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.

[PET in head and neck cancers]. / La TEP dans les cancers des voies aérodigestives supérieures.

FDG PET is useful when cancer in the head or neck (except for tumors of the salivary glands, which cannot be characterized accurately) is diagnosed or suspected but not confirmed by biopsy. It can, for example, find evidence of suspicious lymph nodes in clinically N0 necks, detect foci suggestive of distant metastases or second cancers, and provide useful prognostic information. Because it can be very difficult to identify anatomical structures and landmarks on PET images in the head and neck region, PET/CT fusion is very helpful in this area. In early assessment of chemotherapy, the absence of a significant reduction in FDG uptake after one or two cycles predicts lack of efficacy and thus indicates the need to modify the regimen. Conversely, the disappearance of FDG foci indicates effective treatment and good prognosis but cannot rule out the persistence of any malignant tissue at the end of treatment, especially neoadjuvant. Diagnostic impact is probably greatest in monitoring for recurrence and restaging known recurrence: FDG PET should be performed - perhaps routinely - early enough that curative options are still open, but long enough after the end of treatment to avoid false positive results from inflammation. The strategy and timing of FDG PET during follow-up should be determined in more detail in the future, as should the role (if any) of fluorotyrosine (FET) PET in squamous cell carcinoma.

[FDG-PET in localization of cancers of unknown primary origin]. / Place de la TEP au FDG dans la localisation des cancers de primitif inconnu.

FDG-PET can be successful in localizing the primary cancer when a metastasis is discovered but no primary tumor can be identified (cancer of unknown primary, or CUP) by physical examination, laboratory testing (for tumor markers, for example) or conventional imaging. The greatest number of PET studies in CUP concern secondary lesions in cervical lymph nodes, and PET is an established clinical use (highest ranking, 1A) according to the 3rd German Consensus Conference and an "option" in the French Standards, Options, and Recommendations. Success rates range from 30% to 50% in most studies using PET; a higher rate was reported recently with PET/CT. FDG-PET should be performed sufficiently early in cases of neurological paraneoplastic syndrome, because established lesions become irreversible. Identification of the antibody present helps to specify the organ and FDG-PET can then localize the lesion; together these techniques make it possible to perform curative surgery even when the primary tumor is not visible. The success rate is somewhat lower than in cases of metastasis, around 35%. The clinical utility of PET in other paraneoplastic syndromes has not yet been sufficiently studied, but these conditions are rare. It is precisely in cases with a kind of 'orphan' indication that FDG PET should be considered, as an effective "problem solver".

[PET in thyroid cancers]. / La TEP dans le cancer de la glande thyroïde.

FDG PET can detect thyroid cancer in patients referred for exploration of a different cancer. Because of its lack of specificity, however, this modality is not indicated for examination of thyroid nodules: ultrasonography and fine needle biopsy with cytology allow histological diagnosis, which can be completed by iodine-123 scintigraphy when an autonomous nodule is suspected. No information is currently available about the utility of FDG PET in preoperative staging. In follow-up of patients undergoing thyroidectomy for adenocarcinoma, FDG PET is useful for detecting recurrence in cases where serum thyroglobulin levels rise and iodine-131 scintigraphy is negative: surgical resection may be appropriate. Nonetheless FDG PET should be performed more widely and earlier: the initial presence of foci positive for FDG is a major predictor of shorter survival, and most cancer lesions take up either iodine or FDG. In follow-up of medullary carcinoma, FDG PET detects residual tissue better than any other scintigraphic procedures, especially when serum levels of CEA (carcinoembryonic antigen) are rising rapidly. FDOPA PET seems to have better sensitivity than FDG-PET and may be useful in occult recurrence, as three case reports indicate.

PABPN1 (GCN)11 as a Dominant Allele in Oculopharyngeal Muscular Dystrophy -Consequences in Clinical Diagnosis and Genetic Counselling.

Oculopharyngeal muscular dystrophy (OPMD) is mainly characterized by ptosis and dysphagia. The genetic cause is a short expansion of a (GCN)10 repeat encoding for polyalanine in the poly(A) binding protein nuclear 1 (PABPN1) gene to (GCN)12-17 repeats. The (GCN)11/Ala11 allele has so far been described to be either a polymorphism or a recessive allele with no effect on the phenotype in the heterozygous state. Here we report the clinical and histopathological phenotype of a patient carrying a single (GCN)11/Ala11 heterozygous allele and presenting an atypical form of OPMD with dysphagia and late and mild oculomotor symptoms. Intranuclear inclusions were observed in his muscle biopsy. This suggests a dominant mode of expression of the (GCN)11/Ala11 allele associated with a partial penetrance of OPMD.