Juan P. Rodrigo

Frequent genetic and biochemical alterations of the PI 3-K/AKT/PTEN pathway in head and neck squamous cell carcinoma.

We investigated the status of the PI 3‐kinase/AKT/PTEN signaling pathway in a series of 117 head and neck squamous cell carcinomas (HNSCC) in a search for molecular alterations in genes/proteins with potential prognostic value. For this purpose, PIK3CA and AKT2 gene amplification was assessed by multiplex and Quantitative Real‐Time PCR. Protein expression of AKT, p‐AKT, p110α and PTEN was determined by Western blot. PTEN allelic loss was evaluated by microsatellite analysis. PTEN‐exon 5 was screened for point mutations by PCR‐SSCP. Homozygous deletions were determined by multiplex PCR. PIK3CA gene was amplified in 43/117 (37%) fresh tumor samples, a frequency that did not differ from that found in archival premalignant tissues: 15/38 (39%); 12/40 (30%) fresh tumors harbored AKT2 gene amplification. AKT was found activated in 6/36 (17%) fresh tumor samples, when compared to their normal tissue counterparts. Of these 6 cases, 1 showed p110α overexpression and 5 displayed PTEN protein downregulation. Neither allelic loss (found in 11/77 informative cases) nor point mutations or homozygous deletions accounted for the reduced PTEN protein expression observed in our tumor series. The histologically normal mucosa of 4 patients displayed some of the molecular alterations analyzed. Dysregulation of the PI 3‐K/AKT/PTEN pathway might contribute to early HNSCC tumorigenesis and might constitute a potential clinical target. Overall, 17/36 (47%) cases showed at least 1 of the molecular alterations studied here, which makes the PI 3‐kinase‐initiated signaling pathway one of the most frequently altered in HNSCC.

Surgical margins in head and neck cancer: a contemporary review.

Adequate resection margins are critical to the treatment decisions and prognosis of patients with head and neck squamous cell carcinoma (HNSCC). However, there are numerous controversies regarding reporting and interpretation of the status of resection margins. Fundamental issues relating to the basic definition of margin adequacy, uniform reporting standards for margins, optimal method of specimen dissection, and the role of intraoperative frozen section evaluation, all require further clarification and standardization. Future horizons for margin surveillance offer the possible use of novel methods such as “molecular margins” and contact microscopic endoscopy, However, the limitations of these approaches need to be understood. The goal of this review was to evaluate these issues to define a more rational, standardized approach for achieving resection margin adequacy for patients with HNSCC undergoing curative resection.

Annexin A1 Down-Regulation in Head and Neck Cancer Is Associated with Epithelial Differentiation Status

Annexin A1 (ANXA1) protein expression was evaluated by Western blot in a series of 32 head and neck squamous cell carcinomas (HNSCCs) in a search for molecular alterations that could serve as useful diagnostic/prognostic markers. ANXA1 down-regulation was observed in 24 cases (75%) compared with patient-matched normal epithelium. In relation to clinicopathological variables, ANXA1 down-regulation was significantly associated with advanced T stages (P = 0.029), locoregional lymph node metastases (P = 0.038), advanced disease stage (P = 0.006), hypopharyngeal localization (P = 0.038), and poor histological differentiation (P = 0.005). ANXA1 expression was also analyzed by immunohistochemistry in paraffin-embedded sections from 22 of 32 HNSCCs and 8 premalignant lesions. All dysplastic tissues showed significantly reduced ANXA1 expression compared to a strong positive signal observed in adjacent normal epithelia (except basal and suprabasal cells). A close association was observed between ANXA1 expression and the histological grade in HNSCC. Well-differentiated tumors presented a positive ANXA1 signal in highly keratinized areas whereas moderately and poorly differentiated tumors exhibited very weak or negative staining. Our findings clearly identify ANXA1 as an effective differentiation marker for the histopathological grading of HNSCCs and for the detection of epithelial dysplasia.

HUMAN PAPILLOMAVIRUS INFECTIONS IN LARYNGEAL CANCER

Although the association and clinical significance of human papillomavirus (HPV) infections with a subset of head and neck cancers, particularly for oropharyngeal carcinoma, has recently been well documented, the involvement of HPV in laryngeal cancer has been inadequately evaluated. Herein we review the currently known associations of HPV infections in diseases of the larynx and their potential for oncogenicity. Using several methods of detection, HPV DNA has been detected in benign (papillomatosis), indolent (verrucous carcinoma), and malignant (squamous cell carcinoma) lesions of the larynx. Consistent with the known oncogenic risk of HPV infections, common HPV types associated with laryngeal papillomatosis include low‐risk HPV types 6 and 11, with high‐risk HPV types 16 and 18 more commonly present in neoplastic lesions (verrucous carcinoma and squamous cell carcinoma). Although a broad range of prevalence has been noted in individual studies, approximately 25% of laryngeal squamous cell carcinomas harbor HPV infections on meta‐analysis, with common involvement of high‐risk HPV types 16 (highest frequency) and 18. Preliminary results suggest that these high‐risk HPV infections seem to be biologically relevant in laryngeal carcinogenesis, manifested as having viral DNA integration in the cancer cell genome and increased expression of the p16 protein. Despite this knowledge, the clinical significance of these infections and the implications on disease prevention and treatment are unclear and require further investigation.

Prognostic factors in paranasal sinus cancer

PURPOSE This study was designed to evaluate the influence of several different prognostic factors in determining both local recurrence rates and survival in patients treated for carcinoma of the paranasal sinuses. MATERIALS AND METHODS A retrospective study of patients treated between January, 1975 and December, 1991 was undertaken. Hospital charts were reviewed collecting demographic, clinical, and radiographic findings, which were correlated with treatment and subsequent follow-up. RESULTS Carcinoma of the paranasal sinuses was identified in 129 patients. This included 95 men and 34 women with an average of 59 years. The ethmoid sinus was primarily involved in 50 patients, the maxillary sinus and 49, the nasal sinus and 25, sphenoid sinus in three in the frontal sinus and two patients. Advanced stage (T3/T4) was diagnosed in 60% of patients at presentation. The most commonly encountered histologies were squamous-cell carcinoma and adenocarcinoma. The most accurate predictors of poor prognosis were advanced T stage and involvement of the anterior skill base. Involvement of the posterior wall of the maxillary sinus, infratemporal fossa, and erosion of the orbital wall was not associated with the worst prognosis. CONCLUSION In spite of advances in imaging technique and surgical therapy, the primary cause of death is inability to control local disease. Diagnosis at an earlier stage is associated with improved outcome.

Contemporary management of lymph node metastases from an unknown primary to the neck: I. A review of diagnostic approaches

In an era of advanced diagnostics, metastasis to cervical lymph nodes from an occult primary tumor is a rare clinical entity and accounts for approximately 3% of head and neck malignancies. Histologically, two thirds of cases are squamous cell carcinomas (SCCs), with other tissue types less common in the neck. With modern imaging and tissue examinations, a primary tumor initially undetected on physical examination is revealed in >50% of patients and the site of the index primary can be predicted with a high level of probability. In the present review, the range and limitations of diagnostic procedures are summarized and the optimal diagnostic workup is proposed. Initial preferred diagnostic procedures are a fine‐needle aspiration biopsy (FNAB) and imaging. This allows directed surgical biopsy (such as tonsillectomy), based on the preliminary findings, and prevents misinterpretation of postsurgical images. When no primary lesion is suggested after imaging and panendoscopy, and for patients without a history of smoking and alcohol abuse, molecular profiling of an FNAB sample for human papillomavirus (HPV) and/or Epstein–Barr virus (EBV) is important. Head Neck, 2013

Advances and applications of oral cancer basic research.

Cancer of the oral cavity accounts for almost 3% of cancer cases in the world. The incidence varies widely reflecting geographic differences in exposure to risk factors. The recent rise in younger age groups and females seen in many countries is of particular concern. Treatment and management of complications, locoregional recurrence and further primary tumors result in high morbidity and mortality especially when the disease is advanced stage at initial diagnosis. Progress in cancer research has provided abundant new knowledge about cellular processes and molecular biology underlying oral carcinogenesis and tumor progression. The present review attempts to summarize the current most widely-used research approaches and their application in the prevention, diagnosis, effective treatment, and improved outcome of oral cancer.

Current treatment options for recurrent nasopharyngeal cancer

Loco-regional control rate of nasopharyngeal carcinoma (NPC) has improved significantly in the past decade. However, local recurrence still represents a major cause of mortality and morbidity in advanced stages, and management of local failure remains a challenging issue in NPC. The best salvage treatment for local recurrent NPC remains to be determined. The options include brachytherapy, external radiotherapy, stereotactic radiosurgery, and nasopharyngectomy, either alone or in different combinations. In this article we will discuss the different options for salvage of locally recurrent NPC. Retreatment of locally recurrent NPC using radiotherapy, alone or in combination with other treatment modalities, as well as surgery, can result in long-term local control and survival in a substantial proportion of patients. For small-volume recurrent tumors (T1–T2) treated with external radiotherapy, brachytherapy or stereotactic radiosurgery, comparable results to those obtained with surgery have been reported. In contrast, treatment results of advanced-stage locally recurrent NPC are generally more satisfactory with surgery (with or without postoperative radiotherapy) than with reirradiation.

ONCOLOGIC OUTCOMES OF TRANSORAL LASER SURGERY OF SUPRAGLOTTIC CARCINOMA COMPARED WITH A TRANSCERVICAL APPROACH

To evaluate the oncologic effectiveness of transoral laser surgery of supraglottic cancer, we compared a group of patients treated with laser surgery, with a stage‐matched group treated with a transcervical approach.

Chemotherapy and targeted therapy in adenoid cystic carcinoma of the head and neck: a review.

Adenoid cystic carcinoma (ACC) is an uncommon tumor usually arising in the head and neck region, mainly in the salivary glands. It demonstrates an indolent prolonged course and is characterized by perineural invasion. Primary treatment of local and locoregional disease consists mainly of surgery and/or irradiation. During follow‐up these patients frequently develop local recurrences and distant metastases, especially in the lung, although long‐term survival is possible. The role of chemotherapy in ACC is limited, and studies with only a limited number of patients are performed. In this article we review the literature on chemotherapy regimens, including monotherapy and combination chemotherapy schedules, as well as the new targeted therapies.