Detection and Oncologic Outcomes of Head and Neck Squamous Cell Carcinoma of Unknown Primary Origin

Lee, Maxwell; Fowler, Nicole; Adelstein, David J.; Koyfman, Shlomo A.; Prendes, Brandon; Burkey, Brian B.

doi:10.21873/anticanres.14421

Cited by 18 publications

(22 citation statements)

References 26 publications

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“…Primary tumor detection plays a critical role in a treatment regimen and subsequent outcomes, and a full diagnostic workup is outlined in Figure 2 . While TORS has a reported detection rate as high as 94% ( 38 ), unknown primary detection rates are as low as approximately 50% in clinical practice ( 3 , 10 ). TORS is not universally available at all facilities due to need for specialized equipment and training.…”

Section: Discussionmentioning

confidence: 99%

“…SCCUP is defined as metastatic squamous cell carcinoma (SCC) to cervical lymph nodes without evidence of a primary tumor upon physical examination. A primary tumor can evade detection due to a combination of its location, small size, and potential regression of the primary ( 3 ).…”

Section: Introductionmentioning

confidence: 99%

“…Consequently, extensive diagnostic workup is essential to localize the primary site. However, despite exhaustive efforts to find the primary site, overall rates of primary detection are suboptimal, reported as low as approximately 50% ( 3 , 10 ). Since treatment of HNSCC is largely informed by the primary site, SCCUP patients pose a unique challenge.…”

Section: Introductionmentioning

confidence: 99%

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Updates in the management of unknown primary of the head and neck

et al. 2022

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Squamous cell carcinoma (SCC) from an unknown primary tumor (SCCUP) accounts for 2.0%–5.0% of all head and neck cancers. SCCUP presents as enlarged cervical lymph nodes without evidence of a primary tumor upon physical examination. Primary site detection is important to target treatment and avoid treatment-related morbidity. In this review, we discuss updates in SCCUP management. Diagnostic workup should focus on localization of the primary tumor in SCCUP. Initial workup centers on neck biopsy to confirm the presence of SCC. Given the increasing incidence of HPV-related SCC in the oropharynx, HPV testing is crucial. An HPV-positive status can localize the tumor to the oropharynx, a common site for occult tumors. Imaging includes neck CT and/or MRI, and PET/CT. After imaging, panendoscopy, palatine tonsillectomy or diagnostic transoral robotic surgery can facilitate high rates of primary tumor localization. Primary tumor localization influences treatments administered. SCCUP has traditionally been treated aggressively with large treatment fields to all potential disease sites, which can induce weight loss and swallowing dysfunction. As a result, primary localization can reduce radiation fields and provide possible de-escalation to primary surgical management. Advances in intensity-modulated radiation therapy and dose management also have the potential to improve functional outcomes in SCCUP patients. Given the improved prognosis associated with HPV-positive SCCs, HPV tumor status may also inform future treatment de-intensification to reduce treatment-related toxicity.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Updates in the management of unknown primary of the head and neck

et al. 2022

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“…After radiological imaging and clinical examination, the patient is normally scheduled for an examination under general anesthesia (pan-endoscopy). The identification rate is 22–31% after direct pharyngo-laryngoscopy [ 9 , 78 , 79 ], 28–30% after palatine tonsillectomy [ 9 , 80 , 81 ], and 18% after base of the tongue biopsies [ 82 ]. It is noteworthy that the cumulative identification rate differs remarkedly in HPV− and HPV+ patients, with reported cumulative identification rates of 26% versus 65%, respectively [ 9 ].…”

Section: Identification Of the Primary Tumor Site Addressing Hpvmentioning

confidence: 99%

“…Synchronous tumors have been demonstrated to occur in 6–18% of palatine and lingual tonsil cancers [ 9 , 64 , 80 , 81 , 91 , 92 ]. The rate of synchronous cancers in HPV+ cases is reported by two studies, one of which found a rate of 7.7% in HPV+ patients with SCCUP [ 91 ], while a second found a rate of 5% among SCCUP patients where 92% of the synchronous tumors were HPV+, with the highest incidence in the mid-2000s and early 2010s [ 92 ].…”

Section: Identification Of the Primary Tumor Site Addressing Hpvmentioning

confidence: 99%

Human Papillomavirus and Squamous Cell Carcinoma of Unknown Primary in the Head and Neck Region: A Comprehensive Review on Clinical Implications

Larsen

Channir

Buchwald

2021

Viruses

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Squamous cell carcinoma of unknown primary (SCCUP) is a challenging diagnostic subgroup of oropharyngeal squamous cell carcinoma (OPSCC). The incidence of SCCUP is increasing in parallel with the well-documented increase in OPSCC and is likewise driven by the increase in human papillomavirus (HPV). The SCCUP patient often presents with a cystic lymph node metastasis and undergoes an aggressive diagnostic and treatment program. Detection of HPV in cytologic specimens indicates an oropharyngeal primary tumor origin and can guide the further diagnostic strategy. Advances in diagnostic modalities, e.g., transoral robotic surgery and transoral laser microsurgery, have increased the successful identification of the primary tumor site in HPV-induced SCCUP, and this harbors a potential for de-escalation treatment and increased survival. This review provides an overview of HPV-induced SCCUP, diagnostic modalities, and treatment options.

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Early Improved Functional Outcomes in Head and Neck Cancer Patients with Primary Tumor Detection

et al. 2023

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ObjectivesWe characterize functional outcomes in head and neck cancer of unknown primary (CUP) based on primary site identification.MethodsIn this retrospective study, CUP cases were categorized as known primaries (KP) if a tumor was localized after diagnostic workup or persisting unknown primaries (UP). Age, sex, HPV status, diagnostic methods, and treatments regimens were collected. Pretreatment and short‐term posttreatment (3–6 months after completion of treatment) weights, PHQ‐9, Eating Assessment Tool (EAT‐10), and Voice Handicap Index (VHI‐10) scores were compared between UP and KP.ResultsAmong 67 CUP patients, 35 (52.2%) had identified primaries (91.4% oropharyngeal and 8.6% nasopharyngeal). KP patients were younger (58 vs. 64, p = 0.04) and more likely to be HPV‐positive (88.6% vs. 50%, p = 0.002). Overall detection rates were 16.7% for PET/CT, 34.7% for direct laryngoscopy, and 46.6% for transoral robotic oropharyngectomy. Diagnostic workup was not significantly different between groups. Patients with KP received smaller intermediate radiation dose volumes (436.5 vs. 278.9 cc, p = 0.03) and lower doses to the cricopharyngeal muscle (41.6 vs. 24.6 Gy, p = 0.03).Pretreatment weights, PHQ‐9, EAT‐10, and VHI‐10 scores did not differ between groups. However, posttreatment, UP had greater relative weight loss (−14.1% vs. −7.6%, p = 0.032), higher EAT‐10 scores (12.5 vs. 3, p = 0.004), and higher PHQ‐9 scores (6 vs. 1.4, p = 0.017). Specifically, UP reported more stressful swallowing, difficulty swallowing solids and pills, and swallowing affecting public eating.ConclusionKP patients experienced less weight loss, depression, and reduced swallowing dysfunction, highlighting an early functional benefit of primary tumor identification likely driven by reduced radiation treatment volumes.Level of Evidence4 Laryngoscope, 2023

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Detection and Oncologic Outcomes of Head and Neck Squamous Cell Carcinoma of Unknown Primary Origin

Cited by 18 publications

References 26 publications

Updates in the management of unknown primary of the head and neck

Updates in the management of unknown primary of the head and neck

Human Papillomavirus and Squamous Cell Carcinoma of Unknown Primary in the Head and Neck Region: A Comprehensive Review on Clinical Implications

Early Improved Functional Outcomes in Head and Neck Cancer Patients with Primary Tumor Detection

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