day (OR 2.4; 95% CI 1.3-4.1) were dose-dependent risk factors. The results showed a tendency for women to have a greater risk (OR 1.8) than men at any given level of tobacco consumption. There was no increased risk of OOSCC among users of Swedish moist snuff. There was a significant relationship between high-risk human papillomavirus (HPV) infection and OOSCC (OR 63; 95% CI 14-280). Forty-seven of the cases (36%) were high-risk HPV infected and 7 (5.3%) were low-risk HPV infected in the specimens collected from the oral cavity. The corresponding figures for the controls were 3 (0.94%) and 13 (4.1%), respectively. The high-risk HPV types found in the oral cavity were the same types as observed in cervical cancer. Tumour stage was associated with both higher relative rate (RR) of recurrence or second primary tumour (SPT) of squamous cell carcinoma, and death in intercurrent diseases (DICD), defined as death before the occurrence of recurrence or SPT. High-risk HPV infected patients had an almost threefold increased RR of recurrence/SPT, but seemingly a lower RR of DICD compared to high-risk negative cases. Patients with tonsillar carcinoma had a significantly higher cause-specific RR of recurrence/SPT (RR 2.06; CI 0.99 - 4.28) compared to patients with OSCC of other sites. High alcohol consumption was associated with a high RR of recurrence/SPT, but not with DICD. There was no increased RR of recurrence/SPT related to smoking, but an association between smoking and DICD. In conclusion, the results in this study confirm that both smoking tobacco and alcohol consumption are risk factors for OOSCC. The use of Swedish moist snuff had no effect on the risk. Independent risk factors identified are poor oral hygiene, inadequate dental status and malfunctioning complete dentures. Regular dental check-ups are a preventive factor. Among other possible risk factors studied, high-risk HPV infection appears to be the strongest. High-risk HPV infection increases the cause-specific RR of recurrence or SPT. Tumour stage influences the rate of recurrence/SPT.     

Second primary tumours in oropharyngeal squamous cell carcinoma

Improved diagnostic techniques and more effective treatment concepts have resulted in a growing number of patients with oropharyngeal cancer diagnosed with second primary tumours. In order to evaluate the relative number of patients with second primary tumours and to estimate the efficacy of diagnostic procedures, a retrospective evaluation of 981 patients with oropharyngeal cancer, who were treated during 20 years in one single medical centre, was performed. In total, 9.2% of the patients were affected by secondary cancer, 1.5% from tertiary cancer and 0.2% from quartary cancer. Of the multiple cancers, 27.8% occurred synchronously and 72.2% metachronously. If the index tumour was located at the oral floor or the pharynx, the risk of second primary tumours was enhanced; if the index tumour was located at the lips or the tongue, the risk was reduced. The 5-year survival of all examined patients was 34.1%; the survival of patients with multiple cancers was 62.3% at the diagnosis of the index tumour and dropped to 30.5% at the diagnosis of an additional malignancy. Of the second primary tumours, 23.2% were diagnosed by panendoscopy. We conclude that among patients with oropharyngeal cancer, the presence of second primary tumours always has to be considered and that panendoscopy is a valuable tool for their diagnosis.     

Histopathologic risk factors in oral and oropharyngeal squamous cell carcinoma variants: An update with special reference to HPV-related carcinomas

Accurate identification of the microscopic risk factors of oral and oropharyngeal (OP) squamous cell carcinomas (SCC) and their morphologic variants is of at most importance, as these generally determine treatment modalities, prognosis and overall patient outcome. The great majority of oral and oropharyngeal squamous cell carcinomas are microscopically described as kerartinizing squamous cell carcinoma (KSCC). They bear certain resemblance to keratinizing stratified squamous epithelium. Tobacco habits and excessive consumption of alcoholic beverages have been considered to be the main etiologic agents in these carcinomas. The tumors occurred in older patients more commonly affected the oral tongue and floor of the mouth with well established morphologic risk factors including tumor grade, pattern of invasion and perineural involvement. Within the last 30 years however, the advent and expanding prevalence of high risk human papillomavirus (HPV) as an important etiologic agent for head and neck squamous cell carcinoma, particularly in the OP, has resulted in a significant change in the established morphologic criteria for risk assessment. The majority of HPV relate carcinomas of the OP are nonkeratinizing squamous cell carcinoma (NKSCC). These tumors are found to be more responsive to treatment with a favorable patient outcome and good prognosis. Consequently, alterations in treatment protocols aimed at de-escalation are currently being evaluated. More recently, other morphologic variants that are HPV positive are reported with increasing frequency in the OP and other head and neck sites. As a result, several clinical and pathologic questions have emerged. Importantly, whether the virus is biologically active in these tumors and involved in their pathogenesis, and second, what are the clinical implications with regard to patient management and outcome in the HPV-related variants. Examples of HPV-related squamous cell carcinoma variants that will be addressed here are: basaloid squamous cell carcinoma (BSCC), undifferentiated carcinoma (UCa), papillary squamous carcinoma (PSCC) and small cell carcinoma. Some studies have suggested favorable prognosis in some variants, analogous to that of the (NKSCC), while others showed poorer outcome. So far the number of studies on this subject is limited and the number of cases evaluated in each investigation is few. Because of that, it is prudent at this stage, not to alter management protocols as a result of identification of HPV in these variants and to await additional information Key words:Histopathologic risk-factors, oral cavity, oropharynx, squamous cell carcinoma variants, keratinizing squamous cell carcinoma, nonkeratinizing squamous cell carcinoma, HPV, basaloid squamous cell carcinoma, undifferentiated carcinoma, papillary squamous cell carcinoma, small cell carcinoma.