J Pathol Transl Med.  2023 May;57(3):166-177. 10.4132/jptm.2023.04.12.

Clinicopathologic characterization of cervical metastasis from an unknown primary tumor: a multicenter study in Korea

• Lee M
• Jo U
• Song JS
• Lee YS
• Woo CG
• Kim DH
• Kim JY
• Yoon SO
• Cho KJ

• KMID: 2542283
• DOI: http://doi.org/10.4132/jptm.2023.04.12

Abstract

Background
Research regarding cervical metastasis from an unknown primary tumor (CUP) according to human papillomavirus (HPV) and Epstein-Barr virus (EBV) status in Korea has been sporadic and small-scale. This study aims to analyze and understand the characteristics of CUP in Korea according to viral and p16 and p53 status through a multicenter study.
Methods
Ninety-five cases of CUP retrieved from six hospitals in Korea between January 2006 and December 2016 were subjected to high-risk HPV detection (DNA in situ hybridization [ISH] or real-time polymerase chain reaction), EBV detection (ISH), and immunohistochemistry for p16 and p53.
Results
CUP was HPV-related in 37 cases (38.9%), EBV-related in five cases (5.3%), and unrelated to HPV or EBV in 46 cases (48.4%). HPV-related CUP cases had the best overall survival (OS) (p = .004). According to the multivariate analysis, virus-unrelated disease (p = .023) and longer smoking duration (p < .005) were prognostic factors for poor OS. Cystic change (p = .016) and basaloid pattern (p < .001) were more frequent in HPV-related cases, and lymphoepithelial lesion was frequent in EBV-related cases (p = .010). There was no significant association between viral status and p53 positivity (p = .341), smoking status (p = .728), or smoking duration (p = .187). Korean data differ from Western data in the absence of an association among HPV, p53 positivity, and smoking history.
Conclusions
Virus-unrelated CUP in Korea had the highest frequency among all CUP cases. HPV-related CUP is similar to HPV-mediated oropharyngeal cancer and EBVrelated CUP is similar to nasopharyngeal cancer in terms of characteristics, respectively.

Keyword

Unknown primary neoplasms; Lymph node metastasis; Human papillomavirus virus; Epstein-Barr virus infections

Figure

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  Fig. 1. Cervical lymph node metastasis from an unknown primary tumor (CUP). Human papillomavirus (HPV)–related CUP shows a basaloid pattern (A) and is positive for p16 immunohistochemistry (B). Epstein-Barr virus (EBV)–related CUP (C) was confirmed by EBV in situ hybridization (ISH) (D). HPV- and EBV-unrelated CUP (E, F) was defined as cases that are negative for p16, HPV ISH, HPV real-time polymerase chain reaction, and EBV ISH results. (G) Cystic change in the HPV-related CUP. (H) Keratinization in the HPV- and EBV-unrelated CUP.

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  Fig. 2. Comparison of overall survival in cervical metastasis from an unknown primary tumor according to smoking status (A,B), smoking duration (C, D), and p16 (E) and p53 (F).

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  Fig. 3. Comparison of overall survival according to viral status in cervical metastasis from an unknown primary tumor and cervical metastasis with proven primary sites. (A) The human papillomavirus (HPV)–related cervical metastasis from an unknown primary tumor (CUP) cases had the longest overall survival, and the HPV- and Epstein-Barr virus (EBV)–unrelated CUP patients had the worst prognosis, with a significant difference among the three groups. (B) In cervical metastasis with proven primary sites, there was no difference in overall survival according to viral status.

Reference

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