HPV circulating tumoral DNA quantification by droplet-based digital PCR: A promising predictive and prognostic biomarker for HPV-associated oropharyngeal cancers.

We aimed to determine whether pretherapeutic assessment of HPV circulating tumoral DNA (HPV ctDNA) by droplet-based digital PCR (ddPCR) could constitute a predictive and prognostic biomarker for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). A mono-institutional prospective biomarker study on 66 patients with p16+/HPV16-positive oropharyngeal squamous cell carcinoma (OPSCC) was conducted in European Georges Pompidou Hospital, Paris, France. Blood samples were collected at the time of diagnosis before any treatment. Optimized digital PCR assays were used to quantify HPV16 ctDNA. Forty-seven (71%) patients showed a positive pretherapeutic HPV ctDNA at time of diagnosis. Interestingly, the quantity of HPV16 ctDNA at baseline, as assessed by ddPCR, was significantly correlated with the T/N/M status or OPSCC stages according to the 2018 new staging criteria for high-risk human papillomavirus (HR HPV) related OPSCC from American Joint Committee on Cancer (AJCC). Moreover, all recurrences and the majority (83%) of death reported events occurred in patients with positive HPV16 ctDNA at baseline. Finally, when posttreatment blood samples were available (n = 6), the kinetic of pretreatment/posttreatment HPV16 ctDNA was clearly associated with treatment success or failure. HPV ctDNA monitoring by ddPCR could constitute a useful and noninvasive dynamic biomarker to select HR HPV-related OPSCC patients eligible for potential treatment de-escalation and to monitor treatment response.

[Nasal polyposis]. / Polypose nasosinusienne.

Nasal Polyposis. Nasal polyposis is a chronic bilateral rhinosinusitis characterized by the development of polyps in the nasal cavities whose prevalence is estimated in the general population at about 5%. The semiology is dominated by nasal obstruction, posterior rhinorrhea and anosmia. The Widal-Samster triad associates nasal polyposis, asthma, and intolerance to aspirin, sulfites, and NSAIDs. The treatment is medical; it is based on long-term local corticosteroid therapy, and general corticosteroid therapy not exceeding three short annual courses. Surgery was only performed when failures of medical treatment; it is performed by endonasal videosurgery when patients remain uncomfortable with significant symptoms despite the use of at least three short courses of oral corticosteroids per year.

Polypose nasosinusienne. La polypose nasosinusienne est une rhinosinusite chronique bilatérale caractérisée par le développement de polypes dans les cavités nasosinusiennes. Sa prévalence est estimée dans la population générale à environ 5 %. La sémiologie est dominée par l'obstruction nasale, la rhinorrhée postérieure et l'anosmie. Elle est soit isolée, soit associée dans le cadre du syndrome de Widal à un asthme et à une intolérance à l'aspirine, aux sulfites et aux anti-inflammatoires non stéroïdiens. Le traitement est d'abord médical, qui repose sur la corticothérapie locale au long cours, et générale en ne dépassant pas trois cures courtes par an. La chirurgie n'existe qu'en raison des échecs du traitement médical ; elle est réalisée par vidéochirurgie endonasale.

HPV RNA CISH score identifies two prognostic groups in a p16 positive oropharyngeal squamous cell carcinoma population.

HPV-related and HPV-unrelated oropharyngeal squamous cell carcinomas are two distinct entities according to the Union for International Cancer Control, with a better prognosis conferred to HPV-related oropharyngeal squamous cell carcinomas. However, variable clinical outcomes are observed among patients with p16 positive oropharyngeal squamous cell carcinoma, which is a surrogate marker of HPV infection. We aimed to investigate the prognostic value of RNA CISH against E6 and E7 transcripts (HPV RNA CISH) to predict such variability. We retrospectively included 50 histologically confirmed p16 positive oropharyngeal squamous cell carcinomas (p16 positive immunostaining was defined by a strong staining in 70% or more of tumor cells). HPV RNA CISH staining was assessed semi-quantitatively to define two scores: RNA CISH "low" and RNA CISH "high". Negative HPV RNA CISH cases were scored as RNA CISH "low". This series contained 29 RNA CISH low cases (58%) and 21 RNA CISH high cases (42%). Clinical and pathologic baseline characteristics were similar between the two groups. RNA CISH high staining was associated with a better overall survival in both univariate and multivariate analyses (p = 0.033 and p = 0.042, respectively). Other recorded parameters had no prognostic value. In conclusion, HPV RNA CISH might be an independent prognostic marker in p16 positive oropharyngeal squamous cell carcinomas and might help guide therapeutics.

PCR-based detection of Aspergillus fumigatus and absence of azole resistance due to TR34 /L98H in a french multicenter cohort of 137 patients with fungal rhinosinusitis.

Fungal rhinosinusitis (FRS) has a worldwide distribution, comprises distinct clinical entities but is mostly due to Aspergillus among which Aspergillus fumigatus plays a major role in European countries. Although, there is accumulating evidence for the emergence of environmentally acquired-azole resistance in A. fumigatus (such as TR34 /L98H) in various clinical settings, there is few data for patients with FRS. In this study, we aimed to investigate the prevalence of A. fumigatus azole resistance due to TR34 /L98H in a multicentre cohort of patients with FRS. One hundred and thirty-seven patients with FRS admitted between 2002 and 2016 at four French medical centres were retrospectively enrolled. Clinical and mycological findings were collected. Aspergillus fumigatus and the TR34 /L98H alteration conferring azole resistance were investigated directly from clinical samples using the commercial CE-IVD marked MycoGENIE® A. fumigatus real-time PCR assay. Fungal ball was the more frequent clinical form (n = 118). Despite the presence of fungal hyphae at direct microscopic examination, mycological cultures remained negative for 83 out of the 137 patients (60.6%). The PCR assay proved to be useful allowing the identification of A. fumigatus and etiological diagnosis in 106 patients (77.4%) compared with 44 patients (32.1%) when using culture as the reference method. Importantly, neither TR34 nor L98H alterations were evidenced.

Postoperative hemorrhage after transoral oropharyngectomy for cancer of the lateral oropharynx.

OBJECTIVE: Assessment of incidence, risk factors, management, and outcome of postoperative hemorrhage after transoral oropharyngectomy for cancer of the lateral oropharynx. METHODS: Retrospective review of a cohort of 514 cancers of the lateral oropharynx consecutively resected. RESULTS: Incidence of postoperative hemorrhage was 3.6%. In 31.5% of cases, onset was after hospital discharge. No hemorrhages occurred after the end of the fourth postoperative week. Variables associated with increased risk of hemorrhage were advanced age (P=.004), antithrombotic treatment (P=.012), and robotic assistance (P=.009). When the source of hemorrhage could be identified, hemostasis, performed transorally in most cases, was highly effective; no patients in this subgroup showed recurrence. In spontaneously resolved hemorrhage under observation or when no active site of bleeding was found on exploration under general anesthesia, the recurrence rate was 18.1%. Overall, hemorrhage resulted in death in 2 patients. CONCLUSION: Exploration under general anesthesia in case of active bleeding and observation with discussion of arterial exploration of the ipsilateral external carotid system in patients in whom no source of bleeding can be identified are the keys to successful management of this potentially lethal complication.

[Olfaction: from nose to cortex]. / Odorat : de l'aéroportage au cortex.

Olfactory physiology involves four main steps: nasal airflow perireceptor events, transduction, and central olfaction. Complex and diverse physiological processes are involved at each step and may be undermined by numerous pathological processes. Nasal airflow physiology involves fluid mechanics and specifc physicochemical properties of odorants; its main pathology is nasal polyposis. Perireceptor events involve transport molecules and enzymes which eliminate xenobiotics; its main pathology is chronic rhinitis. Transduction is the role of primary olfactory neurons, which detect and discriminate various chemical molecules across a wide range of concentrations. To fulfill this task, these cells use a large family of G protein-coupled receptors (odorant receptors). The main pathology is acute viral rhinitis affecting the olfactory organ. Finally, after olfactory signals are generated, the information is processed and coded in the olfactory bulb before being disseminated to several areas of the brain; its pathology is dominated by neurodegenerative disorders.

Glottic bamboo nodules from systemic lupus erythematosus.

Bamboo nodules of the glottis are of late being described as a distinct entity seen in patients with autoimmune diseases. We report the symptoms, clinical features, and management of a case of bamboo nodules of the glottis in a patient with systemic lupus erythematosus. We discuss the pathogenesis and management of this condition on the basis of a review of the medical literature.

Trade-off between survival and laryngeal preservation in advanced laryngeal cancer: the otorhinolaryngology patient's perspective.

OBJECTIVES: We performed a prospective study to evaluate, from the patient's perspective, the trade-off between speech and survival that individuals face when given a diagnosis of advanced-stage laryngeal cancer amenable to either total laryngectomy or a laryngeal preservation protocol using chemotherapy and radiotherapy. METHODS: Volunteers (309) consecutively seen at the otorhinolaryngology clinic of a university teaching hospital in France completed an anonymous questionnaire designed to determine their position if they faced the diagnosis of an advanced-stage laryngeal cancer. Univariate analysis was performed for potential statistical relationships with various variables. RESULTS: We found that 12.9% of patients were unable to determine their position regarding the two treatment options offered, and this group had a significant statistical relationship with four variables (age, education, professional status, and history of cancer among relatives). We found that 24.6% of patients made survival their main consideration and would not consider any trade-off. Among the 62.5% who considered the trade-off, the percentage of cure that patients were ready to lose in order to preserve their larynx varied from 5% to 100% (mean, 33%; SD, 23%). Aside from the undecided group, none of the variables analyzed was related either to the decision as to whether to consider a trade-off or to the percentage of c re that patients agreed to trade to preserve their larynx. CONCLUSIONS: In patients with advanced-stage laryngeal cancer, treatment should be initiated only after careful evaluation of the patient's attitude toward both laryngeal preservation and survival.

[Unilateral laryngeal paralysis in the adult patient]. / Paralysies laryngées unilatérales de l'adulte.

Based on a review of the recent medical literature, the authors document the epidemiological evolution, pathophysisology diagnosis and recent advances in treatment for adult patients with unilateral laryngeal paralysis. Speech therapy, which used to be the only therapeutic option, is nowadays complemented by efficient surgical techniques, which have modified the management of many patients.

Analysis of Microbiota and Mycobiota in Fungal Ball Rhinosinusitis: Specific Interaction between Aspergillus fumigatus and Haemophilus influenza?

Fungal ball (FB) rhinosinusitis (RS) is the main type of non-invasive fungal RS. Despite positive direct examination (DE) of biopsies, culture remains negative in more than 60% of cases. The aim of the study was to evaluate the performance/efficacy of targeted metagenomics (TM) to analyze microbiota and mycobiota in FB and find microbial associations. Forty-five sinus biopsies from patients who underwent surgery for chronic RS were included. After DE and culture, DNA was extracted, then fungal ITS1-ITS2 and bacterial V3-V4 16S rDNA loci were sequenced (MiSeqTM Illumina). Operational taxonomic units (OTUs) were defined via QIIME and assigned to SILVA (16S) and UNITE (ITS) databases. Statistical analyses were performed using SHAMAN. Thirty-eight patients had FB and seven had non-fungal rhinosinusitis (NFRS). DE and culture of FB were positive for fungi in 97.3 and 31.6% of patients, respectively. TM analysis of the 38 FB yielded more than one fungal genus in 100% of cases, with Aspergillus in 89.5% (34/38). Haemophilus was over-represented in FB with >1000 reads/sample in 47.3% (18/38) compared to NFRS (p < 0.001). TM allowed fungal identification in biopsies with negative culture. Haemophilus was associated with FB. Pathogenesis could result from fungi-bacteria interactions in a mixed biofilm-like structure.

[Isolated unilateral laryngeal nerve paralysis in adults. An inception cohort of 591 patients managed in a French--university--teaching hospital]. / Paralysies laryngées unilatérales isolées de l'adulte: etude d'une cohorte de 591 patients pris en charge en centre hospitalo-universitaire.

UNLABELLED: We analyzed an inception cohort of 591 adults with isolated unilateral laryngeal paralysis managed at a French teaching hospital during the period 1990-2008. Symptoms, causes, treatment and outcome were compared between two periods (1990-2000 vs 2001-2008), using the Chi squared test and Mann Whitney U test. Dysphonia, swallowing impairment and respiratory impairment were present in respectively 98.3%, 34.8% and 4.1% of cases, The causes of paralysis were surgical and non surgical in respectively 65.1% and 21.1% of cases. Cancer (mainly lung cancer) was present in 59.6% of cases, and 22% of these patients were receiving palliative treatment. Thoraco-mediastinal surgery and thyroid-parathyroid surgery accounted for 79.4% of surgical causes. Malignancies accounted for 76.8% of non surgical causes. Within the idiopathic group (13.8% of the cohort), a tumor lying along the path of the paralyzed nerve was detected in 3.7% of cases. Larynx motion was recovered in 19.6% of cases; nerve transection, the etiology, and the time since symptom onset were predictive factors for motion recovery. Treatment consisted of laryngeal medialisation and isolated speech therapy in 40.1% and 59.9% of cases, respectively. The current success rate of laryngeal medialisation is 90.3%. CONCLUSIONS: The three main causes of unilateral laryngeal nerve paralysis were tumors, surgery and cardiovascular disorders (surgical and non surgical). Laryngeal medialisation is now a major component of rehabilitation in our center.

[Thyroid tumors in the adult revealed by unilateral laryngeal paralysis]. / Tumeurs thyroïdiennes de l'adulte révélées par une paralysie laryngée unilatérale.

GOAL: To analyze the characteristic of thyroid tumor associated with ipsilateral unilateral laryngeal paralysis (ULP) in the adult patient. MATERIALS AND METHODS: Retrospective analysis of a cohort of 30 patients with ULP related to an ipsilateral thyroid tumor (group A) and comparison with a cohort of 99 patients in whom ULP revealed a non-thyroid tumor (group B). RESULTS: Group A consisted of 66.6% of women with a mean age of 69 years. Comparison between both groups noted that female gender was more frequent in group A (66.6% vs. 17.1%, P<0.0001), and the underlying tumor was more frequently malignant in group B (89.9% vs. 43.4%, P<0.0001). Within group A, the incidence for recovery of laryngeal motion varied form 0% for malignant tumor to 50% for benign tumor. In patients with a benign thyroid tumor in whom recovery of laryngeal motion did not occur, the watch policy initiated allowed to detect a pathology (malignant tumor or neurological) explaining persistent ULP in 57% of cases. CONCLUSION: The present series confirm that ULP in the face of thyroid tumor does not allow to distinguish formally between benign and malignant tumors and highlight the value of a long term watch policy in patients with benign thyroid tumor pathology in whom recovery of laryngeal mobility does not occur.

HPV detection and genotyping of head and neck cancer biopsies by molecular testing with regard to the new oropharyngeal squamous cell carcinoma classification based on HPV status.

Recently, both the World Health Organization/International Agency for Research on Cancer (WHO/IARC) and the American Joint Committee on Cancer (AJCC) have classified oropharyngeal squamous cell carcinoma (OPSCC) on the basis of HPV status. For this purpose, the WHO/IARC recommended direct molecular HPV testing. In practice, formalin-fixed, paraffin-embedded (FFPE) biopsy specimens are frequently the only available samples. We herein compared in parallel two commercially available molecular assays that were first designed for cervical HPV detection and genotyping: Inno-Lipa HPV Genotyping Extra II (IL) and Anyplex II HPV28 (AP28). A total of 55 samples were tested. By IL assay, chosen as reference assay, 27 (49.1%) biopsies were positive for HPV16, 10 (18.2%) were positive for HPV but negative for HPV16, and 18 (32.7%) were negative for HPV. A valid result with AP28 was obtained for 51 biopsy samples (92.7%). Among 37 HPV positive samples by IL, 33 (89.2%) were positive by AP28. The agreement between both assays was good (Cohen's κ = 0.78). Among the six discrepancies between assays, always associated with low HPV16 viral load, four biopsies positive for HPV16 by IL could not be detected by AP28. Taken together, these observations demonstrate that both assays could be used in routine HPV detection and genotyping on FFPE biopsy samples of head and neck tumours.

Ten-year outcome of curative "exclusive" chemotherapy in N0M0 squamous cell carcinoma of the larynx and pharynx with complete clinical response.

BACKGROUND: The aim of our study was to document 10-year outcome after curative "exclusive" chemotherapy in N0M0 squamous cell carcinoma of the larynx and pharynx. METHODS: Retrospective nonrandomized analysis of an inception cohort of 191 patients. Platinum salt and 5-fluorouracil were used in all patients. RESULTS: The 3-, 5-, 10-year overall actuarial survival and local control estimates were 83.3%, 74.4%, and 55.4% and 62.1%, 62.1%, and 55.3%, respectively. Main causes of death were metachronous second primary cancer (n = 39) and intercurrent disease (n = 28). No clinical variables were associated with increased risk of local recurrence. Salvage treatment resulted in 94.7% ultimate local control and 88.4% organ preservation. "Exclusive" chemotherapy was considered "beneficial" in 62.3% and "detrimental" in 7.8% of cases. CONCLUSION: The high rate of local recurrence may be thought not to justify this treatment. Nevertheless, many patients avoided surgery and remained free of disease. Therefore, this approach deserves further study in the era of immune checkpoints inhibitors.

Influence of allergy in patients with nasal polyposis after endoscopic sinus surgery.

CONCLUSION: Allergy does not modify the symptoms and steroid consumption (oral and local) of nasal polyposis (NP) patients after functional endoscopic sinus surgery (FESS). OBJECTIVES: To assess the role of allergy in the evolution after FESS of patients presenting with the diagnosis of NP. PATIENTS AND METHODS: This was a prospective study of 63 consecutive patients with NP (57% males, mean age 45.8 years), who were analyzed to detect whether the results of a surgical treatment of NP were influenced by the presence of positive allergic tests (Phadiatop). Three nasal criteria were scored: nasal obstruction, posterior rhinorrhea, and the loss of smell. The frequency of asthma was evaluated. Medical treatment of NP after FESS consisted of washing of the nasal cavities, steroid spray, and oral steroid administration. The amount of consumption of steroids (prednisolone and beclomethasone) was studied. RESULTS: Decrease of all nasal symptoms was not statistically different in the two groups of patients with and without allergy. Cumulative consumption of prednisolone and beclomethasone after surgery was similar in the two groups.

Evaluation of combined medical and surgical treatment in nasal polyposis - III. Correlation between symptoms and CT scores before and after surgery for nasal polyposis.

CONCLUSION: Computed tomography (CT) in nasal polyposis (NP) patients has three functions before any treatment. CT provides objective evidence of the disease and precise topography of the disease, and is an indicator of the disease severity. After functional endoscopic sinus surgery (FESS), CT is an indicator of the residual disease severity and permits detection of asymptomatic mucoceles. OBJECTIVE: NP affects nearly 4% of the population. CT has become the examination of choice for the exploration of NP. FESS is accepted for NP treatment in the setting of failure of medical management. The aim of this study was to find out whether any correlation exists between symptom severity and CT scan score before and after FESS. PATIENTS AND METHODS: A total of 114 CT scans were performed in NP patients without contrast medium before and after FESS (mean follow-up 5 years), and were scored according to the Lund-MacKay system. RESULTS: Lund-MacKay scores before treatment ranged from 8 to 24. There was a correlation between symptom and CT scores before any treatment. Postoperative Lund-MacKay scores ranged from 0 to 24. There was a correlation between symptom and CT scores after surgery. There was no correlation between postoperative symptom and baseline CT scores. Eleven asymptomatic mucoceles were found.

Meningeal marginal zone B-cell lymphoma: The meningioma trap.

OBJECTIVE: To report a case of marginal zone MALT lymphoma of the temporal dura mater, initially mistaken for temporal meningioma. CASE REPORT: A 60-year-old immunocompetent woman, followed for more than 10 years for temporal meningioma causing vertigo and mixed hearing loss, presented with cervical lymphadenopathy, revealing marked progression of an intracranial lesion, leading to a diagnosis of marginal zone MALT lymphoma based on histological examination of a cervical lymph node. Treatment with 6 cycles of rituximab and bendamustine allowed complete remission of cervical lymph node and intracranial lesions, confirming the diagnosis of temporal dural mater lymphoma. CONCLUSION: Primary dural lymphoma must be part of the differential diagnosis of meningioma. Long-term follow-up allows correction of the diagnosis.

Mucocele development after endoscopic sinus surgery for nasal polyposis: A long-term analysis.

The aim of the present study was to determine the prevalence of long-term mucocele development after functional endoscopic sinus surgery (FESS) for nasal polyposis, to search for a statistical relationship with preoperative variables and to analyze the management of this complication. A retrospective analysis of 153 patients who underwent FESS for nasal polyposis, with a minimum of 7 years of follow-up, was performed. Mucocele diagnosis was based on regular clinical and radiologic evaluation. Univariate and multivariate statistical analysis was performed. The postoperative mucocele rate was 13.1% (20 patients). The mean delay between surgery and mucocele diagnosis was 6.25 years. A high preoperative Lund-Mackay score (>19) was a risk factor for postoperative mucocele (p = 0.04). Asthma and aspirin intolerance did not increase the risk of this complication. Endoscopic marsupialization of mucoceles was successful in 19 patients, with only one recurrent frontal mucocele. One patient required external approaches for two frontal mucoceles. In conclusion, mucocele risk after FESS for nasal polyposis is significant, especially in case of a high preoperative Lund-Mackay score (>19). Long-term clinical follow-up is recommended, imaging being prescribed based on symptoms or abnormal findings on clinical examination. Endoscopic marsupialization is very effective, but frontal mucoceles are more likely to recur.

Frontal sinus revision rate after nasal polyposis surgery including frontal recess clearance and middle turbinectomy: A long-term analysis.

OBJECTIVE: To determine the frontal sinus revision rate after nasal polyposis (NP) surgery including frontal recess clearance (FRC) and middle turbinectomy (MT), to search for predictive factors and to analyse surgical management. METHODS: Longitudinal analysis of 153 patients who consecutively underwent bilateral sphenoethmoidectomy with FRC and MT for NP with a minimum follow-up of 7 years. Decision of revision surgery was made in case of medically refractory chronic frontal sinusitis or frontal mucocele. Univariate and multivariate analysis incorporating clinical and radiological variables were performed. RESULTS: The frontal sinus revision rate was 6.5% (10/153). The mean time between the initial procedure and revision surgery was 3 years, 10 months. Osteitis around the frontal sinus outflow tract (FSOT) was associated with a higher risk of frontal sinus revision surgery (p=0.01). Asthma and aspirin intolerance did not increase the risk, as well as frontal sinus ostium diameter or residual frontoethmoid cells. Among revised patients, 60% required multiple procedures and 70% required frontal sinus ostium enlargement. CONCLUSIONS: Our long-term study reports that NP surgery including FRC and MT is associated with a low frontal sinus revision rate (6.5%). Patients developing osteitis around the FSOT have a higher risk of frontal sinus revision surgery. As mucosal damage can lead to osteitis, FSOT mucosa should be preserved during initial NP surgery. However, as multiple procedures are common among NP patients requiring frontal sinus revision, frontal sinus ostium enlargement should be considered during first revision in the hope of reducing the need of further revisions.

Evaluation of the efficacy of the 4 tests (p16 immunochemistry, polymerase chain reaction, DNA, and RNA in situ hybridization) to evaluate a human papillomavirus infection in head and neck cancers: a cohort of 348 French squamous cell carcinomas.

It is now established that human papillomavirus (HPV) plays a role in the development of a subset of head and neck squamous cell carcinomas (SCCs), notably oropharyngeal (OP) SCCs. However, it is not clear which test one should use to detect HPV in OP and non-OP SCCs. In this study, using 348 head and neck SCCs (126 OP SCCs and 222 non-OP SCCs), we evaluated diagnostic performances of different HPV tests in OP and non-OP SCCs: polymerase chain reaction, p16 immunostaining, in situ hybridization targeting DNA (DNA-CISH) and RNA (RNA-CISH), combined p16 + DNA-CISH, and combined p16 + RNA-CISH. HPV DNA (polymerase chain reaction) was detected in 26% of all tumors (44% of OP SCCs and 17% of non-OP SCCs). For OP SCCs, RNA-CISH was the most sensitive stand-alone test (88%), but p16 + RNA-CISH was even more sensitive (95%). Specificities were the same for RNA-CISH and DNA-CISH (97%), but it was better for p16 + RNA-CISH (100%). For non-OP SCCs, all tests had sensitivities less than 50%, and RNA-CISH, DNA-CISH, and p16 + DNA-CISH had 100%, 97%, and 99% specificities, respectively. As a stand-alone test, RNA-CISH is the most performant assay to detect HPV in OP SCCs, and combined p16 + RNA-CISH test slightly improves its performances. However, RNA-CISH has the advantage of being one single test. Like p16 and DNA-CISH, RNA-CISH performances are poor in non-OP SCCs to detect HPV, and combining tests does not improve performances.