7. Clinical diagnostics – Oropharyngeal and Hypopharyngeal Carcinoma

The clinical examination for suspected oropharyngeal or hypopharyngeal carcinoma includes specific ENT examinations following a general medical history, full body examination and recording of relevant comorbidities: This involves endoscopy of the oral cavity, oro- and hypopharynx and larynx in the phonation and respiratory position. A 90° magnifying laryngoscope should be used for this purpose, whereby surface anaesthesia of the pharynx usually improves the examination options. Many patients with malignancies of the head and neck have a considerable gag reflex, which makes indirect examination of the larynx, deep oropharynx and hypopharyngeal entrance via the oral cavity difficult or even impossible. In such cases, only a flexible endoscopic examination with a 4 mm flexible rhino-pharyngo-laryngoscope is possible, which is advanced via the lower nasal passage and the pharynx to the larynx after local surface anaesthesia. In addition to the assessment of pathological mucosal changes, particular attention must be paid to vocal fold mobility. A phoniatric examination to assess the vibration behaviour of the vocal folds, particularly in hypopharyngeal carcinomas with incipient vocal fold fixation with the aid of a stroboscope, is recommended.

Systemic tumour seeding, especially in the lungs, is also possible. If several regions of the pharynx and larynx are affected at the same time, this is referred to as multilocular tumour growth. For this reason and due to the possible presence of synchronous secondary carcinomas in the pharynx or larynx, endoscopy of the neighbouring mucosal areas, e.g. with a 90° loupe laryngoscope or with a flexible rhino-pharyngo-laryngoscope, is part of the primary clinical diagnosis of oropharyngeal and hypopharyngeal carcinoma. During panendoscopy under anaesthesia, the tracheo-bronchial system and the oesophagus can also be examined in order to rule out further secondary carcinomas and to determine the exact extent of the tumour by palpation and endoscopy while the patient is relaxed.

Suspect lesions distant from the primary tumour should be biopsied separately. In these situations, a mapping biopsy in inconspicuous areas of the mucosa may also be useful. The clinical examination also includes palpation of the neck to detect lymph node metastases, which is supplemented by ultrasound and CT/MRI if neoplasia is suspected. Newer endoscopic procedures such as coherence tomography, autofluorescence and electronic chromoendoscopy (narrow band imaging) can also be used.

In the context of the hitherto largely unstructured recording of the individual surgical risk or the individual stress limit with regard to therapeutic procedures to be performed, the systematic recording of comorbidities and so-called "frailty" (a state of reduced physical resistance after stress) has recently come to the fore. This is also related to the diversification of treatment options for head and neck cancer, which should of course be adapted to the individual conditions of a patient as part of a geriatric assessment with regard to undesirable treatment-related complications (adverse events). Patients older than 65 years make up the majority of cancer patients, which is why the group of older patients is particularly relevant and important for treatment in all oncological disciplines [Rostoft, S et al. 2021]. Therefore, assessment of frailty in elderly patients is recommended prior to surgical [138] or oncologic [139] therapy. On the other hand, increased symptom burden is an important risk factor for poor clinical outcomes [140] and the presence of mental health problems [141] in cancer patients as well. Established instruments such as the G8 questionnaire [142] or the ^MIDOS2 [143] are currently available. Initial validations of these instruments in collectives of patients with head and neck tumours show a significant correlation between frailty and increased symptom burden and thus indicate coherence in HNSCC patients, as these two risk factors can predict the presence of the other [144] [145] [146]. A deeper understanding of the coherence between these two risk factors could potentially facilitate the achievement of a better quality of life by reducing treatment-related complication rates.

The information in the literature regarding the superiority of CT or MRI for diagnosing the primary tumour in the oropharynx or hypopharynx is inconsistent. A number of authors consider MRI to be the method of choice due to its higher sensitivity; in other publications, CT is classified as better or at least equivalent [173] [174]. CT examinations are generally better tolerated by patients than MRI examinations due to the short examination time [162]. The better soft tissue contrast with higher detail recognition of soft tissues and superficial structures and, above all, the lower artifacts caused by metallic fillings or implants speak in favour of MRI [175]. While CT is occasionally considered advantageous for the assessment of cortical erosion, MRI provides a better depiction of perineural, intramuscular [162], or perivascular tumour extension as well as a more precise diagnosis of any involvement of the skull base, orbit or cervical spine [175]. It has been shown that CT is perceived as more comfortable than MRI due to the faster examination technique [162].

In a meta-analysis that included 2 studies focusing on T-stage, 1 study focusing on T- and N-stage and 3 studies focusing on N-stage, the pooled sensitivity/specificity was 89.3% / 89.5% (PET/CT) and 71.6% / 78.0% for conventional cross-sectional imaging (CT and MRI) ([176]).

CT and MRI are of similar accuracy for the diagnosis of cervical lymph node metastases; they are clearly superior to clinical examination [177]. CT appears to be slightly more reliable than MRI for the visualization of infrahyoid lymph node metastases, while the latter appears to visualize the nodes along the vascular nerve sheath better. MRI is therefore recommended for routine diagnostics to determine soft tissue infiltration and lymph node status [155]. In a direct comparative study, MRI performed better than CT for the determination of cervical lymph node metastases in terms of sensitivity, specificity and accuracy [160]. In combination with FDG-PET, the diagnostic accuracy of MRI can be increased [159], without, however, allowing a reliable statement to be made about the dignity of the detected lymph nodes [178] [172]. In principle, however, PET is much less informative as a stand-alone method than in combination with CT or MRI [179][159] [180] [181] and should therefore always be performed as a hybrid procedure (PET-CT or PET-MRI).

The accuracy of CT, MRI and ultrasound in the assessment of lymph node metastases is comparable, although the data on this is sparse. In the case of borderline large lymph nodes (short diameter > 5mm) on CT or MRI without signs of central necrosis, a targeted ultrasound-guided fine needle biopsy or FDG-PET can increase diagnostic accuracy [164] [165]. However, the value of PET-CT for the diagnosis of cervical lymph nodes is controversial due to the high number of false positive findings [153] [157] [182][183]. This method is considered particularly unsuitable for lymph nodes less than 10 mm in size [182][183].

In the 8th edition of the TNM classification, the determination of extranodal tumour growth (ENE, extranodal extension) was excluded in pretherapeutic staging for HPV16/p16-positive oropharyngeal carcinomas, but it remains highly valid for postoperative adjuvant therapy decisions. In a meta-analysis that included 2478 patients from 22 studies, the pooled sensitivity/specificity was 0.73/0.83 (CT) and 0.60/0.96 (MRI), with a lower pooled specificity for HPV-positive than for HPV-negative oropharyngeal cancers (0.74 vs. 0.87) [184]

A standard method for assessing the cervical lymph nodes is ultrasonography, for which a higher sensitivity and specificity have been reported in individual studies than for CT [185] or MRI [186]. It is an inexpensive method that can often be repeated during follow-up, but its accuracy and informative value depend heavily on the experience of the examiner. However, other studies indicate that the reliability of ultrasound staging of the neck is limited due to its low specificity [187].

Few studies have looked at the sensitivity of ultrasound-guided fine-needle biopsy (FNB) to determine pathologic lyphatic node dignity. While the sensitivity of this method is low for small tumours with a clinical N0 neck [188][189], it can be helpful for preoperative confirmation of dignity in palpable LKs. Ultrasound-guided fine-needle aspiration has a higher specificity than CT for palpable lumps [177], but no higher overall diagnostic reliability [163].

A combination of the examination modalities CT, MRI and PET-CT does not lead to any significant improvement [156]. Despite its high sensitivity, PET-CT has no improved diagnostic value for primary tumours and therefore cannot replace the established CT or MRI procedures [190][150] [151]. The meta-analysis published in 2008 by Kyzas et al. [157] included 32 studies on the diagnostic value of FDG-PET/CT in patients with a head and neck tumour. For cN0 patients, the sensitivity of FDG-PET alone was 50% (95% CI = 37-63%) and the specificity was 87% (95% CI = 76-93%). In studies with FDG-PET and anatomical imaging, the respective sensitivities and specificities were 80%/86% and 75%/79%, but not specified for cN0 patients.

In a further meta-analysis on the detection of distant metastases in advanced pharyngeal carcinoma, which summarized 1166 patients from 9 studies, the following pooled sensitivity/specificity was found: 0.92/0.93 (PET/CT + MRI), 0.80/0.91 (PET/MRI), 0.79/0.88 (PET/CT). Metastases were found in 9.2% and synchronous tumours in 11.8% of the cohort [191]

The higher the T category, the higher the probability of the presence of a secondary tumour or metastases in the lung, although secondary tumours or distant metastases may also be present in smaller tumours (especially in the hypopharynx) [192]. For this reason, a chest CT is generally recommended as part of the diagnosis of the primary tumour (chest X-ray overview is obsolete for staging) [166]. Both LK metastases and a second pulmonary carcinoma can be detected by CT with high sensitivity and specificity [167]. In patients with suspected recurrence in the head and neck region, sonography of the neck regions may also be indicated to justify the indication for further measures [193]. In comparison with bone scintigraphy and abdominal ultrasound, CT proved to be the safest screening method for detecting distant metastases [166]. This also applies with high significance to the comparison of thoracic CT with conventional X-ray of the lungs [167], whereby CT detected either metastasis or a synchronous second carcinoma in approximately 11% of cases and was recommended as a screening method for patients with advanced primary tumours [168]. Due to its high sensitivity and the preferred location of secondary tumours/distant metastases in the lung, chest CT is recommended as an important imaging modality for primary staging in all patients with head and neck tumours [169]. Despite the very low overall incidence of liver metastases, this guideline nevertheless recommends liver imaging as an obligatory part of pre-therapeutic staging (recommendation 7.11: 100% consensus of mandate holders). At this point, it should not go unmentioned that some authors would only recommend abdominal imaging to exclude liver metastases to a limited extent, for example only in N2/3 situations [194] [195].

If a metastasis is detected in a single lymph node of category N2b or N2c, or if an involved lymph node measures more than 3 cm in maximum diameter (N2a or N3), there is a higher risk of distant metastases, a whole-body FDG-PET-CT is recommended as an alternative to CT thorax/abdomen to rule out or objectify distant metastases. for the objectification of distant metastases (sensitivity for the detection of distant metastases 96.8%, specificity 95.4%, positive predictive value 69.8%, and negative predictive value 99.6%) [196]. In a study by the Institute for Quality and Efficiency in Health Care, a benefit assessment of positron emission tomography (PET and PET/CT) for head and neck tumours was carried out. The primary objective was to examine the benefit of the method in metastatic cervical lymphadenopathy for the detection of the unknown primary tumour (cancer of unknown primary tumour, CUP syndrome). In addition, the extent to which PET or PET/CT is superior to standard diagnostic procedures without PET was investigated. A systematic database analysis was carried out for this purpose, whereby only one single usable comparative study could be identified with regard to recurrence-free 2-year survival, which neither proved nor disproved a patient-relevant benefit of PET [190]. For the question of staging of the primary tumour, CT and SPECT showed a higher specificity compared to PET, particularly for the detection of bone invasion [147]. PET also performed no better than CT or MRI for the diagnosis of cervical lymph node metastases, while PET tended to have a higher sensitivity than CT for the detection of distant metastases [157].

For recurrence detection, the few usable studies identified by IQWiG comparing PET vs. a combination of CT and/or MRI showed that PET had a significantly higher pooled sensitivity than the combination of CT and/or MRI. Here, the specificity is reduced by false positive findings due to accumulation in inflammatory lesions. However, FDG-PET showed a higher reliability with a sensitivity of 100% and a specificity of 61-71% than CT and/or MRI [172]. A good pooled sensitivity of 84% for PET/CT was also shown for the detection of an unknown primary tumour, which is why the assumption was made that both the combination with CT and PET alone is able to diagnose additional primary tumours after the primary diagnosis with CT and/or MRI has been completed. This is also confirmed by other studies, according to which FDG-PET not only diagnoses distant metastases more reliably, but also detects 24-26% more primary tumours than CT or MRI alone [172] [197][198].

FDG-PET-CT plays a role in the follow-up of node-positive patients who have undergone primary combined radio-chemotherapy.

In an important, worldwide "practice changing" prospective randomized study, Mehanna et al. [202] found that survival rates were comparable between patients who underwent PET-CT surveillance and those who underwent elective neck dissection. After a median follow-up of 36 months, the 2-year overall survival of the 564 patients included was 84.9% in the image-guided follow-up group (N=54 lymph node dissections) and 81.5% in the lymph node dissection group (N=221). The hazard ratio (for death) clearly supported PET-CT-guided surveillance and indicated non-inferiority to the elective neck dissection group (upper limit of 95% CI for hazard ratio < 1.50; p = 0.004). Since the study was grouped according to the 7th edition of the TNM classification, the recommendation of PET-CT surveillance after primary radiochemotherapy is currently given for all initially node-positive (N+) tumours in view of the possible underestimation in N1-categorized p16-positive oropharyngeal carcinomas in the 8th edition.

Breik et al. [204] favours PET/CT for the follow-up of patients with oral cavity, oropharyngeal and hypopharyngeal carcinomas in the 3-6 month period after the end of therapy. In 140 patients, recurrences or metastases were found in 25%, 60% of them within the first 6 months. Sensitivity/specificity within 3-6 months after the end of therapy was 0.95/0.83 (PET/CT) and 0.60/0.86 (MRI), after 3 months 1.0/0.7 (PET/CT) and 0.50/0.86 (MRI), and after 6 months 0.93/0.87 (PET/CT) and 1.0/0.83 (MRI).

Panendoscopy under anaesthesia includes oesophagoscopy, tracheobronchoscopy, pharyngoscopy (inspection of the nasopharynx, oropharynx and hypopharynx), microlaryngoscopy and inspection of the oral cavity. In analogy to the S3 Guideline on Laryngeal Carcinoma 017-076OL, Chapter 6.4, panendoscopy should be performed as a mandatory part of the primary diagnosis of oropharyngeal and hypopharyngeal carcinomas. It is a central part of primary diagnostics for a more precise diagnosis of the extent of the primary tumour and for the detection of secondary carcinomas.

Background

The frequency of clinically occult secondary carcinomas varies considerably in the literature from 1% to over 10%. There are indications that the frequency of secondary carcinomas depends on the stage of the primary tumour. In patients with oropharyngeal and hypopharyngeal carcinoma who smoke and regularly drink large amounts of alcohol, there is a probability that these noxious substances have also caused carcinomas or precursor lesions in other regions of the upper airways and oropharynx. The extent of this probability is stated very differently in the literature [205] [206] [207] [208] [209][210] [211].

The literature predominantly describes a connection between primary tumours in the head and neck region, particularly the oropharynx and hypopharynx, and the occurrence of syn-/metachronous secondary carcinomas. Stöckli et al. 2001 [211] dealt intensively with this topic and described 16.2% secondary carcinomas in 358 patients examined. Here, 40% of synchronous secondary carcinomas were found in the primary tumour of the oral cavity and pharynx, of which 20% were detected exclusively by panendoscopy (i.e. remained undetected in imaging). Haughey et al 1992[207] found 14% of secondary carcinomas with the highest prevalence in oral cavity, oropharyngeal and hypopharyngeal carcinomas in the largest systematically evaluated series to date, including 40,287 patients. Di Martino et al. 2000 [206] evaluated the tumour registry of the ENT clinic at RWTH Aachen and found 7.7% metachronous carcinomas in 843 patients with head and neck carcinomas, 15.3% of which were in the lungs. With regard to the explicit occurrence of second tumours in the oesophagus in oral cavity carcinoma, figures of 0.8% are given, with significantly higher rates in pharyngeal carcinoma [212]. Koo et al. [213] observed second carcinomas for small oral cavity and pharyngeal carcinoma (tongue T1-2) patients with existing tobacco and alcohol consumption (not quantified) in 14.5-16.3% of patients. In the few never smokers/drinkers, the second carcinoma rate was 0%. Similar observations were published by Rodriguez-Bruno et al. 2011 [209]. Hung et al. [214] in a large cohort of 2,965 patients from the "Taiwanese Longitudinal Health Insurance Database 2000" (high-ranking publication in PloS One) found an odds ratio of 55.3 for synchronous oesophageal cancer in patients with oral cavity/pharyngeal cancer compared to the normal population group (prevalence 2.19% versus 0.04%) and strongly recommended performing panendoscopy in routine primary diagnostics. Sharma et al. 2018 [215] saw 5.56% second cancers (predominantly in the hypopharynx) in 234 patients in Germany, with these most commonly observed in primary oral cavity and oropharyngeal cancers. Less convincingly, Davidson et al. 2000 [205]concluded on the basis of a 154-patient series that routine panendoscopy was unnecessary for 2.6% of secondary cancers.

In England, the "Tumour Assessment and Staging: UK National Multidisciplinary Guidelines" [Mehanna, H et al. 2016] recommends panendoscopy under general anaesthesia as part of the primary diagnosis. It is important that the endoscopy is performed by a "senior surgeon". The authors critically concede that although there is a documented proportion of secondary cancers for panendoscopy in the literature, according to a review by McGarey et al. [McGarey, PO et al. 2016] the proportion of secondary cancers has decreased in the last three decades and therefore rigid oesophagoscopy in particular should only be performed in patients with primary tumours in whom an increased incidence of secondary cancers has been described (oropharynx and hypopharynx are addressed). In the guidelines and the larger studies mentioned here, the anaesthesia- and surgery-associated risk of panendoscopy is considered to be subordinate or negligible in relation to the more precise initial diagnosis and thus undisputed added value for the patient.

The NCCN Guidelines, Version 2.2022, Cancer of the Oro- and Hypopharynx, explicitly recommend performing panendoscopy under general anaesthesia (examination under anaesthesia (EUA) with endoscopy) as part of the pre-therapeutic staging examination

Clinical experience has shown that the imaging of small and early, superficially located squamous cell carcinomas of the mucous membranes of the upper aerodigestive tract is often inadequate, as even the new high-resolution cross-sectional imaging and PET hybrid procedures cannot detect these lesions. For this reason, panendoscopy is considered more important than imaging when it comes to determining the exact extent of the tumour and visualizing metachronous secondary carcinomas (especially in the oesophagus). A distinction must be made between this and the targeted biopsy endoscopy performed for histological verification in the case of apparent abnormalities in the mirror examination or imaging. The latter does not replace the panendoscopy required in the context of staging to rule out secondary carcinomas and visualize the extent of the primary tumour.

The proposal under discussion that panendoscopy should only be performed in cases where there is a history of increased risk [209] is not expedient in the light of the literature. It is known from numerous epidemiological studies that many head and neck tumour patients dissimulate in their medical history as part of the primary diagnosis and to a large extent provide unreliable information on tobacco and alcohol consumption. Even with the use of very extensive epidemiological data collection instruments, it was not possible to overcome the existing inherent retrospective imprecision. In the case of the association with HPV16, this trigger only applies to the oropharynx. Nevertheless, panendocopy should remain an obligatory diagnostic component even for p16-positive oropharyngeal carcinomas, as combined risk factor constellations are predominant, particularly in Germany. Second cancers can occur synchronously or metachronously. Synchronous secondary carcinomas may already be clinically apparent at the time of the manifestation of oropharyngeal and hypopharyngeal carcinoma during the ear, nose and throat examination or one may become aware of them due to the specific symptoms. Panendoscopy is suitable for the exclusion or detection of clinically occult secondary carcinomas and their precursors and cannot be replaced by imaging. According to publications and the prevailing expert opinion, it is therefore one of the mandatory diagnostic measures to be performed prior to a therapeutic decision on histologically proven oropharyngeal or hypopharyngeal carcinoma.

Performance of panendoscopy

Panendoscopy is usually performed together with endoscopy of the expected tumour region, which also includes a tissue sample (biopsy). Palpation of the oral cavity, in particular the tongue, the base of the tongue and the accessible pharyngeal region under anaesthesia during the initial phase of maximum muscle relaxation is considered an important step during panendoscopy. This gives the surgeon a good three-dimensional impression of the extent of the tumour. Panendoscopy addresses the entire upper airway and alimentary canal, i.e. the entire oral cavity, the entire naso-, oro- and hypopharynx and the larynx are inspected. In addition, an endoscopy of the tracheobronchial system and the oesophagus is performed (secondary carcinomas are often found in the distal oesophagus). The oral cavity and oropharynx can be inspected directly without an endoscope, although the mucosa, base of the tongue, hypopharynx and larynx should be assessed with an endoscope. Laryngoscopes, such as the "Kleinsasser tube", are usually used for this purpose. Endoscopy of the tracheobronchial system can be performed using rigid endoscopes with different angles. Oesophagoscopy can also be performed with a rigid, preferably pneumatic oesophagoscope. Due to the possible complications, such as perforation of the oesophageal wall, particularly at the transition from the piriform sinus into the oesophagus, but also distally, some authors recommend performing oesophagoscopy with a flexible endoscope. The disadvantage of a flexible endoscope, particularly in the hypopharynx, is that this region cannot be stretched. Rigid endoscopy is therefore advantageous for inspecting the postcricoid area. Tracheobronchoscopy can also be performed optically with flexibility.

In the presence of hypopharyngeal carcinoma with laryngeal involvement, microlaryngoscopy performed as part of panendoscopy is of particular importance in order to define the extent of the primary tumour. In particular, superficial mucosal changes that cannot be detected by imaging can be easily recognized. The piriform sinus is often compressed in sectional imaging, so that the exact extent of the tumour can often not be precisely determined if there is surrounding oedema. The endoscopic "stretching" of this region is of great additional diagnostic benefit. In addition, microlaryngoscopy performed prior to treatment can determine whether the entire larynx can be adjusted endoscopically in order to possibly perform a transoral laser surgical resection during definitive treatment. In these situations, a mapping biopsy may also be useful.

The findings concerning the primary tumour extension obtained during panendoscopy including palpation are entered or drawn into a prefabricated pictogram. It is advisable to check the resectability and enter this on the document (midline crossing of the base of the tongue, etc.). In the event of resectability, the exact surgical procedure should be determined (transoral adjustability, necessity of reconstruction, type of reconstruction, etc.).

The removal of a tissue sample and its subsequent histopathological examination to detect/exclude of a malignant tumour or a precursor lesion is an essential prerequisite for the initiation of tumour-specific treatment (S1-BDP). In analogy to the S3 Guideline on Laryngeal Carcinoma 017-076OL, Chapter 6.5, a similar procedure should be followed for oropharyngeal and hypopharyngeal carcinoma, although excisional biopsies are much less common here. The biopsy is usually performed as part of panendoscopy. It is generally recommended that imaging relevant to further treatment is carried out before a tissue sample is taken, as the biopsy can lead to tissue reactions that make assessment during imaging more difficult or falsify it.

In the case of macroscopically clearly identifiable advanced tumours, the tissue sample should preferably be taken from the peripheral area of the tumour, i.e. the progression zone, and under no circumstances from the necrotic centre only. However, it is also desirable to collect tumour bases from non-necrotic areas where feasible. The usual form of biopsy for macroscopically clear, advanced tumours is an incisional biopsy with microshears or sharp forceps (Blakesley). An excisional biopsy should only be performed for circumscribed lesions without deep infiltration. This procedure is particularly suitable for older patients in order to avoid a second procedure under anaesthesia in the case of in sano resection (R0). Areas of mucosa that are suspicious for the presence of a precursor lesion should also be biopsied (see above). A so-called brush biopsy is not recommended. Photo documentation of the tumour during panendoscopy under anaesthesia and prior to sampling is recommended and is of great benefit in the subsequent treatment decision. If the histology findings are unexpectedly negative, the biopsy should be repeated at least once. The histomorphological parameters to be indicated are described above; the description of the R status is only useful for the excisional biopsy.

In analogy to the S3 Guideline on Laryngeal Carcinoma 017-076OL, Chapter 6.6. [2], no recommendation can be made for the suitability of SLN biopsy as a method for avoiding elective neck lymph node removal in oropharyngeal and hypopharyngeal carcinoma. Sentinel lymph nodes are those lymph nodes that are closest to the tumour in the lymph drainage area of a malignant tumour. If tumour cells have already been carried into these lymph nodes with the lymph flow and have led to a metastasis, further metastases are likely to be found in downstream lymph nodes. If, on the other hand, no metastases are found in the removed sentinel lymph node, there is a low probability that further lymph node metastases are present. In this respect, this procedure is of particular importance in cN0 neck, as it is hoped that it will eliminate the need for an elective neck dissection. The sentinel lymph node technique is a clinically established technique for breast carcinoma, prostate carcinoma and melanoma.

In the head and neck area, the oral cavity is considered to be an important primary tumour site that can be considered for meaningful SNB. An initial consensus guideline is available [219], which describes the high potential of SNB but does not yet make any recommendations for routine clinical practice. The S3 Guideline on Oral Cavity Carcinoma 007-100OL, Version 3.4, Chapter 8.3, also does not recommend the routine performance of SNB: there is no robust evidence from clinically controlled studies for the suitability of SLN biopsy as a method to avoid elective neck lymph node evacuation. In the most comprehensive and most recent meta-analysis by Liu et al. [220], which is also assessed as having only a low risk of bias, 66 studies with 3566 tongue cancer patients (i.e. also some with oropharyngeal carcinoma) are analysed and the sensitivity of SLN biopsy with regard to the detection of lymph node metastasis is stated as 0.87 [0.85-0.89] (with inclusion of all studies including the validation studies with immediately subsequent neck dissection). Considering only the studies in which patients with negative SLN were followed up and the false negatives were detected over the course, the sensitivity is 0.85 [0.82-0.88]. In the results to date, however, SLN biopsy is equivalent in terms of survival after conventional neck dissections for small squamous cell carcinomas (T1/T2) [221][222]. In terms of postoperative quality of life and functionality, there are advantages for SLN biopsy [223], as well as in terms of lower complication rates [222]. According to the S3 Guideline on Oral Cavity Carcinoma, SLN biopsy can be offered for early, transorally resectable oral cavity carcinomas that do not require a transcervical approach in the same procedure. If the sentinel lymph node is positive and detection is uncertain, a complete neck dissection should be performed.

In more recent studies that primarily focus on the oropharynx and hypopharynx, a meta-analysis by van den Bosch et al. [224] stands out. In a pooled analysis of 19 studies and 377 patients, the sensitivity and negative predictive value were estimated at 0.93 (95% CI: 0.86-0.96) and 0.97 (95% CI: 0.94-0.98). According to the authors, the accuracy of the SNB justifies its place in the diagnosis of patients with oropharyngeal and hypopharyngeal carcinomas. However, randomized studies for further verification are lacking. Further meta-analyses underline the high sensitivity and specificity in oropharyngeal and hypopharyngeal carcinoma [225], but this has not yet led to further recommendations in guidelines. This is probably also due to the fact that many authors do not consider elective selective neck dissection with very low morbidity to be a disadvantage. Werner et al. [226] were also able to show that SNB is safest when several detected lymph nodes (up to three) are removed, so that the assumed advantage over selective neck dissection has diminished.

This chapter will be implemented with minor specifications and updates in analogy to the S3 Guideline on Laryngeal Carcinoma 017-076OL, Chapter 6.7.

In view of a person's right to self-determination, it is solely up to the of-age, consenting patient to decide whether or not a particular medical treatment should be carried out by a doctor. Treatment by the doctor is therefore only justified and thus exempt from punishment if the patient has previously consented to it. Informing the patient about what is to be done to them, by what means and with what risks and consequences is a prerequisite for the patient's informed consent to the treatment [227] [228]. It is a mandatory legal requirement (BGB, MBO, ...) and is the sole responsibility of the doctor. The information must be provided in good time so that the patient can make a well-considered decision about consent (Section 630e (2) no. 2 BGB). In Germany, the Act to Improve Patients' Rights (Patients' Rights Act; [229]) has been in force since 2013. In this law, the standards previously scattered in various legal texts were combined into one law. In particular, the treatment contract is regulated more clearly under the new paragraph §630a BGB. It also stipulates that the patient must be comprehensively informed about all circumstances relevant to the treatment, such as diagnosis, prospects of success, risks and therapy as well as various treatment alternatives. The patient also has a duty to cooperate, particularly with regard to the medical history [228][229]. The law also stipulates the obligation of the treating party to provide information about their own errors, as well as the errors of other treating parties, based on certain circumstances, e.g. a health risk that has arisen. Even if the reversal of the burden of proof to the detriment of the treating party still only comes into effect in connection with gross malpractice, the law regulates numerous simplifications of the burden of proof for the patient. For example, the treating party must prove that they did not make a mistake if, for example, there was a controllable risk, errors were made in the information provided or its documentation or the treating party simply lacked the suitability for the measure carried out, e.g. in the course of a novice operation [227].

A patient who is confronted with the diagnosis of oropharyngeal or hypopharyngeal carcinoma must come to terms with this situation. The informative discussion with the attending physician is of great importance for this. The patient needs sufficient time to come to grips with the diagnosis of "carcinoma". For this reason, information is not usually provided in a single consultation, but as a process that accompanies the course of the disease. In addition to the patient, relatives also play a major role, who should of course only be fully informed about the disease with the patient's consent, as they will support the patient in their home environment. Once the diagnosis has been communicated, the patient is often not fully receptive. Much of what is explained to them in the first phase is often not properly understood, especially the consequences of treatment, be it surgery, radiotherapy or chemotherapy. For this reason, it is also important to inform relatives about the consequences of treatment. Informing patients and relatives together makes communication within the partnership and family easier. This should be communicated to the patient.

As several functions such as voice production, swallowing and breathing can be impaired in the case of oropharyngeal and hypopharyngeal carcinoma, the patient must be given a detailed explanation of the possible disorders that may arise after a specific therapy. This initial informative discussion with the patient and their relatives is important so that they can decide on the right therapy for them. However, the patient will often follow the doctor's recommendation, so it is all the more important to explain the consequences of the treatment. As most patients have no idea of the anatomy of the upper aerodigestive tract, the explanations must be clearly explained to the patient with the aid of diagrams. Many patients also need to be made aware of the seriousness of the disease; this applies in particular to smaller carcinomas, the treatment of which would only lead to minor functional impairment. In order to present the patient with a broad picture of the treatment options following the decision of the interdisciplinary tumour board, it is generally advisable to consult an ENT surgeon as well as a radiotherapist (and an internal oncologist if the treatment option is appropriate), who can accompany the consultation.

The patient must always be informed about the prospects of success. If information is provided on the probability of recovery, this should be given as absolute (and not relative) frequencies where possible [230][231]. The probable risks and consequences of non-therapy should also be explained.

The presence of the patient is also possible (but not obligatory) at tumour board meetings, so that the advantages and disadvantages of various treatment options, including the prospects of success, can be discussed in the patient's presence. A representative of the self-help groups should also be included in the patient's explanation. It is very helpful if contact can be established with a patient who has undergone similar treatment. This gives the patient a clearer picture of the situation after the therapy and gives them a better idea of the functional impairments as well as the rehabilitative options.

If the patient has decided on a therapy or sensible alternative recommended by the interdisciplinary tumour board, this must of course be explained in detail. The information should be provided by the surgeon himself or by a doctor who has sufficient experience in the field of the proposed therapy. It is particularly important for the patient to be informed about the prognosis with regard to voice production, breathing and swallowing as well as visible - and therefore possibly stigmatizing - changes to the face and neck after the therapeutic procedure. It is also important to know whether a permanent tracheostomy or a temporary tracheostomy is being performed and whether a tracheostomy tube needs to be worn. In the case of operations in the oropharyngeal and hypopharyngeal region, aspiration is not an insignificant problem and must be explained to the patient, in addition to the possible impairment of swallowing function and voice production. Appropriately illustrated, standardized information sheets should be used to support the oral information provided to the patient, which is mandatory in all cases. Handwritten entries of important complications in the information sheets are essential for documenting the oral information provided to the patient. According to the Patients' Rights Act, the patient must be given a copy of the information sheet (Act on the Improvement of Patients' Rights). The contents of the information sheet depend on the type of treatment; the radio-oncologist is responsible for providing information about primary radiotherapy, while information on surgical treatment is provided by the ear, nose and throat specialist.

In the case of primary tumour treatment, an appropriate differentiation must be made, including both transoral laser surgery and transcervical surgery. The exact location of the tumour must also be taken into account. In addition to the treatment of the primary tumour, the patient must also be informed about the treatment of the lymphatic drainage channels. The necessity of an elective neck dissection as well as that of a therapeutic neck dissection must be fully explained to the patient. The patient must be informed that changes to the treatment recommendations are possible after the primary tumour has been treated, taking into account the histological findings available at that time. These must then be explained again. Furthermore, in the case of a partial resection of the larynx, the temporary tracheotomy that may be necessary in some cases should be discussed in detail with the patient. As adjuvant therapy in the form of radiochemotherapy is necessary in addition to surgical treatment in many cases of extensive tumours, especially if lymph node metastasis has been detected, the patient must also be informed about this. In particular, it must be explained to the patient why adjuvant therapy in the form of radiotherapy and chemotherapy is necessary despite the surgical extirpation of the tumour. Chemotherapy accompanying radiotherapy has become established in recent years, and patients must be informed in detail about the benefits of this additional treatment and the corresponding side effects.

The informing physician should also consider how the patient can mentally process the information provided. Irrational "subjective theories of illness" should be counteracted.

Despite truthful information, hope can be conveyed even if the prognosis is unfavourable, if necessary by providing information about palliative treatment options.

Staff with experience in psycho-oncology can be helpful for patients with psychological stress and/or their relatives.

In the case of clinical trials, the patient must be informed in detail in advance about the content of the trial and must of course be free to decide whether he or she is available for a corresponding trial. The patient must also be informed in detail if tissue asservation is planned as part of tumour biobanks. The attending physician must explain to the patient the advantages of such a biobank for future research projects and how it can enable later research. Since the majority of oropharyngeal and hypopharyngeal carcinomas are caused by noxious substances such as smoking and alcohol abuse, this connection must be clearly explained to the patient, particularly with regard to their behaviour after treatment. The patient should also be informed about the possibilities of functional rehabilitation, e.g. through speech therapy measures and any PEG placement that may be considered appropriate.

On discharge from hospital, the doctors providing further treatment should be informed of the reasons for the choice of therapy. This concerns not only information about the type and extent of the tumour treated, but also information about decision-making by the tumour board and the patient.