Patient and Tumour Characteristics of Adult Head and Neck Soft Tissue Sarcomas: A Systematic Review and Meta-Analysis.

BACKGROUND: Head and neck soft tissue sarcomas (HNSTS) constitute a rare and heterogeneous cancer entity. Management remains a challenge due to the rarity and varied biological behaviour among various subtypes. This systematic review examines the characteristics of tumours and patients with HNSTS. MATERIALS AND METHODS: A systematic literature review and meta-analysis were performed using the electronic databases PubMed and Embase. Eight eligible studies were identified, and 13 variables were extracted from each study including 5-year overall survival (OS) rate and 5-year disease-free survival (DFS) rate. RESULTS: We identified eight studies (n = 1,120 patients; 739 males (66%)) from six different countries). In total, 24 histological subtypes were found, and 20% of the sarcomas (n = 215) could not be subclassified. 607 sarcomas (57%) were <5 cm in diameter, and 945 sarcomas (84%) were grade 3. 1,059 patients (90%) underwent surgery. Estimated 5-year OS was 74% (95% CI; 0.63-0.84%) and 5-year DFS was 56% (95% CI; 38-74%). CONCLUSION: HNSTS holds a relative poor prognosis possibly explained by the heterogeneity of the disease. Treatment of HNSTS has shown to be highly diverse, underlining the importance of uniformed treatment guidelines in order to achieve improved survival outcomes.

Comparison of clinical, radiological and morphological features including the distribution of HPV E6/E7 oncogenes in resection specimens of oropharyngeal squamous cell carcinoma.

BACKGROUND: Human papillomavirus (HPV)-driven oropharyngeal squamous cell carcinoma (OPSCC) represents a distinct tumour entity in comparison to HPV-negative OPSCC. The clinical, radiological, morphological features and distribution of HPV E6/E7 mRNA were investigated in resected specimens of OPSCC. METHODS: We retrieved formalin-fixed, paraffin-embedded whole section slides from 24 p16/HPV-DNA positive and 18 p16/HPV-DNA negative primary tumours and 16 corresponding metastases in patients with early-stage OPSCC who underwent planned curative or diagnostic primary transoral robotic surgery. A detailed clinicoradiological and histopathological investigation of the tumours was performed along with detection of HPV E6/E7 mRNA by in situ hybridisation. RESULTS: HPV-driven OPSCC was characterised by non-keratinising morphology and was dominated by a cohesive invasion pattern at the leading edge of the tumour. Dysplastic zones of the squamous epithelium were strictly located in the tonsillar crypts in contrast to HPV-negative OPSCC which predominantly arised from the dysplastic surface epithelium. Thirteen HPV-driven OPSCC invaded through the tonsillar lymphoid compartment and into soft tissue, causing a stromal desmoplastic reaction. HPV mRNA was consistently but inhomogenously expressed in the entire tumour area and in the dysplastic squamous epithelium. There was no HPV expression in the adjacent normal epithelium and in the non-neoplastic tissues. CONCLUSIONS: This study enhances the current understanding of HPV-driven OPSCC. Only tumours that invade through the lymphoid compartment induce a stromal desmoplastic reaction. A consistent but inhomogenous expression of E6 and E7 mRNA was found in tumour and dysplastic areas, emphasizing that the E6/E7 oncogenes are the driving factors in HPV-driven OPSCC.

Correlation between HPV status at T and N sites of oropharyngeal squamous cell carcinomas.

OBJECTIVES: Human papilloma virus (HPV) is known to be associated with oropharyngeal squamous cell carcinomas (OPSCC) and may potentially play a vital role in tumor metastasis. The purpose of this study was to correlate HPV status of cervical lymph node metastases with their respective primary OPSCC tumor. METHODS: Formalin-fixed, paraffin-embedded (FFPE) tissue samples obtained from 34 patients with cervical lymph node metastases were analyzed with HPV 16 DNA polymerase chain reaction (PCR), p16 immunohistochemistry and HPV typing. The results were correlated with the HPV status and type found in the primary tumors of OPSCC. RESULTS: Comparing HPV DNA status with p16 we found that 21 primary tumors and lymph node metastases were HPV positive (61.8%) and seven primary tumors and lymph node metastases were HPV negative (20.6%). Six patient samples differed when correlating the primary tumor and lymph node metastasis (17.6%). CONCLUSIONS: In this study, HPV status in OPSCCs and their cervical lymph node metastases correlated in the vast majority of cases. However, HPV detection methods may have certain limitations resulting in varying degree of non-correlation. This should be taken into account when stratifying treatment in regard to HPV status.

[Human papillomavirus and oropharyngeal cancer].

The prevalence of oropharyngeal cancer is increasing in the Western world, and human papillomavirus (HPV) is believed to play a role in this development. Patients with HPV-positive oropharyngeal cancer differ significantly from patients with HPV-negative cancer. They may present solely with a small cervical metastasis and thus undergo an extensive diagnostic workup. Treatment modalities include radiotherapy often in combination with chemotherapy. However, new surgical advances are now possible. In this review we discuss the changing epidemiology, virology, symptomatology and different treatment modalities.

Primary transoral robotic surgery with concurrent neck dissection for early stage oropharyngeal squamous cell carcinoma implemented at a Danish head and neck cancer center: a phase II trial on feasibility and tumour margin status.

There is an increasing incidence of oropharyngeal squamous cell carcinoma (OPSCC) in the western world due to human papillomavirus (HPV). According to the Danish Head and Neck Cancer Group guidelines, the current recommended treatment of patients with OPSCC in Denmark is primary radiation therapy (RT) with or without concomitant chemotherapy. This is the first study in Scandinavia from a head and neck cancer centre that aims to demonstrate the feasibility of performing primary transoral robotic surgery (TORS) and concurrent neck dissection for patients with early stage OPSCC. Between September 2014 and January 2016, 30 consecutive patients with clinical T1-T2, N0-N1 OPSCC underwent primary TORS and concurrent neck dissection. The patients were offered postoperative adjuvant therapy according to pathological risk parameters: pT >2, T-site margin <2 mm, pN >1 or extracapsular extension (ECE). Concomitant chemotherapy was offered to patients with the presence of ECE or involved margins. Twenty-nine patients had negative margins on T-site after primary resection. Only one patient had a close margin of 1 mm. Unilateral neck dissection was performed in 21 patients while nine patients underwent bilateral neck dissection. Due to an upstaging following surgery, 13 patients were referred to adjuvant therapy. Four of these patients received RT and two patients received concomitant chemo-radiation (CCR) therapy. Seven patients declined the recommended adjuvant therapy one of whom later developed an N-site recurrence and received salvage surgery with postoperative RT. In summary, 43% of the patients were referred to adjuvant therapy following primary surgery which was mainly due to N-site stage migration and ECE. Primary TORS and concurrent neck dissection is a safe and feasible procedure that may be an alternative to primary RT and CCR in a selected group of patients with early stage OPSCC.

The association between human papillomavirus and oropharyngeal squamous cell Carcinoma: Reviewed according to the Bradford Hill criteria for causality.

There is emerging evidence of the association between human papillomavirus and a subset of head and neck cancers. However, the role of human papillomavirus as a causal factor is still debated. This review addresses the association between human papillomavirus and oropharyngeal squamous cell carcinoma using the Bradford Hill criteria. The strength of the association is supported by, detection of human papillomavirus infection and antibodies prior to oropharyngeal squamous cell carcinoma. This is furthermore reinforced by the absence of human papillomavirus DNA in healthy tonsils. The association is geographically consistent throughout the economically developed world. The presence and integration of high-risk human papillomavirus genome in tonsillar tumours, and expression of viral oncogenes, are specific and plausible. Analogous to human papillomavirus in cervical cancer, the rising incidence in human papillomavirus positive oropharyngeal squamous cell carcinoma is associated with sexual behaviour. These associations have been repeatedly observed and are in accordance with our current knowledge. The time relation between cause and effect remains the main challenge, due to the lack of well-defined premalignant lesions. However, a causal relationship between human papillomavirus infection and oropharyngeal squamous cell carcinoma seems evident.

Validation study of HPV DNA detection from stained FNA smears by polymerase chain reaction: Improving the diagnostic workup of patients with a tumor on the neck.

BACKGROUND: Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) often presents with cystic cervical metastasis and a small primary tumor localized in the palatine tonsils or base of the tongue, which is diagnostically challenging. Testing for HPV DNA in fine-needle aspiration (FNA) smears from metastases may facilitate a targeted diagnostic workup for identifying the primary tumor. This study was designed to assess the ability to detect HPV DNA in FNA smears with polymerase chain reaction (PCR). METHODS: May-Grünvald-Giemsa (MGG)-stained FNA smears from metastases and corresponding surgical specimens were collected from 71 patients with known HPV-positive OPSCC, 12 patients with oral squamous cell carcinoma (OSCC), 20 patients with branchial cleft cysts, and 20 patients with Warthin tumors. Thirty-eight patients with OPSCC and 7 patients with OSCC had FNA smears available from metastases and also surgical specimens from the primary tumor and the metastases. The scraped cell material from FNA smears and corresponding surgical specimens were analyzed for HPV DNA by PCR. p16 immunohistochemistry was performed on surgical specimens from the carcinomas. RESULTS: HPV DNA was detected in 68 of the 71 FNA smears from OPSCC metastases. All corresponding surgical specimens from primary tumors (n = 71) and metastases (n = 38) were p16- and HPV DNA-positive. All the surgical specimens and corresponding FNA smears from OSCCs, Warthin tumors, and branchial cleft cysts were HPV DNA-negative. The sensitivity and specificity were 94.7% and 100%, respectively. CONCLUSIONS: The detection of HPV DNA in MGG-stained FNA smears by PCR is a valid method that could be implemented in routine clinical practice. Cancer Cytopathol 2016;124:820-7. © 2016 American Cancer Society.

The role of human papillomavirus in head and neck cancer.

Over the last 20 years, there has been increasing awareness of a subset of squamous cell carcinomas of the head and neck (HNSCC), i.e. HPV-positive HNSCC. These cancers seem to differ somewhat from HPV-negative HNSCC. Patients with HPV-positive HNSCC tend to be younger and have a lower intake of tobacco and alcohol. Distinct molecular profiles separate them from HPV-negative cancers and show similarities with HPV-positive cervical SCC. There is evidence that HPV-positive HNSCC is a sexually transmitted disease. Patients with HPV-positive HNSCC are often diagnosed at a late stage with large cystic lymph nodes in the neck. HPV-positive HNSCC show an affinity for the oropharynx, especially the tonsils and the base of the tongue, and tend to show low differentiation histopathologically. There is a better prognosis regardless of the treatment regimen for HPV-positive HNSCC compared with HPV-negative HNSCC, and this seems to be related to the immune system. Whether the new vaccines for HPV will protect not only against cervical cancer but also against HPV-positive HNSCC remains unknown.

[Photodynamic therapy for head and neck cancer]. / Fotodynamisk terapi af hoved-hals-kraeft.

Photodynamic therapy (PDT) is a new treatment for head and neck cancer. The principle of the treatment is a photochemical reaction initiated by light activation of a photosensitizer, which causes the death of the exposed tissue. This article presents the modes of action of PDT and the techniques as well as the clinical procedure. A critical review of the literature is also presented, regarding treatment results of the different techniques and indications for treatments. The possibilities for PDT for head and neck cancer in Denmark are mentioned.