[Fat embolism in common carotid artery following temporal autologous fat graft]. / Embolie graisseuse carotidienne dans les suites d'un lipofilling temporal.

Lipofilling is a well-known procedure, initially described by Coleman in 1991. Many cases of fat embolism following this procedure are published. Our patient had a common carotid fat embolism after a temporal autologous fat graft.

Validation of a Three-Dimensional Head and Neck Spheroid Model to Evaluate Cameras for NIR Fluorescence-Guided Cancer Surgery.

Near-infrared (NIR) fluorescence-guided surgery is an innovative technique for the real-time visualization of resection margins. The aim of this study was to develop a head and neck multicellular tumor spheroid model and to explore the possibilities offered by it for the evaluation of cameras for NIR fluorescence-guided surgery protocols. FaDu spheroids were incubated with indocyanine green (ICG) and then included in a tissue-like phantom. To assess the capability of Fluobeam® NIR camera to detect ICG in tissues, FaDu spheroids exposed to ICG were embedded in 2, 5 or 8 mm of tissue-like phantom. The fluorescence signal was significantly higher between 2, 5 and 8 mm of depth for spheroids treated with more than 5 µg/mL ICG (p < 0.05). The fluorescence intensity positively correlated with the size of spheroids (p < 0.01), while the correlation with depth in the tissue-like phantom was strongly negative (p < 0.001). This multicellular spheroid model embedded in a tissue-like phantom seems to be a simple and reproducible in vitro tumor model, allowing a comparison of NIR cameras. The ideal configuration seems to be 450 µm FaDu spheroids incubated for 24 hours with 0.05 mg/ml of ICG, ensuring the best stability, toxicity, incorporation and signal intensity.

HPV insertional pattern as a personalized tumor marker for the optimized tumor diagnosis and follow-up of patients with HPV-associated carcinomas: a case report.

BACKGROUND: In clinical oncology, only a few applications have been developed using HPV as a personalized tumor marker, a lack most probably related to the limited information obtained by the classical Polymerase Chain Reaction (PCR) approach. To overcome this limitation, we have recently developed the capture-based Next-Generation Sequencing (NGS) "CaptHPV" assay, designed to provide an extensive and comprehensive molecular characterization of HPV DNA sequences associated with neoplasias, ie the sequence of the viral genome (245 genotypes), its physical state, viral load, integration site and genomic alterations at integration locus. These data correspond to highly specific tumor markers that can be used to improve diagnosis and patient's follow-up. CASE PRESENTATION: We report here a case that is a straightforward and practical illustration of the power of the CaptHPV method. A patient developed successively a carcinoma of the anal canal and of the tongue. The two tumors were squamous cell carcinoma, found associated with HPV16 using PCR. In order to document a possible metastasis to the tongue from the anal cancer, we performed CaptHPV analysis on the two tumors. The analysis of the anal carcinoma found 55 viral/human hybrid reads allowing the identification of the HPV16 DNA integration in the 4q25 chromosomal band locus with a 178,808 bp deletion in the cell genome. Molecular analysis of the tongue tumor disclosed 6110 reads of HPV16, with a viral pattern strictly identical to that of the anal tumor. A total of 131 hybrid reads between HPV16 and the cell genome were found, corresponding exactly to the same locus of integration of viral DNA at the 4q25 site. The 178,808 bp genomic deletion was also found in the lingual tumor. The exact identity of HPV insertional signatures in the two tumors, demonstrates unambiguously that the tongue tumor derived from the anal cancer whereas neither histological immunophenotyping nor classical viral analysis using PCR could allow a definitive diagnosis. CONCLUSION: Our observation indicates that the establishment of a detailed cartography of HPV DNA sequences in a tumor specimen provides crucial information for the design of specific biomarkers that can be used for diagnostic, prognostic or predictive purposes.

Partial pharyngolaryngectomy with infrahyoid flap: Our experience.

AIM: We evaluated a cohort of advanced hypopharyngeal squamous cell carcinoma, treated with conservative surgery, reconstruction with infrahyoid flap and radio-chemotherapy. METHODS: We used partial pharyngo-laryngectomy and radio-chemotherapy to treat fifty-seven patients with stage III-IV hypopharyngeal SCC from November 1994 to December 2011. Clinical examination and speech therapy evaluation were used for estimation of laryngeal function. RESULTS: All patients received a partial pharyngo-laryngectomy. All patients underwent neck dissection; 56 patients received bilateral neck dissection. Reconstruction was achieved by infra-hyoid flap. Five-year overall and disease-specific survival rates were 54.4% and 61.4%, respectively. Successful laryngeal function preservation with complete five-year remission was achieved in 44% of the patients. CONCLUSION: Selected even if advanced carcinomas of the hypopharynx maybe treated with partial pharyngo-laryngectomy with reconstruction with pedicled flap. Both oncological and functional results showed a good outcome.

Denosumab-related osteonecrosis of the jaw: A retrospective study.

BACKGROUND: Osteonecrosis of the jaw is a very delicate side effect of Denosumab. The aim of this retrospective study was to assess the occurrence rate of Denosumab-related osteonecrosis of the jaw (DRONJ) at the Cancer Institute of Lorraine (ICL) and to highlight necrosis risk factors. METHODS: To that purpose, we analyzed the medical records of 249 consecutive patients treated with Denosumab at the ICL during the past 5 years. Patients who received orofacial radiotherapy or a previous treatment with a bisphosphonate were excluded. The P-value was set at .005. RESULTS: A total of 141 patients treated at the ICL between January 2010 and December 2015 were included. All patients were treated with XGEVA® . Of the 141 patients included in the study, 10 developed DRONJ. The incidence of DRONJ increases with the duration of follow-up as follows: 3% at 1 year, 7% at 2 years, and 8% from 30 months on. No risk factor for necrosis could be identified except the realization of prior dental extraction (P = .025). CONCLUSION: Our results raise important questions about the dental management of these patients, in particular, concerning the healing period between dental extractions and the initiation of Denosumab.

Multicenter prospective micro-costing study evaluating mandibular free-flap reconstruction.

Free-flap mandibular reconstruction is a highly specialized procedure associated with severe complications necessitating re-interventions and re-hospitalizations. This surgery is expensive in terms of health workers' time, equipment, medical devices and drugs. Our main objective was to assess the direct hospital cost generated by osseocutaneous free-flap surgery in a multicentric prospective micro-costing study. Direct medical costs evaluated from a hospital perspective were assessed using a micro-costing method from the first consultation with the surgeon until the patient returns home, thus confirming the success or failure of the free-flap procedure. The mean total cost for free-flap intervention was 34,009€ (5151-119,604€), the most expensive item being the duration of hospital bed occupation, representing 30-90% of the total cost. In the event of complications, the mean cost increased by 77.3%, due primarily to hospitalization in ICU and the conventional unit. This surgery is effective and provides good results but remains highly complex and costly.

A rare case of extremely high counts of circulating tumor cells detected in a patient with an oral squamous cell carcinoma.

BACKGROUND: Despite aggressive regimens, the clinical outcome of head and neck squamous cell carcinoma remains poor. The detection of circulating tumor cells could potentially improve the management of patients with disseminated cancer, including diagnosis, treatment strategies, and surveillance. Currently, CellSearch(®) is the most widely used and the only Food and Drug Administration-cleared system for circulating tumor cells detection in patients with metastatic breast, colorectal, or prostate cancer. In most cases of head and neck squamous cell carcinoma, only low counts of circulating tumor cells have been reported. CASE PRESENTATION: A 56-year-old white male with no particular medical history, was diagnosed with a squamous cell carcinoma of oral cavity. According to the imaging results (computed tomography and (18)F-fluorodeoxyglucose positron emission tomography / computed tomography) and panendoscopy, the TNM staging was classified as T4N2M0. A non-interruptive pelvimandibulectomy was conducted according to the multidisciplinary meeting advices and the postoperative observations were normal. The patient complained of a painful cervical edema and a trismus 6 weeks after the surgery. A relapse was found by computed tomography and the patient died two weeks later. The search for circulating tumor cells in peripheral venous blood by using the CellSearch(®) system revealed a very high count compared with published reports at three time points (pre-operative: 400; intra-operative: 150 and post-operative day 7: 1400 circulating tumor cells). Of note, all detected circulating tumor cells were epidermal growth factor receptor negative. CONCLUSION: We report here for the first time a rare case of oral squamous cell carcinoma with extremely high circulating tumor cells counts using the CellSearch(®) system. The absolute number of circulating tumor cells might predict a particular phase of cancer development as well as a poor survival, potentially contributing to a personalized healthcare.

Targeted photodynamic therapy in head and neck squamous cell carcinoma: heading into the future.

The aim of this article is to give an insight into the future of photodynamic therapy (PDT) in head and neck squamous cell carcinoma (HNSCC). Through the combination of a photosensitizing agent with light and oxygen, PDT produces highly cytotoxic reactive oxygen species leading to selective tumor eradication. PDT is an attractive treatment for focal therapy of localized tumors, especially in the case of unresectable tumors. In HNSCC, over 1500 patients have been treated by PDT, and the majority of them responded quite favorably to this treatment. However, the non-negligible photosensitization of healthy tissue is a major limitation for the clinical application of PDT. Improvement in tumor selectivity is the main challenge that can be taken up by the use of a new generation of photosensitizing nanoparticles. Passive targeting, by using functionalised nanocarriers to target to overexpressed transmembrane receptors afford attractive solutions. To this day, epidermal growth factor receptor (EGFR) remains the only validated molecular target for HNSCC, and photosensitizer immunoconjugates to EGFR have been developed for the intracellular delivery of photosensitizing agents. Depending on coordinated research between biomarkers, specific ligands, and photosensitizers, similar approaches could be rapidly developed. In addition, some photosensitizers hold high fluorescence yield and therefore could emerge as theranostic agents.

Peptide-mediated targeting of Quantum Dots in a 3D model of head and neck cancer.

BACKGROUND: Oral squamous cell carcinoma (OSCC) treatment mainly relies on surgery. The status of surgical margin is a major prognostic factor for patients as positive margins are associated with lower survival. However, the anatomical particularities of this area complicate margin establishment. Fluorescence guided surgery (FGS) could be employed as an intraoperative technique to improve tumor resection and margin investigation. Quantum dots (QDs) serve as ideal contrast agents in this technique due to their brightness and stability. Since αVß6 integrin is overexpressed in OSCC, coupling QDs with A20FMDV2 peptide (QDs-A20) targeting the αVß6 integrin constitute a real opportunity. This study investigates the accumulation of QDs-A20 in 2D and 3D tongue cancer models, as well as QDs coupled to a scrambled version of this peptide (QDs-Scr) or without peptide (QDs-SPP), for imaging purposes. METHODS: CdSeCdS/ZnS quantum dots were coated with sulfobetaine polymers (QDs-SPP) and conjugated to A20FMDV2 peptide (QDs-A20) or its scrambled version (QDs-Scr). Two-dimensional (2D) and three-dimensional (3D) tongue cancer cells HSC-3 were employed to test the effectiveness of intracellular accumulation of all types of QDs. Targeting ability of each QDs was assessed by flow cytometry, while the depth of penetration into cancerous spheroids was assessed by fluorescence microscopy. RESULTS: QDs coating with sulfobetaines polymers (QDs-SPP) completely prevented their internalization by HSC-3 cells in 2D and 3D models, making QDs stealthy and preventing their non-specific accumulation. Conversely, peptides conjugated QDs (QDs-A20 & QDs-Scr) labeled HSC-3 monolayers and managed to label spheroid periphery up to 23 µm deep. However, no difference in accumulation was found between these two QDs whereas only A20 peptide could potentially target αVß6 integrin. It appears that peptide conjugation increased QDs zeta potential, promoting their adsorption and subsequent endocytosis by cells, independently from αVß6 integrin. CONCLUSIONS: The present study highlighted the impact of peptide conjugation on QDs internalization in 2D and 3D tongue cancer cell models. QDs-SPP were stealthy and did not accumulate in cells. Peptides conjugated QDs could be used as contrast agents, but in a passive targeting approach. Modifications to surface chemistry are required to target αVß6 integrin through active targeting. This study also highlights the need for controls such as scrambled peptides, the absence of which can lead to misinterpretation of results.

[French national standard for the treatment of squamous cell carcinoma of upper aero-digestive tract - General principles of treatment]. / Référentiel national de traitement des carcinomes épidermoïdes des voies aérodigestives supérieures ­ Principes généraux de traitement.

OBJECTIVES: The management of upper aerodigestive tract cancers is a complex specialty. It is essential to provide an update to establish optimal care. At the initiative of the INCa and under the auspices of the SFORL, the scientific committee, led by Professor Béatrix Barry, Dr. Gilles Dolivet, and Dr. Dominique De Raucourt, decided to develop a reference framework aimed at defining, in a scientific and consensus-based manner, the general principles of treatment for upper aerodigestive tract cancers applicable to all sub-locations. METHODOLOGY: To develop this framework, a multidisciplinary team of practitioners was formed. A systematic analysis of the literature was conducted to produce recommendations classified by grades, in accordance with the standards of the French National Authority for Health (HAS). RESULTS: The grading of recommendations according to HAS standards has allowed the establishment of a reference for patient care based on several criteria. In this framework, patients benefit from differentiated care based on prognostic factors they present (age, comorbidities, TNM status, HPV status, etc.), conditions of implementation, and quality criteria for indicated surgery (operability, resectability, margin quality, mutilation, salvage surgery), as well as quality criteria for radiotherapy (target volume, implementation time, etc.). The role of medical and postoperative treatments was also evaluated based on specific criteria. Finally, supportive care must be organized from the beginning and throughout the patients' care journey. CONCLUSION: All collected data have led to the development of a comprehensive framework aimed at harmonizing practices nationally, facilitating decision-making in multidisciplinary consultation meetings, promoting equality in practices, and providing a state-of-the-art and reference practices for assessing the quality of care. This new framework is intended to be updated every 5 years to best reflect the latest advances in the field.

Current Approaches to Salvage Surgery for Head and Neck Cancer: A Comprehensive Review.

Salvage surgeries of head and neck cancer are often complicated and do not always show decent results. This type of procedure is tough on the patient, as many crucial organs can be affected. A long period of reeducation usually follows the surgery because of the need to rehabilitate functions such as speech or swallowing. In order to lighten the journey of the patients, it is important to develop new technologies and techniques to ease the surgery and limit its damages. This seems even more crucial since progress has been made in the past years, allowing more salvage therapy to take place. This article aims at showing the available tools and procedures for salvage surgeries, such as transoral robotic surgery, free-flap surgery, sentinel node mapping, and many others, that help the work of the medical team to operate or obtain a better understanding of the status of the cancer when taken in charge. Yet, the surgical procedure is not the only thing determining the outcome of the operation. The patient themself and their cancer history also play an important part in the care and must be acknowledged.

Randomized phase II study of preoperative afatinib in untreated head and neck cancers: predictive and pharmacodynamic biomarkers of activity.

There is no strong and reliable predictive biomarker in head and neck squamous cell carcinoma (HNSCC) for EGFR inhibitors. We aimed to identify predictive and pharmacodynamic biomarkers of efficacy of afatinib, a pan-HER tyrosine kinase inhibitor, in a window-of-opportunity trial (NCT01415674). Multi-omics analyses were carried out on pre-treatment biopsy and surgical specimen for biological assessment of afatinib activity. Sixty-one treatment-naïve and operable HNSCC patients were randomised to afatinib 40 mg/day for 21-28 days versus no treatment. Afatinib produced a high rate of metabolic response. Responders had a higher expression of pERK1/2 (P = 0.02) and lower expressions of pHER4 (P = 0.03) and pRB1 (P = 0.002) in pre-treatment biopsy compared to non-responders. At the cellular level, responders displayed an enrichment of tumor-infiltrating B cells under afatinib (P = 0.02). At the molecular level, NF-kappa B signaling was over-represented among upregulated genes in non-responders (P < 0.001; FDR = 0.01). Although exploratory, phosphoproteomics-based biomarkers deserve further investigations as predictors of afatinib efficacy.

The musculocutaneous infrahyoid flap: surgical key points.

For the first time in 1979, it was described by Wang that the infrahyoid musculocutaneous flap (IHMC flap) appears to be extremely suitable for medium-sized head and neck defect. Nevertheless, this flap remains unpopular because of its pretended lack of reliability. The aim of this study is to describe the surgical key points and to expose its main advantages. An IHMC flap was achieved on 32 patients to repair tissue loss due to surgical resection of a squamous cell carcinoma of the upper aero-digestive tract, from March 2006 to January 2010. Medical records of each of these patients were retrospectively analysed by the investigators including the detailed clinical, pathological and operative reports. No patient presented with total flap necrosis. However, we experienced four skin paddles necrosis. In two cases, the necrosis was total and in two cases partial. All donor sites were closed primarily without any tension. One patient showed a major dehiscence of the neck skin incision that required a pectoralis major flap. The IHMC flap is reliable and the harvesting technique is simple when the surgical key points are respected. Its advantages make it a convenient flap for medium-sized head and neck defect.

Sentinel lymph node biopsy in patients with conjunctival and eyelid cancers: experience in 17 patients.

PURPOSE: To assess lymph node invasion through the use of sentinel lymph node biopsy (SLNB) in conjunctival and eyelid tumor patients and ascertain the impact of this technique in therapeutic management recommended by the multidisciplinary consensus committee. METHODS: A single center prospective nonrandomized clinical study was conducted between January 2008 and January 2010. Seventeen patients were included: 4 (2 conjunctiva and 2 eyelid) melanomas, 4 eyelid Merkel cell tumors, 8 (2 conjunctiva, 2 eyelid, 2 eyelid and conjunctiva, 2 cornea and conjunctiva) squamous cell tumors, and 1 eyelid meibomian carcinoma. Preoperative lymphoscintigraphy was done the day before surgery to label lymph node(s). The surgical biopsy was then performed along with an extemporaneous pathological examination followed by secondary complete lymph node dissection only in instances of positive histology. RESULTS: In all cases, one or more sentinel lymph nodes were identified (3-13). Two biopsies (1 Merkel cell carcinoma and 1 squamous cell carcinoma) revealed neoplastic invasion and led to complete cervical node dissection. Adjunct regional treatment was indicated for 1 melanoma, for 4 Merkel cell tumors, and for 2 squamous cell carcinomas. One false negative result was noted in the group of squamous cell carcinomas after 6 months, and it was treated. No relapse or death was observed for the other 16 patients. The mean overall follow-up was 18.2 months. CONCLUSION: As in previous studies, we found that SLNB for eyelid and conjunctival tumors is safe and effective in identifying microscopically positive SLNs. This procedure may also revive interest in the study of cervicofacial lymphatic drainage. Our current investigation is to be expanded and extended to other medical teams.

Feasibility of treating irradiated bone with intramedullary delivered autologous mesenchymal stem cells.

BACKGROUND: We aimed to explore (i) the short-term retention of intramedullary implanted mesenchymal stem cells BMSCs and (ii) their impact on the bone blood flow and metabolism in a rat model of hindlimb irradiation. METHODS: Three months after 30 Gy irradiation, fourteen animals were referred into 2 groups: a sham-operated group (n = 6) and a treated group (n = 8) in which ¹¹¹In-labelled BMSCs (2 × 106 cells) were injected in irradiated tibias. Bone blood flow and metabolism were assessed by serial (99m)Tc-HDP scintigraphy and 1-wk cell retention by recordings of (99m)Tc/¹¹¹In activities. RESULTS: The amount of intramedullary implanted BMSCs was of 70% at 2 H, 40% at 48 H, and 38% at 168 H. Bone blood flow and bone metabolism were significantly increased during the first week after cell transplantation, but these effects were found to reduce at 2-mo followup. Conclusion. Short-term cell retention produced concomitant enhancement in irradiated bone blood flow and metabolism.

[Surgical de-escalation for head and neck cancer surgery]. / Désescalade en chirurgie oncologique cervico-faciale.

Head and neck cancer surgery often has functional and aesthetic consequences. De-escalation surgery is a major concern for surgeons with a constant desire to develop surgical techniques with less invasive approaches and to preserve anatomical structures as much as possible. This was made possible by the appearance of minimally transoral and endonasal surgery as well as by the limitation of the surgical procedure by neoadjuvant treatments or by the limitation of surgical excision without compromising the oncological outcome and patient survival. This evolution continues with the arrival of new technologies such as virtual reality or artificial intelligence.

A Comparison of the Clinical and Radiological Extent of Denosumab (Xgeva®) Related Osteonecrosis of the Jaw: A Retrospective Study.

Medication-related osteonecrosis of the jaw (MRONJ) is a severe side effect of antiresorptive medication. The aim of this study was to evaluate the incidence of denosumab-related osteonecrosis of the jaw and to compare the clinical and radiological extent of osteonecrosis. A retrospective study of patients who received Xgeva® at the Institut de Cancérologie de Lorraine (ICL) was performed. Patients for whom clinical and radiological (CBCT) data were available were divided into two groups: "exposed" for patients with bone exposure and "fistula" when only a fistula through which the bone could be probed was observed. The difference between clinical and radiological extent was assessed. The p-value was set at 0.05, and a total of 246 patients were included. The cumulative incidence of osteonecrosis was 0.9% at 6 months, 7% at 12 months, and 15% from 24 months. The clinical extent of MRONJ was significantly less than their radiological extent: in the "exposed" group, 17 areas (45%) were less extensive clinically than radiologically (p < 0.001) and respectively 6 (67%) for the "fistula" group (p < 0.031). It would seem that a CBCT is essential to know the real extent of MRONJ. Thus, it would seem interesting to systematically perform a CBCT during the diagnosis of MRONJ, exploring the entire affected dental arch.

Estimating the risks and benefits before salvage surgery for recurrent head and neck squamous cell carcinoma.

INTRODUCTION: The risks associated with salvage surgery of head and neck squamous cell carcinoma (SCC) in a previously irradiated field needs to be balanced against the expected survival benefits. We want to identify preoperative predictive factors for overall and disease-specific survival (OS/DSS) and for the development of serious (Clavien-Dindo, CD≥III) complications following salvage surgery for radiorecurrent SCC to help surgeons, patients, and caregivers in the decision-making process in this setting. MATERIALS AND METHODS: The records of 234 patients presenting to the Lorraine Cancer Institute with locoregional radiorecurrent SCC were reviewed. The primary endpoint was OS, secondary endpoints were DSS, OS without tracheostomy/gastrostomy, and the risk of CD≥III complications. Multivariate analyses were carried out to explore preoperative factors associated with survival and the risk of postoperative complications. RESULTS: With a median follow-up time of 19 months, 5-year OS since the first salvage surgery was 28.3%, 5-year DSS was 38.9%. 2- and 5-year functional OS were 45.6% and 27.2%. rcT-rcN, and WUNHCI ≥4 were both independent significant preoperative predictors of OS and DSS. 30-days postoperative complications occurred in 44.4% of patients (28 CD I, 24 CD II, 34 CD III, 11 CD IV, 7 CD V). A salvage procedure involving T+N plus the presence of a WUHNCI ≥4 was the only independent predictor of CD≥III complications. CONCLUSION: When discussing with the patients and the caregivers salvage surgery for recurrent head and neck SCC, a careful evaluation of the preoperative comorbidities by the WUHNCI tool can reliably predict the expected risks and benefits from the procedure.

Expression of immune response biomarkers (PD­L1, p16, CD3+ and CD8+ TILs) in recurrent head and neck squamous cell carcinoma within previously irradiated areas.

The immune landscape of head and neck squamous cell carcinoma in pretreated areas remains poorly documented. We aimed to assess the tumor microenvironment for biomarkers of antitumor immune responses in tumors in previously irradiated areas compared with de novo tumors. This retrospective monocentric study analyzed 100 paraffin­embedded surgical samples of invasive head and neck squamous cell carcinoma (oral cavity, oropharynx, larynx, hypopharynx) from patients who underwent surgery between January 2010 and November 2017. We compared the immune microenvironment in 50 de novo tumors and 50 tumors recurring within irradiated areas. We used immunohistochemistry to assess p16 status, CD3+/CD8+ tumor­infiltrating lymphocytes (TILs), and programmed death­ligand 1 (PD­L1) expression on tumor and immune cells in stromal and intratumoral components. CD3+ TIL counts were significantly lower in intratumoral and stromal components (P=0.003 and P=0.020, respectively) in the irradiated area cohort; there was no significant difference between CD8+ TIL counts in the two cohorts. The percentage of tumors with PD­L1+ tumor cells (tumor proportion score ≥1%) was significantly lower within the irradiated area cohort than the de novo cohort (56.0% vs. 86.0%, P<0.001). There were also significantly fewer tumors with PD­L1+ immune cells in the irradiated area cohort. Predominantly, tumors from the irradiated area cohort had microenvironments classified as 'adaptive immune resistance'. There was persistence of cytotoxic cells in tumors in the irradiated areas but lower PD­L1 expression and CD3+ TIL counts than in the de novo tumors. This offers an initial hypothesis to explain why these lesions are less responsive to immunotherapy, even though they may still have antitumor capacities. Assessment of immune response biomarkers in patients treated with immunotherapy in randomized trials is required.

A NGS-based Blood Test For the Diagnosis of Invasive HPV-associated Carcinomas with Extensive Viral Genomic Characterization.

PURPOSE: Use of circulating tumor DNA (ctDNA) for diagnosis is limited regarding the low number of target molecules in early-stage tumors. Human papillomavirus (HPV)-associated carcinomas represent a privileged model using circulating viral DNA (ctHPV DNA) as a tumor marker. However, the plurality of HPV genotypes represents a challenge. The next-generation sequencing (NGS)-based CaptHPV approach is able to characterize any HPV DNA sequence. To assess the ability of this method to establish the diagnosis of HPV-associated cancer via a blood sample, we analyzed ctHPV DNA in HPV-positive or HPV-negative carcinomas. EXPERIMENTAL DESIGN: Patients (135) from France and Senegal with carcinoma developed in the uterine cervix (74), oropharynx (25), oral cavity (19), anus (12), and vulva (5) were prospectively registered. Matched tumor tissue and blood samples (10 mL) were taken before treatment and independently analyzed using the CaptHPV method. RESULTS: HPV prevalence in tumors was 60.0% (81/135; 15 different genotypes). Viral analysis of plasmas compared with tumors was available for 134 patients. In the group of 80 patients with HPV-positive tumors, 77 were also positive in plasma (sensitivity 95.0%); in the group of 54 patients with HPV-negative tumors, one was positive in plasma (specificity 98.1%). In most cases, the complete HPV pattern observed in tumors could be established from the analysis of ctHPV DNA. CONCLUSIONS: In patients with carcinoma associated with any HPV genotype, a complete viral genome characterization can be obtained via the analysis of a standard blood sample. This should favor the development of noninvasive diagnostic tests providing the identification of personalized tumor markers. See related commentary by Rostami et al., p. 5158.