Impact of the Identification of Nonhuman Genetic Signatures in the Diagnosis and Management of Carcinoma of Unknown Primary

J Natl Compr Canc Netw. 2023 Dec 27;22(1D):e237079. doi: 10.6004/jnccn.2023.7079.

Abstract

This report presents the case of a 62-year-old woman who was diagnosed in 1999 with stage I cervical carcinoma treated by surgical resection. In 2021, she presented to the emergency department with a complaint of predominantly right-sided lower back pain. A CT scan of the lumbosacral region revealed a bone lesion in the L5 vertebra and retroperitoneal lymphadenopathies suggestive of malignancy. Histology of the L5 vertebra biopsy showed a poorly differentiated carcinoma with an inconclusive immunophenotypic profile. Treatment for carcinoma of unknown primary was started with a combination of carboplatin and paclitaxel every 21 days. A genomic study of the biopsy specimen performed on the FoundationOne CDx platform identified a nonhuman genetic signature compatible with HPV. The presence of HPV 18 DNA in the specimen was confirmed by PCR-reverse dot blot, and the immunophenotypic profile was expanded, revealing strong and diffuse p16 expression, thus corroborating the molecular findings. In view of these findings, the case was reclassified as a recurrence of the cervical adenocarcinoma that had been diagnosed and treated 23 years earlier. Based on the new results, and according to first-line cervical carcinoma protocols, bevacizumab at 15 mg/kg every 21 days was added to her chemotherapy regimen. The identification of HPV DNA sequences by next-generation sequencing facilitated the correct diagnosis and led to a modification of the first-line therapeutic approach.

Keywords: HPV; algorithm; carnoma; next generation sequencing; unkown origin.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bevacizumab
  • Carcinoma* / drug therapy
  • Female
  • Humans
  • Middle Aged
  • Neoplasms, Unknown Primary* / diagnosis
  • Neoplasms, Unknown Primary* / drug therapy
  • Neoplasms, Unknown Primary* / genetics
  • Paclitaxel / therapeutic use
  • Papillomavirus Infections*
  • Uterine Cervical Neoplasms* / pathology

Substances

  • Bevacizumab
  • Paclitaxel