Haïtham Mirghani

Treatment de-escalation in HPV-positive oropharyngeal carcinoma: Ongoing trials, critical issues and perspectives

Due to the generally poor prognosis of head and neck squamous cell carcinoma (HNSCC), treatment has been intensified, these last decades, leading to an increase of serious side effects. High‐risk human papillomavirus (HR‐HPV) infection has been recently etiologically linked to a subset of oropharyngeal squamous cell carcinoma (OPSCC), which is on the increase. These tumors are different, at the clinical and molecular level, when compared to tumors caused by traditional risk factors. Additionally, their prognosis is much more favorable which has led the medical community to consider new treatment strategies. Indeed, it is possible that less intensive treatment regimens could achieve similar efficacy with less toxicity and improved quality of life. Several clinical trials, investigating different ways to de‐escalate treatment, are currently ongoing. In this article, we review these main approaches, discuss the rationale behind them and the issues raised by treatment de‐escalation in HPV‐positive OPSCC.

Postradioiodine treatment whole-body scan in the era of 18-fluorodeoxyglucose positron emission tomography for differentiated thyroid carcinoma with elevated serum thyroglobulin levels.

BACKGROUNDnPatients with differentiated thyroid cancer (DTC) who have a suspicious recurrent or persistent disease based on an elevated serum thyroglobulin (Tg) or Tg antibodies (TgAb) are usually referred for empiric radioiodine ((131)I) administration to localize and treat the disease. The aim of this retrospective monocentric study was to assess the sensitivity of postempiric (131)I whole-body scan (WBS) compared to 18-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in such patients who had an initial normal postablation WBS.nnnMETHODSnAmong 47 consecutive patients with DTC who had a normal postablation WBS and were referred for empiric (131)I administration, 34 patients (12M, 22F; mean age 53 years) underwent FDG PET/CT and form the basis of this report: 23 patients had persistently elevated serum Tg levels, 10 had elevated Tg levels observed during follow-up after they initially became under 1 ng/mL, and 1 had appearance of TgAb during follow-up. Postempiric (131)I WBS and FDG PET/CT were analyzed by independent readers.nnnRESULTSnA total of 75 lesions were found in 23 patients, distributed in 36 organs. Lesions were located in the neck (30), lungs (28), mediastinum (11), and bones (6). The sensitivities for the detection of individual lesions and for the diagnosis of metastatic organs were 88% and 97% for PET/CT and 16% and 22% for WBS, respectively (p<0.01). PET/CT was abnormal in 22 patients, among which 5 also had an abnormal postempiric (131)I WBS. There was only one patient with an abnormal postempiric (131)I WBS and a normal FDG PET/CT. This patient underwent two further (131)I administrations, with the last WBS being normal and the last stimulated Tg level being undetectable. Other patients were either treated with surgery, or classified as radioactive iodine refractory and treated with levothyroxine suppressive therapy or tyrosine kinase inhibitors.nnnCONCLUSIONnIn patients with suspicious recurrence based on the Tg level after a normal postablation WBS, FDG PET/CT is the preferred scintigraphic method to localize disease rather than postempiric (131)I WBS. Empiric (131)I administration may be used only in patients who do not have a significant FDG uptake.

Influence of Prophylactic Neck Dissection on Rate of Retreatment for Papillary Thyroid Carcinoma

BackgroundProphylactic neck dissection (PND) for papillary thyroid cancer is controversial. The objective of this study was to analyze the influence of PND on the rate of retreatment.MethodsIn this retrospective case-control study, papillary thyroid carcinomas >10xa0mm without ultrasonographic evidence of nodal disease (cN0) were treated with total thyroidectomy (TT) or TT with bilateral central compartment PND. All received postoperative radioactive iodine (131I) and were followed for at least 1xa0year. We compared the rate of retreatment (surgery or 131I).ResultsAltogether, 246 patients (mean age 46xa0years, 78xa0% women) underwent TT (nxa0=xa091) or TTxa0+xa0PND (nxa0=xa0155). The groups were similar in age, sex, tumor size, and follow-up (median 6.3xa0years) (pxa0>xa00.05). Overall, 11 (12xa0%) of the patients in the TT group underwent reoperation in the central compartment for recurrence versus 3 (2xa0%) in the TTxa0+xa0PND group (pxa0<xa00.001). There were 1.18 administrations of 131I for the TT group versus 1.08 for the TTxa0+xa0PND group (pxa0=xa00.08). The average cumulative dose of 131I was 3.9xa0±xa01.8xa0GBq for the TT group and 3.8xa0±xa01.3xa0GBq for the TTxa0+xa0PND group (pxa0=xa00.52). Actuarial (Kaplan-Meier) 5-year retreatment rates were 14.7xa0% in the TT group and 6.5xa0% in the TTxa0+xa0PND group (pxa0=xa00.01, log-rank). The rate of permanent recurrent nerve paralysis was 2xa0% for the TT group and 1xa0% for the TTxa0+xa0PND group (pxa0=xa00.98). The rates of permanent hypoparathyroidism were 7 versus 3xa0%, respectively (pxa0=xa00.12).ConclusionsFive-year retreatment rates were lower in patients treated with PND, with no added permanent morbidity.

Do high-risk human papillomaviruses cause oral cavity squamous cell carcinoma?

High-risk human papillomaviruses (HR-HPV) are an established etiologic factor for a growing number of oropharyngeal cancers. However, their potential role in other upper aerodigestive tract locations is still a matter of debate, particularly in the oral cavity. This is of paramount importance as in the future diagnosis, treatment and follow up in head and neck squamous cell carcinoma may vary according to HPV status. This article reviews the recent published data and highlights some of the pitfalls that have hampered the accurate assessment of HR-HPV oncological role outside the oropharynx. We demonstrate that, in contrast to the oropharynx, only a small fraction of cancers located in the oral cavity seem to be HPV-related even in young non-smoking non-drinking patients. We emphasize several relevant factors to consider in assumed HPV-induced oral cavity cancers and discuss the current theories that explain why HPV-induced cancers arise preferentially in the oropharynx.

Oropharyngeal cancers: Relationship between epidermal growth factor receptor alterations and human papillomavirus status

High-risk human papillomavirus (HR-HPV), particularly type 16, is now recognised as a causative agent in a subset of oropharyngeal squamous cell carcinomas (OPSCCs). These tumours are on the increase and generally have a better prognosis than their HPV negative counterparts. This raises the question of de escalation therapy to reduce long term consequences in a younger cohort of patients with a long life expectancy. Several clinical trials with anti-epidermal growth factor receptor (EGFR) therapies, particularly cetuximab, are ongoing. Few data exist on the relationship between EGFR and HPV induced oropharyngeal cancers. We summarise the main studies in relation to EGFR alterations (gene copy number, protein expression and mutations) and the impact on prognosis of HPV positive tumours that express high levels of EGFR. We also discuss the opportunity of targeting this pathway in light of recent studies.

Voice quality after treatment of T1a glottic cancer

To compare voice handicap and quality of life after radiotherapy (RT) versus transoral laser surgery (LS) for T1a glottic carcinoma.

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

PURPOSEnHPV-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.nnnMATERIALS AND METHODSnp16-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.nnnRESULTSnTwenty-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).nnnCONCLUSIONSnCertain 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.

Sinonasal cancer: Analysis of oncological failures in 156 consecutive cases.

Sinonasal cancers are rare and associated with a poor prognosis. The purpose of this study was to report our experience and analyze the risk factors for oncologic failures.

Nodal recurrence of sinonasal cancer: Does the risk of cervical relapse justify a prophylactic neck treatment?

BACKGROUNDnSinonasal cancers are rare and no high-level evidence exists to determine their optimal management. Prophylactic neck treatment issue remains controversial. The aim of this study was to analyze the pattern of neck failure and to identify any prognostic factors that may influence neck control.nnnMETHODSnA retrospective review of 155 consecutive patients treated for sinonasal malignancy, without prophylactic neck treatment, between 1995 and 2005 at tertiary cancer center was performed. Demographic, clinical, morphological and pathological parameters were correlated with oncologic outcomes.nnnRESULTSnEight out of 155 patients (5%) presented initially with neck node metastasis. Complete remission was obtained for 133 patients after treatment completion. During follow up, 16 out of 133 patients (12%) were affected with regional recurrence. Neck failure occurred in 8 out of 51 patients with local failure and in 8 out of 82 patients locally controlled. Isolated nodal failure was observed in 5 patients initially cN0 out of 133 (3.8%) representing 7.3% of all recurrences and 3 of them underwent successful salvage therapy. None of the tested factors were significantly associated with neck control (p>0.05). Lymph node at diagnosis time was significantly and independently associated with poor survival (p=0.0012).nnnCONCLUSIONnIsolated neck relapse, when local control is achieved, is rare and salvage treatment is effective. Routine prophylactic neck treatment has little interest. However, this approach could be profitable to few selected patients, who remain to be defined. Further investigations are needed.

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.