Diagnostic accuracy of in vivo early tumor imaging from probe-based confocal laser endomicroscopy versus histologic examination in head and neck squamous cell carcinoma.

OBJECTIVES: Probe-based confocal laser endomicroscopy (pCLE) is a noninvasive and real-time imaging technique allowing acquisition of in situ images of the tissue microarchitecture during oral surgery. We aimed to assess the diagnostic performance of pCLE combined with patent blue V (PB) in improving the management of early oral cavity, oro/hypopharyngeal, and laryngeal cancer by imaging squamous cell carcinoma in vivo. MATERIALS AND METHODS: The prospective study enrolled 44 patients with early head and neck lesions. All patients underwent white-light inspection or panendoscopy depending on the lesion's location, followed by pCLE imaging of the tumor core and its margins after topical application of PB. Each zone imaged by pCLE was interpreted at distance of the exam by three pathologists blinded to final histology. RESULTS: Most imaged zones could be presented to pathologists; the final sensitivity and specificity of pCLE imaging in head and neck cancers was 73.2-75% and 30-57.4%, respectively. During imaging, head and neck surgeons encountered some challenges that required resolving, such as accessing lesions with the flexible optical probe, achieving sufficiently precise imaging on the targeted tissues, and heterogeneous tissue staining by fluorescent dye. CONCLUSION: Final sensitivity scores were reasonable but final specificity scores were low. pCLE zones used to calculate specificity were acquired in areas of tumor margins, and the poor quality of the images acquired in these areas explains the final low specificity scores. CLINICAL RELEVANCE: Practical adjustments and technical training are needed to analyze head and neck lesions in various anatomical sites in real-time by pCLE.

Value of Full-Field Optical Coherence Tomography Imaging for the Histological Assessment of Head and Neck Cancer.

BACKGROUND AND OBJECTIVES: In head and neck surgery, intraoperative and postoperative evaluation of tumor margins is achieved by histopathological assessment, which is a multistep process. Intraoperative analysis of tumor margins to obtain a preliminary diagnosis is usually carried out on frozen sections. Analysis of frozen sections is challenging due to technical difficulties in processing. Full-field optical coherence tomography (FFOCT) provides ex vivo images of fresh tissue samples at a microscopic scale without tissue processing. The objectives of our study were to define the diagnostic criteria required to interpret head and neck FFOCT images and to evaluate the reliability of a histological diagnosis made on an "optical biopsy" produced by head and neck FFOCT imaging compared with conventional histology. STUDY DESIGN/MATERIALS AND METHODS: First, we established an atlas of comparative images (FFOCT/standard histology) and defined the diagnostic criteria based on FFOCT images. Two pathologists subsequently performed a blinded review on 57 FFOCT images (32 patients). Specificity and sensitivity were measured by comparison with the standard histological diagnosis. The primary endpoint was major concordance, defined as two classifications leading to the same therapeutic decision (treatment/no treatment). RESULTS: Pathologists identified four main criteria for tissue diagnosis on FFOCT images: heterogeneous cell distribution, stromal reaction, coiling, and keratinization abnormalities. The correlation study showed good results, with sensitivity from 88% to 90% and specificity from 81% to 87%, regardless of whether the FFOCT image review was performed by a pathologist with or without previous experience in optical imaging. CONCLUSIONS: Our results demonstrate that FFOCT images can be used by pathologists for differential diagnosis, and that high-resolution FFOCT imaging can provide an assessment of microscopic architecture in head and neck tissues without tissue processing requirements. Lasers Surg. Med. © 2020 Wiley Periodicals, Inc.

Laser debulking or tracheotomy in airway management prior to total laryngectomy for T4a laryngeal cancer.

PURPOSE: Retrospective studies have shown that tracheotomy prior to total laryngectomy (TL) is associated with decreased survival. We sought to investigate whether this is due to higher local invasiveness associated with obstructive disease or whether it is the result of tracheotomy itself. METHODS: We reviewed patients with a T4a (AJCC 7th edition) laryngeal squamous-cell carcinoma treated with a primary TL followed by adjuvant radiotherapy between 2001 and 2013. We compared patients who had obstructive lesions with those who had non-obstructive lesions in terms of preoperative data, pathological features, and treatment outcomes. Second, we compared tracheotomized patients with patients who underwent endoscopic laser debulking (ELD). RESULTS: One hundred patients were reviewed. Thirty-seven of them required an airway intervention prior to a TL (tracheotomy n = 24/ELD n = 13). Patients with obstructive tumors had more frequently subglottic extension (p = 0.0066) and a shorter disease-free survival (DFS) (p = 0.046), due to a higher incidence of additional distant metastases. Tracheotomy was associated with a shorter DFS (p = 0.035) and more frequent perineural invasion (p = 0.0272) as compared to ELD, but not with a higher incidence of stomal recurrence. CONCLUSIONS: A tracheotomy prior to a total laryngectomy is associated with decreased survival. We recommend laser debulking as the preferred treatment whenever management of an obstructive airway is required prior to a total laryngectomy.

Outcomes and prognostic factors for squamous cell carcinoma of the oral tongue in young adults: a single-institution case-matched analysis.

There is controversy regarding prognosis and treatment of young patients with oral cavity cancer compared to their older counterparts. We conducted a retrospective case-matched analysis of all adult patients younger than 40 years and treated at our institution for a squamous cell carcinoma of the oral cavity. Only non-metastatic adult patients (age >18) with oral tongue cancer were eventually included and matched 1:1 with patients over 40 years of age, at least 20 years older than the cases, with same T and N category and treatment period. Sixty-three patients younger than 40 had an oral cavity squamous cell cancer out of which 57 had an oral tongue primary during the period 1999-2012, and 50 could be matched with an older control. No difference could be seen between younger and older patients with regard to overall, cancer-specific, or progression-free survival. The patterns of failure were similar, although in young patients, almost all failures occurred during the first 2 years following treatment. Although overall survival shows a trend toward lower survival in older patients, cancer-specific survival and analysis of pattern failure suggest that disease prognosis is similar between young and older adults with oral tongue cancer. Further work is needed to identify the younger patients with poorer prognosis who overwhelmingly fail during the first year after treatment and could benefit from treatment intensification. Until then, young adults ought to be treated using standard guidelines.

Intraoperative Near-infrared Imaging for Parathyroid Gland Identification by Auto-fluorescence: A Feasibility Study.

BACKGROUND: Parathyroid glands (PGs) can be particularly hard to distinguish from surrounding tissue and thus can be damaged or removed during thyroidectomy. Postoperative hypoparathyroidism is the most common complication after thyroidectomy. Very recently, it has been found that the parathyroid tissue shows near-infrared (NIR) auto-fluorescence which could be used for intraoperative detection, without any use of contrast agents. The work described here presents a histological validation ex vivo of the NIR imaging procedure and evaluates intraoperative PG detection by NIR auto-fluorescence using for the first time to our knowledge a commercially available clinical NIR imaging device. METHODS: Ex vivo study on resected operative specimens combined with a prospective in vivo study of consecutive patients who underwent total or partial thyroid, or parathyroid surgery at a comprehensive cancer center. During surgery, any tissue suspected to be a potential PG by the surgeon was imaged with the Fluobeam 800 (®) system. NIR imaging was compared to conventional histology (ex vivo) and/or visual identification by the surgeon (in vivo). RESULTS: We have validated NIR auto-fluorescence with an ex vivo study including 28 specimens. Sensitivity and specificity were 94.1 and 80 %, respectively. Intraoperative NIR imaging was performed in 35 patients and 81 parathyroids were identified. In 80/81 cases, the fluorescence signal was subjectively obvious on real-time visualization. We determined that PG fluorescence is 2.93 ± 1.59 times greater than thyroid fluorescence in vivo. CONCLUSIONS: Real-time NIR imaging based on parathyroid auto-fluorescence is fast, safe, and non-invasive and shows very encouraging results, for intraoperative parathyroid identification.

Diagnosis of HPV-driven head and neck cancer with a single test in routine clinical practice.

Accurate screening of HPV-driven head and neck squamous cell carcinoma is a critical issue. Although there are commercial direct and indirect assays for HPV-related head and neck squamous cell carcinoma, none are ideal. Recently, a novel RNA in situ hybridization test (the RNAscope HPV-test) has been developed for the detection of high-risk HPV E6/E7 mRNA in formalin-fixed paraffin-embedded tissue. However, validation of this assay against the 'gold standard' (identification of high-risk HPV E6/E7 mRNA in fresh-frozen tissue by quantitative real-time (qRT)-PCR) has only been reported by one team. Formalin-fixed paraffin-embedded samples from 50 patients with tonsil or tongue base carcinoma were tested using the RNAscope HPV-test, p16 immunohistochemistry, and chromogenic in situ hybridization for high-risk HPV-DNA. The results were compared with those of qRT-PCR on matched fresh-frozen samples. Compared with the reference test, the sensitivity, specificity, positive, and negative predictive values of the RNAscope HPV-test and of p16 immunohistochemistry were 93%, 94%, 96%, 88% and 96%, 93%, 96%, and 93%, respectively. Five cases were discrepant between the RNAscope HPV-test and p16-immunohistochemisrty. The RNAscope HPV-test demonstrated excellent analytical performance against the 'gold standard' and is easier to interpret than chromogenic in situ hybridization. p16-immunohistochemistry also performed very well, however its main weakness is that it is an indirect marker of the presence of HPV. These data suggest that the RNAscope HPV-test is a promising test that could be developed as a clinical standard for the precise identification of HPV-driven oropharyngeal squamous cell carcinoma.

Red and far-red fluorescent dyes for the characterization of head and neck cancer at the cellular level.

BACKGROUND: Primary upper aerodigestive tract malignancy remains a cancer having a poor prognosis, despite current progress in treatment, due to a generally late diagnosis. OBJECTIVES: We conducted a preliminary assessment of five dyes approved for human use for the imaging of head and neck tissues at the cellular level, which could be considered for clinical examination. METHODS: We investigated fluorescence endomicroscopic images on fresh samples obtained from head and neck surgeries after staining with hypericin, methylene blue, toluidine blue, patent blue or indocyanine green to provide a preliminary consideration as to whether these images contain enough information for identification of non-pathologic and pathologic tissues. The distribution pattern of dye has been examined using probe-based confocal laser endomicroscopy (pCLE) in ex vivo specimens and compared with corresponding histology. RESULTS: In most samples, the image quality provided by pCLE with both dyes allowed pathologists to recognize histological characteristics to identify the tissues. CONCLUSION: The combination of pCLE imaging with these dyes provides interpretable images close to conventional histology; a promising clinical tool to assist physicians in examination of upper aerodigestive tract, as long as depth imaging issues can be overcome.

HPV-related oropharyngeal squamous cell carcinomas: a comparison between three diagnostic approaches.

PURPOSE: HPV-related oropharyngeal squamous cell carcinomas clearly represent a growing entity in the head and neck with distinct carcinogenesis, clinico-pathological presentation and survival profile. We aimed to compare the HPV prevalence rates and clinico-pathological correlations obtained with three distinct commonly used HPV detection methods. MATERIALS AND METHODS: p16-immunohistochemistry (IHC), HPV DNA viral load by real-time PCR (qPCR), and HPV genotyping by a reverse hybridization-based line probe assay (INNO-LiPA) were performed on pretreatment formalin-fixed paraffin-embedded tumor samples from 46 patients treated for single primary oropharyngeal carcinomas. RESULTS: Twenty-eight patients (61%) had a p16 overexpression in IHC. Twenty-nine patients (63%) harbored HPV DNA on qPCR. Thirty-four patients (74%) harbored HPV DNA on INNO-LiPA. The concordance analysis revealed a good agreement between both HPV DNA detection methods (κ=0.65); when both tests were positive, the depicted HPV subtypes were always concordant (HPV16 in 27 cases, HPV18 in 1 case). Agreement was moderate between IHC and qPCR (κ=0.59) and fair between IHC and INNO-LiPA (κ=0.22). CONCLUSIONS: Certain highly sensitive methods are able to detect the mere presence of HPV without any carcinogenetic involvement while other more specific tests provide proof of viral transcriptional activity and thus evidence of clinically relevant infections. The use of a stepwise approach allows reducing false positives; p16-immunostaining seems to be an excellent screening test and in situ hybridization may overcome some of the PCR limitations.

Salivary gland carcinoma: Towards a more personalised approach.

Salivary Gland carcinomas (SGCs) are rare tumors accounting for less than 1% of all cancers with 21 histologically diverse subtypes. The rarity of the disease presents a challenge for clinicians to conduct large size randomized controlled trials. Surgery and radiotherapy remain the only curative treatment for localized disease, whereas treatments for recurrent and metastatic disease remain more challenging with very disappointing results for chemotherapy. The different histological subtypes harbor various genetic alterations, some pathognomonic with a diagnostic impact for pathologists in confirming a difficult diagnosis and others with therapeutic implications regardless of the histologic subtype. Current international guidelines urge pathologists to identify androgen receptor status, HER-2 expression that could be determined by immunohistochemistry, and TRK status in patients with non-adenoid cystic salivary gland carcinoma that are eligible to initiate a systemic treatment, in order to offer them available targeted therapies or refer them to clinical trials based on their mutational profile. A more advanced molecular profiling by next generation sequencing would offer a larger panel of molecular alterations with possible therapeutic implications such as NOTCH, PI3K, BRAF, MYB, and EGFR. In the following review, we present the most common genetic alterations in SGCs as well as actionable mutations with the latest available data on therapeutic options and upcoming clinical trials.

Ultra-fast confocal fluorescence microscopy for neck lymph node imaging in head and neck cancer.

OBJECTIVES: We evaluated ultra-fast confocal fluorescence microscopy (UFCM) as a new modality for pathology practice in head and neck cancer (HNC). This was assessed through an ex vivo study to estimate the accuracy, specificity, and sensitivity of interpretation of UFCM images by pathologists for the detection of metastatic lymph nodes in HNC patients undergoing sentinel lymph node biopsy or selective or complete neck dissection. MATERIALS AND METHODS: 44 patients with 32 cN0 and 12 cN+ HNC were included. The macroscopically non-invaded fresh bisected lymph nodes were stained with acridine orange and imaged with Histolog® Scanner (UFCM). Two pathologists interpreted independently the UFCM images postoperatively and gave a consensus diagnosis in case of disagreement. The gold standard was the diagnosis based on hematoxylin-eosin-saffron (HES) sections. RESULTS: 201 lymph nodes were imaged by UFCM. Thirty nodes (15 %) were invaded on final histology: 3 with micrometastases and 27 with macrometastases. The concordance rate between the pathologists on the UFCM images was 192/201 = 95.5 % and the Cohen kappa coefficient was 0.80. The accuracy of UFCM was 95.5 % (95 %CI: 91.7 %-97.9 %) with a high specificity at 98.8 % (95 %CI: 95.8 %-99.9 %) but an insufficient sensitivity at 76.7 % (95 %CI: 57.7 %-90.1 %). The three micrometastases and four of the 27 macrometastases were missed on UFCM images. CONCLUSION: The UFCM is providing promising detection values with a very good specificity and moderate sensitivity carrying room for improvement.

Immunodetection of NUT Protein: Implementation, Indications, and Results in a Tertiary Reference Center.

The immunodetection of NUT protein is a reliable tool to identify NUT carcinoma, a rare and still underdiagnosed tumor entity. The technique was implemented in 2017 in our department, a tertiary reference center with a large recruitment in all tumor types, including head and neck and thoracic tumors. We evaluated its use over a 6-year period (2017-2022) to (a) describe the indications for the technique, (b) determine the number of NUT carcinomas detected and confirmed by Fluorescence in situ hybridization, and (c) describe briefly the characteristics of these tumors. Over the study period, 382 NUT immunodetections were performed; the annual number of requests varied from 45 to 83. All 21 pathologists of the department made at least one request (range: 1 to 94; annual mean: 18.2). 54.7% of immunodetections were performed for internal cases, 37% for cases submitted for consultation, and 8.3% for cases submitted for confirmation of a suspected diagnosis. The main indications were poorly differentiated tumors of the head and neck region (39%) and the thorax (19.6%), and difficult-to-classify soft tissue tumors (11.8%). Twelve cases of NUT carcinoma were detected by immunohistochemistry and confirmed by Fluorescence in situ hybridization. Seven were from the head and neck region (4.7% of the tumors tested), 4 from lung or mediastinum (5.3%), 1 from an unknown primary at the time of diagnosis. In conclusion, the implementation of NUT immunodetection in the daily workflow of a pathology department improves the detection of NUT carcinoma. This becomes essential with the emergence of potential targeted therapies.

Breast tissue imaging atlas using ultra-fast confocal microscopy to identify cancer lesions.

New generation ultra-fast fluorescence confocal microscopy (UFCM) allows to image histological architecture of fresh breast tissue and may be used for ex vivo intraoperative analysis for margin status. The criteria to identify breast tumoral and non-tumoral tissues in UFCM images are still objects of investigation. The objective of the study was to create an atlas of ex vivo UFCM images of breast tissues and breast carcinomas based on the first extensive collection of large field-of-view UFCM breast images. One hundred sixty patients who underwent conserving surgery for breast cancer were included. Their fresh surgical specimens were sliced, stained with acridine orange, and imaged at high resolution with large-field-of-view UFCM. The resulting images were digitally false colored to resemble frozen sections. Each UFCM image was correlated with the corresponding definitive histology. Representative images of normal tissue, inflammation, benign lesions, invasive carcinoma (IC), and ductal carcinoma in situ (DCIS) were collected. A total of 320 large-field images were recorded from 58 IC of no special type, 44 invasive lobular carcinomas, 1 invasive mucinous carcinoma, 47 DCIS, 2 lobular carcinomas in situ, and 8 specimens without cancer. Representative images of the main components of the normal breast and the main types of ICs and DCIS were annotated to establish an UFCM atlas. UFCM enables the imaging of the fresh breast tissue sections. Main morphological criteria defined in traditional histopathology such as tissue architecture and cell features can be applied to describe UFCM images content. The generated atlas of the main normal or tumoral tissue features will support the adoption of this optical technology for the intraoperative examination of breast specimens in clinical practice as it can be used to train physicians on UFCM images and develop artificial intelligence algorithms. Further studies are needed to document rare breast lesions.

HPV-driven oropharyngeal cancer burden in Paris and its region (ILE DE FRANCE) from 1981 TO 2021.

BACKGROUND: France has the sixth highest incidence of oropharyngeal cancer (OPC) in Europe, but the epidemiological impact of high-risk HPV (HR-HPV) remains poorly documented. The objective of our study was to assess the proportion of OPCs caused by HR-HPV in Paris, and its suburbs, over the four past decades. This area accounts for almost one-fifth of the total population of France. METHODS: OPCs diagnosed in 1981, 1986, 1991, 1996, 2001, 2006, 2011, 2016 and 2020/2021 in two of the main referral cancer centers for HNCs in Paris and its suburbs were retrieved from the tumor biobanks. HPV status was determined by p16-staining and HPV-DNA detection. Samples were considered HPV-driven if both assays were positive. Results were compared to the French cancer registry data. RESULTS: Samples from 697 OPC patients were assessed (including 82 % of all samples diagnosed in 2001, 2006, 2011, 2016, 2021). The proportion of HPV-driven cases rose from 2.7 % to 53 % between 1981 and 2021. HPV16 was the dominant genotype during the study period. Of patients with HPV-driven OPC, 81 % were male and 42 % were smokers versus 80 % and 92 % in their HPV-negative counterparts. The age of OPC patients increased significantly, during the study period, independent of their HPV status CONCLUSION: The proportion of HPV-driven OPCs has significantly increased in Paris and its suburbs, during the last four decades. OPCs has become the 2nd predominant type of head and neck cancer, in France. This may be linked to the rise in HPV-driven cases and the decrease of tobacco and alcohol consumption in men.

Epithelial-Myoepithelial Carcinoma of the Maxilla Arising From Minor Salivary Glands of Hard Palate: A Rare Case Report.

Epithelial-myoepithelial carcinoma is a rare malignant neoplasm of salivary glands. It is specifically found in the major salivary glands. The cases that emerge from minor salivary glands are rarely described. Histologically, it commonly exhibits a characteristic biphasic pattern consisting of epithelial and myoepithelial components. The histopathological resemblance to other benign and malignant neoplasms that also display myoepithelial characteristics makes the differential diagnosis challenging. Each differential diagnosis requires a very different management approach. Considering the difficulties of anatomopathological diagnosis and the rarity of epithelial-myoepithelial carcinomas emerging from minor salivary glands, we report a rare epithelial-myoepithelial carcinoma case of minor salivary glands in a 58-year-old woman. She was referred for a palatal swelling, evolving for more than 35 years, and reported recent pain and nasal obstruction. The mucosal swelling was located in the left maxilla within the hard palate, of a 45-mm-long axis crossing the medial line and extending to the premaxilla, without cervical lymph node involvement. A computed tomography scan revealed a palatal lesion involving the left and the right maxilla. Furthermore, the superior alveolar process, both left and right maxillary sinuses, the nasal cavities, and the nasal septum were included in the lesion. The final diagnosis was difficult to confirm despite multiple biopsies and was determined only from the excised specimen. The diagnosis of this tumor was challenging due to the clinical and histological similarities with other salivary tumors. The aim of this case report is to shed light on the distinctive features of these tumors and explore optimal screening and related management strategies.

Intraoperative Autofluorescence Imaging for Parathyroid Gland Identification during Total Laryngectomy with Thyroidectomy.

OBJECTIVE: Hypoparathyroidism is a known complication of total laryngectomy, although parathyroid preservation and/or reimplantation are not routine. Autofluorescence is a new technique for identifying parathyroid glands intraoperatively. The aim of this study was to evaluate the feasibility of autofluorescence in this context. MATERIALS AND METHODS: A retrospective study of patients undergoing total laryngectomy/pharyngectomy with concomitant thyroidectomy using the Fluobeam® (Fluoptics, Grenoble, France) and frozen section of a parathyroid fragment in case of reimplantation. The rates of identification using autofluorescence, reimplantation, and hypoparathyroidism were evaluated. RESULTS: Eighteen patients (16 males, median age 67) underwent total laryngectomy/pharyngectomy with total thyroidectomy (n = 12) or hemithyroidectomy (n = 6). A median of 2 parathyroid glands were identified per patient. Ninety-two percent were identified by autofluorescence before visualisation. All parathyroids were reimplanted due to devascularization. Temporary hypoparathyroidism occurred in nine patients, and was permanent in one patient. After 34 months of median follow-up (range 1-49), no tumor recurrence was observed in the reimplantation sites. CONCLUSIONS: To our knowledge, this is the largest study to evaluate autofluorescence during total laryngectomy with thyroidectomy. No tumor recurrence occurred in the sites of parathyroid reimplantation.

Breast carcinoma detection in ex vivo fresh human breast surgical specimens using a fast slide-free confocal microscopy scanner: HIBISCUSS project.

BACKGROUND: New generation ultra-fast fluorescence confocal microscopy allows the ex vivo intraoperative analysis of fresh tissue. The High resolution Imaging for Breast carcInoma detection in ex vivo Specimens after breast Conserving sUrgery by hiStolog Scanner (HIBISCUSS) project aimed to develop an online learning program to recognize the main breast tissue features on ultra-fast fluorescence confocal microscopy images and to evaluate the performance of surgeons and pathologists in diagnosing cancerous and non-cancerous breast tissue in ultra-fast fluorescence confocal microscopy images. METHODS: Patients who underwent conservative surgery or mastectomy for breast carcinoma (invasive or in situ lesions) were included. The fresh specimens were stained with a fluorescent dye and imaged using a large field-of-view (20 cm2) ultra-fast fluorescence confocal microscope. RESULTS: One hundred and eighty-one patients were included. The images from 55 patients were annotated to generate learning sheets and images from 126 patients were blindly interpreted by seven surgeons and two pathologists. The time for tissue processing and ultra-fast fluorescence confocal microscopy imaging was between 8 and 10 min. The training program was composed of 110 images divided into nine learning sessions. The final database for blind performance assessment comprised 300 images. The mean duration for one training session and one performance round was 17 and 27 min respectively. The performance of pathologists was almost perfect with 99.6 per cent (standard deviation (s.d.) 5.4 per cent) accuracy. Surgeons' accuracy significantly increased (P = 0.001) from 83 per cent (s.d. 8.4 per cent) in round 1 to 98 per cent (s.d. 4.1 per cent) in round 7 as well as the sensitivity (P = 0.004). Specificity increased without significance from 84 per cent (s.d. 16.7 per cent) in round 1 to 87 per cent (s.d. 16.4 per cent) in round 7 (P = 0.060). CONCLUSION: Pathologists and surgeons showed a short learning curve in differentiating breast cancer from non-cancerous tissue in ultra-fast fluorescence confocal microscopy images. Performance assessment for both specialties supports ultra-fast fluorescence confocal microscopy evaluation for intraoperative management. REGISTRATION NUMBER: NCT04976556 (http://www.clinicaltrials.gov).

Prognostic Analysis of HPV Status in Sinonasal Squamous Cell Carcinoma.

Sinonasal squamous cell carcinoma (SNSCC) is a rare and aggressive malignancy with poor prognosis. Human papilloma virus (HPV) can induce SNSCC although its incidence and impact on patients' outcomes remains unclear. We performed a retrospective cohort study of patients with SNSCC treated consecutively in a comprehensive cancer center. HPV status was determined with p16 immunohistochemistry followed by RNA in situ hybridization (RNAscope). The incidence, clinical characteristics, and oncologic outcomes of HPV+SNSCC were assessed. P16 prognostic value was evaluated. Fifty-nine patients were included. Eleven (18.6%) SNSCC were p16+ with five (8.4%) doubtful cases. RNAscope was positive in nine cases (15.2%). Patients with HPV+SNSCC were younger (p = 0.0298) with a primary tumor originating mainly in nasal fossa (p < 10−4). Pathologic findings were not different according to HPV status. Among patients who were curatively treated, overall survival was better for HPV+SNSCC (p = 0.022). No prognostic value of p16 expression was reported. Patients with HPV+SNSCC have better oncologic outcomes, probably due to earlier tumor stage with primary location predominantly in the nasal fossa, a more suitable epicenter to perform a surgical resection with clear margins. P16 expression seems not to be a good surrogate of HPV status in SNSCC.

Confocal laser endomicroscopy and confocal microscopy for head and neck cancer imaging: Recent updates and future perspectives.

Confocal laser endomicroscopy (CLE) is a promising technology that provides real-time histological visualization of living tissue, described as "optical biopsy". It has been used successfully in dermatology, gastroenterology and ophthalmology for clinical diagnosis and tumor margin assessment. In addition to in vivo tissue assessment, confocal microscopy can also be used ex vivo on freshly excised or fixed tissue for intraoperative tumor margin assessment. While CLE and ex vivo confocal microscopy (EVCM) have shown promising results for the identification of head and neck cancers at cell level, several methodological issues need to be addressed before they can be widely used in routine clinical use. The present review will focus on recent advances in CLE and EVCM in the diagnosis and management of head and neck cancer and discuss remaining challenges for their clinical application.

A loss-of-function polymorphism in ATG16L1 compromises therapeutic outcome in head and neck carcinoma patients.

The anticancer immune response is shaped by immunogenic cell stress and death pathways. Thus, cancer cells can release danger-associated molecular patterns that act on pattern recognition receptors expressed by dendritic cells and their precursors to elicit an antitumor immune response. Here, we investigated the impact of single nucleotide polymorphisms (SNPs) in genes affecting this cancer-immunity dialogue in the context of head and neck squamous cell carcinoma (HNSCC). We observed that homozygosity for a loss-of-function SNP (rs2241880, leading to the substitution of a threonine residue in position 300 by an alanine) affecting autophagy related 16 like 1 (ATG16L1) is coupled to poor progression-free survival in platinum-treated HNSCC patients. This result was obtained on a cohort of patients enrolled at the Gustave Roussy Cancer Campus and was validated on an independent cohort of The Cancer Genome Atlas (TCGA). Homozygosity in rs2241880 is well known to predispose to Crohn's disease, and epidemiological associations between Crohn's disease and HNSCC have been reported at the levels of cancer incidence and prognosis. We speculate that rs2241880 might be partially responsible for this association.

Patterns of disease events and causes of death in patients with HPV-positive versus HPV-negative oropharyngeal carcinoma.

BACKGROUND AND PURPOSE: There have been no studies to date of patterns of events after oropharyngeal squamous cell carcinoma (OPC) treatment comprising disease progression immediately after treatment or after a disease-free interval (DFI), and causes of death, according to HPV status. MATERIALS AND METHODS: Patients with a T1-4, N0-3, M0 OPC who completed treatment in a curative intent at our center between 2011 and 2020 were analyzed. A DFI was defined as the absence of the disease confirmed by both physical and radiological evaluation. RESULTS: We analyzed 888 patients, of who 451 were p16-positive and 437 were p16-negative. The 5-year survival rates were 82.4% vs. 44%, respectively (p < 0.0001, HR 0.24). The rates of disease progression at the end of the treatment without a DFI were 7.8% vs. 21.1% in the p16-positive vs. the p16-negative patients (p < 0.0001, OR 0.38). The 5-year competing risks of disease recurrence after a DFI were 5.6% vs. 20.5%, respectively (p < 0.0001, HR 0.26). Patients who were p16-positive had a lower risk of death from OPC disease (p < 0.0001, HR 0.23). The 5-year competing risks of a second primary cancer during follow-up were 16.1% vs. 49.9% (p = 0.0002) in the p16-positive vs. the p16- negative patients. Patients who were p16-positive had a lower risk of death from intercurrent causes (p < 0.0001, HR 0.17). CONCLUSION: Clinical trials and medical interventions dedicated to each category of events and causes of death are needed to improve survival in HPV-positive and HPV-negative OPC patients.