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Cancer of unknown primary (CUP) in the head and neck region accounts for around 5% of malignancies, predominantly presenting as squamous cell carcinoma (SCCUP). Despite improved diagnostic modalities that have resulted in a decreasing incidence, therapeutic management of SCCUP remains challenging due to conflicting retrospective evidence.
Materials and methods
A comprehensive literature search was performed using the keywords “cancer,” “unknown,” “primary,” “cervical,” “head,” “neck,” “squamous,” “cell,” “carcinoma,” “treatment,” and “diagnosis” across the PubMed database and OpenEvidence platform. Current guidelines, including those from the National Comprehensive Cancer Network (NCCN) and the American Society of Clinical Oncology (ASCO), were analyzed to summarize state-of-the-art diagnostic and therapeutic strategies.
Results
A standardized diagnostic workup is essential and comprises medical history, comprehensive ENT examination, ultrasound-guided core needle biopsy, positron-emission tomography (PET/CT) imaging, and panendoscopy with palatine and lingual tonsillectomy. This approach enables identification of the primary tumor in up to 78% of cases. If a primary tumor is detected, treatment follows site-specific protocols. All SCCUP cases should be reviewed in a multidisciplinary tumor board, taking into account factors such as disease burden, immunohistochemistry (IHC), performance status, comorbidities, potential treatment-related toxicities, patient compliance, and expected functional recovery. Treatment strategies are neck dissection (ND) with adjuvant radiotherapy (RT) or chemoradiotherapy (CRT) if necessary or definitive RT or CRT. Due to inconsistent retrospective studies, it is unclear which treatment modality is currently superior.
Conclusion
Management of SCCUP remains complex and requires individualized multidisciplinary decision-making. Prospective trials are essential to optimize treatment strategies.
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ASCO
American Society of Clinical Oncology
CI
Confidence interval
CPS
Combined positive score
CRT
Chemoradiotherapy
CT
Computed tomography
CUP
Cancer unknown primary
DFS
Disease-free survival
EBV
Epstein-Barr virus
ENE
Extranodal extension
ENT
Ear nose throat
FDG
18F-fluorodesoxyglucose
5‑FU
5‑fluorouracil
HNSCC
Head and neck squamous cell carcinoma
HPV
Human papillomavirus
IHC
Immunohistochemistry
IMRT
Intensity-modulated radiotherapy
L1
Lymphovascular invasion
MMC
Mitomycin C
MRI
Magnet resonance imaging
NBI
Narrow-band imaging
NCCN
National Comprehensive Cancer Network
ND
Neck dissection
OS
Overall survival
PAX8
Paired box gene‑8 protein
PCR
Polymerase chain reaction
PD-L1
Programmed cell death 1 ligand
PET
Positron-emission tomography
Pn1
Perineural invasion
RR
Relative risk
RT
Radiotherapy
S100
S100 protein
SCCUP
Squamous cell carcinoma of unknown primary
SOX10
Transcription factor SOX10
TLM
Transoral laser microsurgery
TORS
Transoral robotic surgery
TTF‑1
Thyroidal transcription factor 1
UV
Ultraviolet
Introduction
Cancer of unknown primary (CUP) encompasses a heterogeneous group of histologically confirmed metastatic cancers where the primary site remains unknown despite standardized diagnostic workup [1]. In the head and neck region, cervical CUP accounts for fewer than 5% of all malignancies, with approximately 90% of these cases being squamous cell carcinoma of unknown primary (SCCUP) [2, 3].
Detecting the primary tumor is often challenging due to its small size and anatomic location [4]. A quick diagnostic workup is essential, as treatment delays increase the risk of tumor progression and worsen patient outcome [5].
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Advancements in diagnostic methods have improved primary tumor detection, leading to a decreased incidence of SCCUP [6]. Today, only around 3% of patients presenting with suspicious cervical lymph nodes retain the diagnosis of SCCUP after thorough evaluation [2].
Nevertheless, therapeutic management of SCCUP remains difficult. Current treatment guidelines rely primarily on retrospective studies with varied therapeutic approaches, as prospective randomized trials are rare. Furthermore, the rising incidence of human papillomavirus (HPV)-driven SCCUP limits the applicability of historical data to modern patient populations. This review provides an overview of current diagnostic strategies and treatment approaches for patients with SCCUP.
Materials and methods
A comprehensive literature search was performed using the keywords “cancer,” “unknown,” “primary,” “cervical,” “head,” “neck,” “squamous,” “cell,” “carcinoma,” “treatment,” and “diagnosis” across the PubMed database and OpenEvidence platform. In addition, current clinical practice guidelines were reviewed, including those from the National Comprehensive Cancer Network (NCCN; version 5.2025, August 12, 2025) and the American Society of Clinical Oncology (ASCO) [7, 8].
Results and discussion
Diagnostic workup
Central to the management of SCCUP is a standardized, guideline-based diagnostic workup to identify the occult primary tumor to enable site-directed therapy. A systematic flowchart outlining the diagnostic recommendations is presented in Fig. 1.
Fig. 1
Diagnostic procedure in squamous cell carcinoma of unknown primary (SCCUP)
A detailed medical history is essential before further diagnostic interventions are performed. Important factors include the patient’s age, exposure to carcinogens, and the dynamics of cervical lymphadenopathy. Symptoms such as dysphagia, hoarseness, nasal obstruction, epistaxis, otalgia, or hearing loss may provide valuable clues about the location of the primary [8]. Additionally, risk factors for cutaneous SCC including excessive UV light exposure, previous cutaneous head and neck cancers, immunosuppression, or epidemiological factors suggestive of nasopharyngeal cancer should be carefully evaluated [8, 9].
A thorough ENT examination should encompass:
Inspection of the oral cavity, oropharynx, nasopharynx, larynx, and hypopharynx, with particular attention on the palatine tonsils, base of tongue, and nasopharynx, as over 90% of occult primaries originate in these regions [4].
Palpation of the floor of the mouth, palatine tonsils, and base of tongue.
Flexible endoscopy enhanced by narrow-band imaging (NBI), which can improve visualization and detect approximately 35% of occult primary tumors [10].
Use of the Valsalva maneuver during laryngoscopy to better inspect the piriform sinuses.
Dermatological evaluation when cutaneous SCCUP is suspected [8].
Cervical ultrasonography to assess nodal involvement and to identify potential primary tumors in the salivary glands [8].
Histopathology and imaging
If no primary tumor is detected in the clinical examination, ultrasound-guided core needle biopsy of the lymph node is recommended. This technique achieves a diagnostic accuracy exceeding 90%, surpassing fine-needle aspiration while carrying only a slightly higher risk of complications [11]. Core needle biopsies also enable immunohistochemical (IHC) analyses, which can refine diagnostic pathways and avoid the general anesthesia required for surgical excision of cervical lymph nodes [7, 8, 12].
Key IHC markers for SCCUP include p16, HPV-PCR, EBV, and PD-L1. HPV-driven SCCUP accounts for 38.9–80% of cases [13, 14] and is associated with a favorable prognosis [15]. A p16-positive/HPV-positive status strongly suggests an oropharyngeal origin [16], whereas EBV positivity points to nasopharyngeal cancer [17]. It is noteworthy that p16-positive/HPV-negative SCC can also arise in the lungs and skin. PD-L1 is important in cases of local recurrence or distant metastasis [18].
While reliable IHC markers for cutaneous SCC are lacking, UV-signature analysis via next-generation sequencing may aid in identifying cutaneous origins in HPV-/EBV-negative SCCUP, although this method is not yet routinely applied [19]. For other tumor entities, additional markers may guide diagnosis towards thyroid primaries (e.g., thyroglobulin, calcitonin, PAX8, TTF-1), pulmonary tumors (TTF-1), salivary gland neoplasms, or melanoma (S100, SOX10).
If core needle biopsy is not feasible or yields nondiagnostic results, surgical excision of the lymph node should be performed. Cross-sectional imaging with contrast-enhanced computer tomography (CT) combined with 18F-fluorodesoxyglucose (FDG) positron-emission tomography (PET) is recommended, as it significantly outperforms CT or magnet resonance imaging (MRI) alone [20]. PET findings also facilitate targeted biopsies during panendoscopy.
Endoscopic evaluation and surgical diagnostics
When initial diagnostic efforts to identify the primary tumor fail, panendoscopy is indicated. Routine random biopsies should be avoided because of their limited effectiveness in detecting the primary tumor [8]. If the primary tumor remains unknown, the following steps should be performed during initial panendoscopy:
Unilateral SCCUP: Ipsilateral palatine tonsillectomy with frozen section analysis is recommended. If the frozen sections show no tumor, an ipsilateral lingual tonsillectomy via transoral laser microsurgery (TLM) or transoral robotic surgery (TORS) should be performed. Contralateral tonsillectomy is reserved for cases with suspicious clinical findings.
Bilateral SCCUP: Lingual tonsillectomy with frozen section on the side with the greater tumor burden is recommended. If negative, contralateral lingual tonsillectomy and, if necessary, ipsilateral palatine tonsillectomy should follow. Bilateral palatine tonsillectomy after bilateral lingual tonsillectomy is discouraged, as it does not improve detection rates and carries an increased risk of bleeding [8]. All specimens should be side-marked to facilitate potential extension to complete (R0) resection upon identification of the primary tumor [8].
Although prospective data are limited, retrospective studies support this stepwise approach: panendoscopy alone detects primary tumors in approximately 20–30% of cases [8]; the addition of ipsilateral tonsillectomy raises detection rates to 30–50% [8]; lingual tonsillectomy further increases detection rates to 50–60% [21]; and combined diagnostic protocols—including PET-CT, panendoscopy, and palatine and lingual tonsillectomy—have achieved detection rates of up to 78% [8]. In bilateral SCCUP, priority should be given to examining the base of the tongue, as contralateral metastases occur in 26.7% of T1/T2 base of tongue cancers compared to 8–10% in T1/T2 tonsil cancers [22, 23].
Treatment
If a primary tumor is identified, treatment should follow site-specific guidelines [7]. Otherwise, therapeutic decisions can be challenging due to the absence of prospective trials and inconsistent results comparing neck dissection (ND) + adjuvant radiotherapy (RT) or chemoradiotherapy (CRT) with definitive RT/CRT. The exact radiation fields and doses can be found in the ASCO and NCCN guidelines and are not listed in this paper for a better overview [7, 8].
Some smaller studies have suggested improved overall survival (OS) and better local control with ND followed by adjuvant therapy [24, 25]. However, these studies were limited by small sample sizes, differences in nodal status, and heterogeneous treatment protocols. Larger trials and meta-analyses encompassing over 1700 patients have found no significant difference in OS between ND combined with RT/CRT and RT/CRT alone [26, 27]. Furthermore, intensity-modulated radiotherapy (IMRT) achieves local control rates of around 90% while minimizing toxicity [29].
Given these uncertainties, all cases should be reviewed in a multidisciplinary tumor board, taking into account factors such as disease burden, IHC findings, performance status, comorbidities, potential treatment-related toxicities, patient compliance, and expected functional recovery [7, 8]. Triple-modality treatment (ND plus CRT) should generally be avoided, and patients presenting with clinical evidence of extranodal extension (ENE) or a high tumor burden are not recommended for upfront surgery to prevent cumulative toxicities [8]. A systematic therapeutic flowchart is provided in Fig. 2.
Fig. 2
Treatment of squamous cell carcinoma of unknown primary (SCCUP)
Three distinct subgroups warrant tailored management approaches:
Cutaneous SCCUP
Ipsilateral ND (± parotidectomy) combined with adjuvant or definitive RT is recommended, while mucosal irradiation should be avoided.
EBV+SCCUP
For occult nasopharyngeal primaries, CRT with bilateral irradiation of the nasopharynx, retropharyngeal nodes, and neck is advised, sparing the oropharyngeal mucosa.
EBV – SCCUP
Treatment strategies depend on tumor burden and individual patient factors.
Unilateral disease, single node <3 cm, no ENE
Management options for unilateral disease with a single lymph node less than 3 cm and no ENE include ipsilateral ND including at least level II-IV, with or without adjuvant RT or definitive RT alone.
Adjuvant RT is recommended in the presence of multiple positive nodes, lymphovascular invasion (L1), vascular invasion (V1), perineural invasion (Pn1), or involvement of deeper nodal levels, and should commence within 6 weeks postoperatively [7, 8].
In carefully selected patients presenting with solitary small nodes, excellent compliance, and high-quality ND (yielding more than 18 nodes) performed with panendoscopy including palatine and lingual tonsillectomy, omitting adjuvant RT can be considered [8]. This approach is supported by improved imaging accuracy, comprehensive pretherapeutic evaluation of occult primaries, and reliable endoscopic monitoring of the tonsillar fossae and base of tongue during follow-up, as outlined in the ASCO guidelines [8].
In contrast, a meta-analysis of 965 SCCUP patients—608 treated with both neck and mucosal irradiation and 357 with neck-only irradiation—revealed that adding mucosal irradiation significantly reduced the incidence of primary tumor development during follow-up (12 vs. 16%; relative risk [RR] 0.59, 95% confidence interval [CI] 0.39–0.89; p = 0.01) [29]. Moreover, mucosal irradiation was associated with improved OS (RR 0.75, 95% CI 0.61–0.92; p = 0.06), disease-free survival (DFS; RR 0.75, 95% CI 0.61–0.92; p = 0.005), and reduced neck recurrence rates (RR 0.72, 95% CI 0.56–0.92; p = 0.009) [29]. It is important to acknowledge that outcomes derived from cohorts receiving radiation therapy may not be directly applicable to patients managed exclusively with surgical intervention given the absence of a potential abscopal effect on occult primary tumors in surgery-alone approaches.
In our view, indications for adjuvant RT and mucosal irradiation in the context of definitive RT should be applied generously, with a thorough risk–benefit assessment and shared decision-making involving the patient. In cases with ENE, adjuvant CRT is necessary [7, 8].
Unilateral, single node > 3 cm or multiple nodes, no ENE, M0
The preferred treatment approach involves definitive CRT or ipsilateral ND with adjuvant RT [7, 8].
Unilateral with ENE, M0
In cases with extranodal extension (ENE), definitive CRT is advised.
Bilateral SCCUP, M0
For bilateral nodal involvement, definitive CRT is the treatment of choice [7, 8]. The ASCO guidelines suggest bilateral ND followed by RT in carefully selected patients with low-volume disease, although the precise definitions of low- versus high-volume disease remain unclear [8]. In suspected ENE, definitive CRT is preferred.
Systemic therapy and M1
Data specific to SCCUP in the metastatic setting are limited; thus, recommendations are mainly based on evidence from head and neck squamous cell carcinoma (HNSCC) with known primaries. Cisplatin remains the standard agent for both definitive and adjuvant CRT [7, 8]. For patients ineligible for cisplatin, alternative regimens such as docetaxel or 5‑fluorouacil (5-FU)/mitomycin C (MMC) may be employed [7]. In metastatic disease, pembrolizumab combined with platinum and 5‑FU is indicated for patients with a combined positive score (CPS) < 1, whereas pembrolizumab monotherapy is recommended for those with CPS ≥ 1 [7].
Conclusion and outlook
Therapeutic management of SCCUP remains challenging due to conflicting evidence from retrospective studies. Treatment should be individualized and discussed in a multidisciplinary tumor board. Prospective data are needed, and future directions may include treatment de-escalation in selected patients, as suggested by studies on p16+ oropharyngeal cancer demonstrating dose reduction in RT without compromising survival rates [30]. Moreover, the potential role of neoadjuvant PD-L1 antibodies, analogous to the KEYNOTE-689 trial, warrants investigation in SCCUP.
Take-home message
Standardized diagnostic workup is essential and comprises medical history, comprehensive ENT examination, ultrasound-guided core needle biopsy, PET/CT imaging, and panendoscopy with palatine and lingual tonsillectomy. This approach enables identification of the primary tumor in up to 78% of cases. All SCCUP cases should be reviewed in a multidisciplinary tumor board, taking into account factors such as disease burden, IHC, performance status, comorbidities, potential treatment-related toxicities, patient compliance, and expected functional recovery. Treatment strategies are ND with adjuvant RT/CRT if necessary or definitive RT/CRT.
Acknowledgements
The authors would like to thank Dr. Madita Buch and Dr. Finn Mildner for their assistance in proofreading and for valuable support in improving the language of the manuscript.
Conflict of interest
M. Kloppenburg, M. Santer, L. Schmutzler, F. Johnson, B. Hofauer, and T. Steinbichler declare that they have no competing interests.
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Krämer A, Bochtler T, Pauli C, Baciarello G, Delorme S, Hemminki K, et al. Cancer of unknown primary: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2023;34(3):228–46. https://doi.org/10.1016/j.annonc.2022.11.013.CrossRefPubMed
2.
Waltonen JD, Ozer E, Hall NC, Schuller DE, Agrawal A. Metastatic carcinoma of the neck of unknown primary origin: evolution and efficacy of the modern workup. Arch Otolaryngol Head Neck Surg. 2009;135(10):1024–9. https://doi.org/10.1001/archoto.2009.145.CrossRefPubMed
3.
Gule-Monroe MK, Calle S, Policeni B, Juliano AF, Agarwal M, Chow LQM, et al. Expert panel on neurological imaging. ACR appropriateness criteria® staging and post-therapy assessment of head and neck cancer. J Am Coll Radiol. 2023;20(11S):S521–64. https://doi.org/10.1016/j.jacr.2023.08.008. PMID: 38040469.CrossRefPubMed
4.
Cianchetti M, Mancuso AA, Amdur RJ, Werning JW, Kirwan J, Morris CG, et al. Diagnostic evaluation of squamous cell carcinoma metastatic to cervical lymph nodes from an unknown head and neck primary site. Laryngoscope. 2009;119(12):2348–54. https://doi.org/10.1002/lary.20638.CrossRefPubMed
5.
Pynnonen MA, Gillespie MB, Roman B, Rosenfeld RM, Tunkel DE, Bontempo L, et al. Clinical practice guideline: evaluation of the neck mass in adults. Otolaryngol Head Neck Surg. 2017;157(2 Suppl):S1–S30. https://doi.org/10.1177/0194599817722550.CrossRefPubMed
6.
Binder C, Matthes KL, Korol D, Rohrmann S, Moch H. Cancer of unknown primary: epidemiological trends and relevance of comprehensive genomic profiling. Cancer Med. 2018;7(9):4814–24. https://doi.org/10.1002/cam4.1689. PMID: 30019510.CrossRefPubMedPubMedCentral
7.
National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Head and Neck Cancers. Version 2.2025. Plymouth Meeting (PA): National Comprehensive Cancer Network. 2025. https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1437. Accessed 22 Aug 2025.
8.
Maghami E, Ismaila N, Alvarez A, Chernock R, Duvvuri U, Geiger J, et al. Diagnosis and management of squamous cell carcinoma of unknown primary in the head and neck: ASCO Guideline. J Clin Oncol. 2020;38(22):2570–96. https://doi.org/10.1200/JCO.20.00275.CrossRefPubMed
Di Maio P, Iocca O, De Virgilio A, Giudice M, Pellini R, D’Ascanio L, et al. Narrow band imaging in head and neck unknown primary carcinoma: A systematic review and meta-analysis. Laryngoscope. 2020;130(7):1692–700. https://doi.org/10.1002/lary.28350.CrossRefPubMed
11.
Han F, Xu M, Xie T, Wang JW, Lin QG, Guo ZX, et al. Efficacy of ultrasound-guided core needle biopsy in cervical lymphadenopathy: A retrospective study of 6,695 cases. Eur Radiol. 2018;28(5):1809–17. https://doi.org/10.1007/s00330-017-5116-1.CrossRefPubMed
12.
Park GC, Roh JL, Cho KJ, Kim JS, Jin MH, Choi SH, et al. 18F-FDG PET/CT vs. human papillomavirus, p16 and Epstein-Barr virus detection in cervical metastatic lymph nodes for identifying primary tumors. Int J Cancer. 2017;140(6):1405–12. https://doi.org/10.1002/ijc.30550. PMID: 27943271.CrossRef
13.
Lee M, Jo U, Song JS, Lee YS, Woo CG, Kim DH, et al. Clinicopathologic characterization of cervical metastasis from an unknown primary tumor: a multicenter study in Korea. J Pathol Transl Med. 2023;57(3):166–77. https://doi.org/10.4132/jptm.2023.04.12. PMID: 37194150.CrossRefPubMedPubMedCentral
14.
Boscolo-Rizzo P, Schroeder L, Romeo S, Pawlita M. The prevalence of human papillomavirus in squamous cell carcinoma of unknown primary site metastatic to neck lymph nodes: a systematic review. Clin Exp Metastasis. 2015;32(8):835–45. https://doi.org/10.1007/s10585-015-9744-z.CrossRefPubMed
15.
Tribius S, Hoffmann AS, Bastrop S, Görögh T, Haag J, Röcken C, et al. HPV status in patients with head and neck carcinoma of unknown primary site: HPV, tobacco smoking, and outcome. Oral Oncol. 2012;48(11):1178–84. https://doi.org/10.1016/j.oraloncology.2012.05.022. PMID: 22739067.CrossRefPubMed
16.
Davis KS, Byrd JK, Mehta V, Chiosea SI, Kim S, Ferris RL, et al. Occult primary head and neck squamous cell carcinoma: utility of discovering primary lesions. Otolaryngol Head Neck Surg. 2014;151(2):272–8. https://doi.org/10.1177/0194599814533494.CrossRefPubMedPubMedCentral
17.
Luo WJ, Feng YF, Guo R, et al. Patterns of EBV-positive cervical lymph node involvement in head and neck cancer and implications for the management of nasopharyngeal carcinoma T0 classification. Oral Oncol. 2019;91:7–12. https://doi.org/10.1016/j.oraloncology.2019.02.020. PMID: 30878121.CrossRefPubMed
18.
Krämer A, Bochtler T, Pauli C, Baciarello G, Delorme S, Hemminki K, et al. Cancer of unknown primary: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2023;34(3):228–46. https://doi.org/10.1016/j.annonc.2022.11.013.CrossRefPubMed
19.
Mueller SA, Gauthier MA, Ashford B, Gupta R, Gayevskiy V, Ch’ng S, et al. Mutational patterns in metastatic cutaneous squamous cell carcinoma. J Invest Dermatol. 2019;139(7):1449–1458.e1. https://doi.org/10.1016/j.jid.2019.01.008.CrossRefPubMed
20.
Rudmik L, Lau HY, Matthews TW, Bosch JD, Kloiber R, Molnar CP, et al. Clinical utility of PET/CT in the evaluation of head and neck squamous cell carcinoma with an unknown primary: a prospective clinical trial. Head Neck. 2011;33(7):935–40. https://doi.org/10.1002/hed.21566.CrossRefPubMed
21.
Patel SA, Magnuson JS, Holsinger FC, Karni RJ, Richmon JD, Gross ND, et al. Robotic surgery for primary head and neck squamous cell carcinoma of unknown site. JAMA Otolaryngol Head Neck Surg. 2013;139(11):1203–11. https://doi.org/10.1001/jamaoto.2013.5189.CrossRefPubMed
22.
Punjabi N, Sharma A, Park J, Kennedy K, Inman JC. A systematic review of occult contralateral neck metastasis in tonsillar squamous cell carcinoma. Laryngoscope. 2025;135(1):27–33. https://doi.org/10.1002/lary.31677.CrossRefPubMed
23.
Last AS, Pipkorn P, Chen S, Kallogjeri D, Zenga J, Rich JT, et al. Risk and rate of occult contralateral nodal disease in surgically treated patients with human papillomavirus-related squamous cell carcinoma of the base of the tongue. JAMA Otolaryngol Head Neck Surg. 2020;146(1):50–6. https://doi.org/10.1001/jamaoto.2019.3277. PMID: 31697348.CrossRefPubMed
24.
Amsbaugh MJ, Yusuf M, Gaskins J, Silverman C, Potts K, Bumpous J, et al. Neck dissection for unknown cancer of the head and neck in the era of chemoradiation. Am J Otolaryngol. 2017;38(5):588–92. https://doi.org/10.1016/j.amjoto.2017.06.006.CrossRefPubMed
25.
Lou J, Wang S, Wang K, Chen C, Zhao J, Guo L. Squamous cell carcinoma of cervical lymph nodes from an unknown primary site: The impact of neck dissection. J Cancer Res Ther. 2015;11(Suppl 2):C161–C7. https://doi.org/10.4103/0973-1482.168178.CrossRefPubMed
26.
Balaker AE, Abemayor E, Elashoff D, John StMA. Cancer of unknown primary: does treatment modality make a difference? Laryngoscope. 2012;122(6):1279–82. https://doi.org/10.1002/lary.22424.CrossRefPubMed
27.
Demiroz C, Vainshtein JM, Koukourakis GV, Gutfeld O, Prince ME, Bradford CR, et al. Head and neck squamous cell carcinoma of unknown primary: neck dissection and radiotherapy or definitive radiotherapy. Head Neck. 2014;36(11):1589–95. https://doi.org/10.1002/hed.23479.CrossRefPubMed
28.
Kamal M, Mohamed ASR, Fuller CD, Sturgis EM, Johnson FM, Morrison WH, et al. Outcomes of patients diagnosed with carcinoma metastatic to the neck from an unknown primary source and treated with intensity-modulated radiation therapy. Cancer. 2018;124(7):1415–27. https://doi.org/10.1002/cncr.31235.CrossRefPubMed
Adelstein DJ, Ismaila N, Ku JA, Burtness B, Swiecicki PL, Mell L, et al. Role of treatment deintensification in the management of p16+ oropharyngeal cancer: ASCO Provisional Clinical Opinion. J Clin Oncol. 2019;37(18):1578–89. https://doi.org/10.1200/JCO.19.00441.CrossRefPubMed
