The role of Epstein–Barr virus in diagnosis of primary lesion in patients with squamous cell carcinoma metastases of unknown primary origin

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Abstract

Introduction. Human papilloma virus (HPV) – associated oropharyngeal squamous cell carcinoma is identified as a separate nosological entity of head and neck squamous cell carcinoma. This pathology is often associated with metastases with unknown primary origin. If they are located in the cervical lymph nodes, the primary lesion can be located in the nasopharynx. Considering that keratinizing and nonkeratinizing nasopharyngeal cancer is often accompanied by coexistence of HPV and Epstein–Barr virus (EBV), a theory was proposed that EBV can promote HPV infection.

Aim. To determine the role of EBV in determination of the primary lesion in patients with squamous cell metastases of unknown origin.

Materials and methods. For determination of the supposed link between metastases in the cervical lymph nodes from unknown primary origin and EBV DNA, we examined 151 patients with metastases of squamous cell carcinoma in the cervical lymph nodes from unknown primary origin. Surrogate EBV DNA marker was found in 33 patients.

Results. An association between EBV DNA in serum and nasopharyngeal squamous cell carcinoma was found. Rare incidence of metastases from unknown primary origin is supposedly results from small size of the primary lesion and submucosal tumor location in combination with early lymphatic metastasis.

Conclusion. To not miss clinically hidden nasopharyngeal cancer, interdisciplinary interaction and quantitative measurement of serum EBV DNA are necessary.

About the authors

K. A. Zolotarev

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia; N.V. Sklifosovsky Institute of Clinical Medicine , Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University); Oncological Center No. 1 – a branch of the S. S. Yudin City Clinical Hospital, Moscow Healthcare Department

Author for correspondence.
Email: zolotarev31@mail.ru
ORCID iD: 0000-0002-9015-7030
Russian Federation, 24 Kashirskoe Shosse, Moscow 115522; Bld. 2, 11 Rossolimo St., Moscow 119021; 18A Zagorodnoye Shosse, Moscow 117152

A M. Mudunov

Clinical Hospital “Lapino” of the “Mother and Child” Group of companies

Email: zolotarev31@mail.ru
ORCID iD: 0000-0002-0918-3857
Russian Federation, 111 1st Uspenskoe Shosse, Lapino, Moscow Region 143081

Yu. V. Alymov

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

Email: zolotarev31@mail.ru
ORCID iD: 0000-0002-2283-1812
Russian Federation, 24 Kashirskoe Shosse, Moscow 115522

O. A. Saprina

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

Email: zolotarev31@mail.ru
ORCID iD: 0000-0002-6851-9867
Russian Federation, 24 Kashirskoe Shosse, Moscow 115522

N. N. Tatintsyan

RUDN Universtiy

Email: zolotarev31@mail.ru
ORCID iD: 0009-0007-7905-2522
Russian Federation, 6 Miklukho-Maklaya St., Moscow 117198

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Copyright (c) 2026 Zolotarev K.A., Mudunov A.M., Alymov Y.V., Saprina O.A., Tatintsyan N.N.

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