Julia A. Woolgar

Survival following primary surgery for oral cancer

The main aims of this article are to report the overall and disease-specific survival of a consecutive series of patients presenting with oral cancer from 1992 to 2002 and to relate survival to clinical and pathological factors. The article uses population-based age-sex mortality rates in the North-West of England to highlight differences in overall and disease-specific survival. 541 patients with oral squamous cell carcinoma presented to the Regional Maxillofacial Unit from 1992 to 2002. Curative treatment favoured radical primary surgery, 10% (52) received primary radiotherapy. These patients were on average 8 years older with more advanced tumours and overall poorer survival at 5 years, 23% (SE 7%). The remainder of the results refer to 489 patients who had primary curative surgery, 40% (194) of whom received adjuvant radiotherapy. The overall survival (OS) was 56% (SE 2%) and the disease-specific survival (DSS) was 74% (SE 2%). There was a local recurrence rate of 10% (50) and the loco-regional recurrence rate was 21% (103). The second primary rate was 7% (35). Survival figures had improved over the 10-year period from 63% DSS for the first 4 years of the study (1992-1995) compared to 81% for the last 3 years (2000-2002). In stepwise Cox regression the two predictors selected for disease-specific survival were pN status and margins (both p<0.001). Age-sex mortality rates for the North-West indicate that 15.0% of the 489 primary surgery patients might have been expected to die within 5 years if they were typical of the general population and the observed difference between all causes and oral-cancer specific survival was 18.3%. These data emphasise the value of disease-specific survival as an indicator of successful treatment in a cohort that tends to be elderly, from social deprived backgrounds, with life styles and comorbidity that influence overall survival.

Evaluation of Human Papilloma Virus Diagnostic Testing in Oropharyngeal Squamous Cell Carcinoma: Sensitivity, Specificity, and Prognostic Discrimination

Purpose: Human papillomavirus-16 (HPV16) is the causative agent in a biologically distinct subset of oropharyngeal squamous cell carcinoma (OPSCC) with highly favorable prognosis. In clinical trials, HPV16 status is an essential inclusion or stratification parameter, highlighting the importance of accurate testing. Experimental Design: Fixed and fresh-frozen tissue from 108 OPSCC cases were subject to eight possible assay/assay combinations: p16 immunohistochemistry (p16 IHC); in situ hybridization for high-risk HPV (HR HPV ISH); quantitative PCR (qPCR) for both viral E6 RNA (RNA qPCR) and DNA (DNA qPCR); and combinations of the above. Results: HPV16-positive OPSCC presented in younger patients (mean 7.5 years younger, P = 0.003) who smoked less than HPV-negative patients (P = 0.007). The proportion of HPV16-positive cases increased from 15% to 57% (P = 0.001) between 1988 and 2009. A combination of p16 IHC/DNA qPCR showed acceptable sensitivity (97%) and specificity (94%) compared with the RNA qPCR “gold standard”, as well as being the best discriminator of favorable outcome (overall survival P = 0.002). p16 IHC/HR HPV ISH also had acceptable specificity (90%) but the substantial reduction in its sensitivity (88%) impacted upon its prognostic value (P = 0.02). p16 IHC, HR HPV ISH, or DNA qPCR was not sufficiently specific to recommend in clinical trials when used in isolation. Conclusions: Caution must be exercised in applying HPV16 diagnostic tests because of significant disparities in accuracy and prognostic value in previously published techniques. Clin Cancer Res; 17(19); 6262–71. ©2011 AACR.

Survival and patterns of recurrence in 200 oral cancer patients treated by radical surgery and neck dissection

The outcome of 200 patients with squamous cell carcinoma of the oral/oropharyngeal mucosa managed by primary radical surgery and simultaneous neck dissection and followed for 2.2-8.5 years is reported and related to the pathological features. Ninety-nine patients (50%) had cervical lymph node metastases including 16 (8%) with bilateral metastases. Actuarial (life tables) survival analysis showed the overall 2-year survival probability was 72%, falling to 64% at 5 years. The 5-year survival probability was 81% for patients without metastasis, 64% for patients with intranodal metastases and 21% for patients with metastases showing extracapsular spread. A total of 60 patients (30%) died of/with their cancer: 36 (18%) of local recurrence; 4 (2%) of a metachronous primary tumour; 14 (7%) of regional disease, and 6 (3%) with systemic metastases. A further 15 patients (8%) had relapsed but were clinically disease-free after additional surgery. In all, 7% of the series developed metachronous primary tumours. In addition to nodal metastasis, survival was related to the site and stage of the primary tumour, the histological grade and pattern of invasion, status of the resection margins and pathological TNM stage. For patients with lymph node metastasis, extracapsular spread was an important indicator of tumour behaviour and we recommend its use as a criterion for pathological N staging.

Cervical lymph node metastasis in oral cancer: the importance of even microscopic extracapsular spread

The prognostic significance of extracapsular spread of cervical metastases in oral cancer is still controversial. To investigate the importance of extent of extracapsular spread; the relationship between extracapsular spread and both traditional measures of metastatic disease and clinical/histological features of the primary tumour, and to determine their relative prognostic significance. The survival of 173 patients undergoing radical surgery and simultaneous neck dissection for oral/oropharyngeal squamous cell carcinoma with histologically confirmed nodal metastasis and followed for 2.2-12.3 years is reported and related to pathological features. The most predictive clinical/histopathological features were determined by Cox regression modelling. The 3-year survival probability was similar for patients with macroscopic and only microscopic extracapsular spread (33 and 36%, respectively, compared with 72% for patients with intranodal metastasis). The Cox model showed the most predictive factor was extracapsular spread followed by status of resection margins. Extracapsular spread should be incorporated into pathological staging systems. Even microscopic extracapsular spread is of critical importance and must be sought especially in small-volume metastatic disease.

Prevalence of mucosotropic human papillomaviruses in squamous-cell carcinomas of the head and neck

The prevalence of mucosotropic human papillomavirus (HPV) DNA in 63 squamous‐cell carcinomas (SCC) from different anatomic sites in the head and neck was determined by general primer‐mediated polymerase chain reaction (GP‐PCR). HPV DNA was detected in 20.6% of SCC. Additional type‐specific PCR for HPV 6, 11, 16, 18, 31 and 33 demonstrated the presence of HPV 16 alone in these carcinomas. HPV 16 was also detected in normal epithelium from the resection margins of the majority of HPV‐positive SCC. HPV status did not correlate with tumour site, whether primary or recurrent, TNM stage, metastases, degree of differentiation, smoking or alcohol history, fate or survival.

Patterns of invasion and routes of tumor entry into the mandible by oral squamous cell carcinoma.

An understanding of the patterns, spread, and routes of tumor invasion of the mandible is essential in deciding the appropriate level and extent of mandibular resection in oral squamous cell carcinoma.

A review of quality of life assessment in oral cancer

Quality of life is important in patients with oral and oropharyngeal cancer. The assessment of quality of life is complex and it is difficult to identify the studies and questionnaires previously reported that have dealt with quality of life assessment in patients with oral cancer. This article gives guidelines for choosing a questionnaire, provides a tabulated summary of 65 studies published in the English language from 1980 to 1997, and gives a brief description of 27 commonly used questionnaires. The review is of particular assistance to the clinician who is considering embarking upon quality of life research in oral cancer.

Extracapsular spread in oral squamous cell carcinoma.

Extracapsular spread (ECS) in the cervical lymph nodes represents the most significant adverse prognostic indicator in oral squamous cell carcinoma (OSCC).

Pitfalls and procedures in the histopathological diagnosis of oral and oropharyngeal squamous cell carcinoma and a review of the role of pathology in prognosis

Histopathological assessment of formalin-fixed biopsy tissue and surgical resection specimens remains the cornerstone of cancer diagnosis and pathological staging in routine clinical practice. In recent years, standard protocols for reporting head and neck cancer have been widely used and these have improved the general level of the pathological assessment. In this article, we look beyond the standard protocols and deal with potential difficulties and pitfalls in the assessment of incisional biopsy specimens, surgical resection specimens and neck dissections. We draw attention to possible shortcomings and issues requiring clarification. Emphasis is given to precise histopathological definitions, histopathological detection and differential diagnosis. The approach is a practical one--a consideration of common experiences and dilemmas faced by the reporting pathologist, and where possible, we offer guidance and practical tips. The article concludes with a brief consideration of the prognostic value of accurate histopathological staging.

The influence of the pattern of mandibular invasion on recurrence and survival in oral squamous cell carcinoma.

Controversy exists over the predictive value of the presence and pattern of tumor invasion of the mandible in oral squamous cell carcinoma (SCC). Many authors have questioned increasing the classification of small tumors to T4 on the basis of mandibular invasion alone. There are little data on the influence of the pattern of invasion on prognosis.