Hereditary oral squamous cell carcinoma associated with CDKN2A germline mutation: a case report

J Otolaryngol Head Neck Surg. 2022 Feb 5;51(1):5. doi: 10.1186/s40463-022-00556-y.


Background: Germline CDKN2A mutations are a well-known cause of familial atypical multiple mole melanoma (OMIM #155601) and melanoma-pancreatic cancer syndrome (OMIM #606719). Increased risk of head and neck squamous cell carcinoma (HNSCC), particularly oral squamous cell carcinoma (OSCC) in those with germline CDKN2A mutations, has been described. However, screening for HNSCC is not a routine practice in patients with CDKN2A germline mutations and these mutations are not a conventional test for HNSCC patients without obvious risk factors.

Case presentation: We describe a female with no smoking history who developed oral squamous cell carcinoma at age 39 and had a complex clinical course of recurrent multifocal squamous cell carcinoma (SCC) and carcinoma in situ of the oral cavity and oropharynx. Detailed family history demonstrated that her mother was diagnosed with OSCC and melanoma in her 40 s, and her maternal grandfather was diagnosed with metastatic melanoma in his 40 s. Genetic testing of the patient and her mother revealed CDKN2A c.301G>T mutation. She was referred to genetic counseling as well as to dermatology, gastroenterology, and neurology for cancer surveillance. She was treated with resections and has no evidence of disease 3 years after diagnosis.

Conclusions: We report a family with a CDKN2A c.301 G>T mutation who also have significant history of OSCC, adding to the growing body of literature suggesting increased risk of HNSCC, particularly OSCC, in CDKN2A germline mutation carriers. It is important to consider CDKN2A mutation testing in familial HNSCC and young patients without obvious risk factors. Moreover, surveillance for HNSCC should be routine practice in those with a CDKN2A germline mutation.

Keywords: CDKN2A germline mutation; Case report; Familial atypical multiple moles melanoma; Head and neck squamous cell cancer; Oral squamous cell cancer.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Carcinoma, Squamous Cell* / genetics
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • Female
  • Germ-Line Mutation
  • Head and Neck Neoplasms*
  • Humans
  • Mouth Neoplasms* / diagnosis
  • Mouth Neoplasms* / genetics
  • Mutation
  • Neoplasm Recurrence, Local
  • Skin Neoplasms*
  • Squamous Cell Carcinoma of Head and Neck


  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16