title: Squamous cell carcinoma of the oral cavity in nonsmoking women: a new and unusual complication of chemotherapy for recurrent ovarian cancer?
abstract: OBJECTIVE
  To describe occurrences of oral squamous cell carcinoma (SCC) in patients who had received long-term pegylated liposomal doxorubicin (PLD) for ovarian cancer.
  
  
  METHODS
  In our cohort of patients on maintenance PLD for ovarian and related mullerian epithelial malignancies, we encountered two patients with invasive SCC of the oral cavity (one of them multifocal) and one with high-grade squamous dysplasia. Review of patients at our institution receiving PLD for recurrent ovarian cancer identified three additional patients. The duration of treatment, cumulative PLD dose, human papillomavirus (HPV) positivity, BRCA status, stage at diagnosis, outcome, and other characteristics are reviewed.
  
  
  RESULTS
  All five cases were nonsmokers with no known risk factors for HPV and four were negative for p16 expression. Four of the patients had known BRCA mutations whereas one tested negative. Cumulative doses of PLD were >1,600 mg/m2 given over 30-132 months. Three had SCCs staged as T1N0 oral tongue, alveolar ridge (gingival), and multifocal oral mucosa; one had a T2N0 oral tongue; and one had dysplasia. After excision, two were given radiation but recurred shortly thereafter; the others remain well and have had no further exposure to cytotoxic drugs, including PLD.
  
  
  CONCLUSIONS
  Awareness of this possible long-term complication during PLD treatment should enhance the likelihood of early detection of oral lesions in these patients. Decisions to continue maintenance PLD after complete response of the original cancer should perhaps consider the benefits of delaying ovarian cancer recurrence versus the possible risk for a secondary cancer.
authors.affiliation: NYU Cancer Institute, Division of Hematology/Medical Oncology, 462 First Avenue, Building C+D, New York, New York 10022, USA. timomothy.cannon@gmail.com
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Cannon
authors.forename: Dominic W
authors.initials: DW
authors.lastname: Lai
authors.forename: David
authors.initials: D
authors.lastname: Hirsch
authors.forename: Mark
authors.initials: M
authors.lastname: Delacure
authors.forename: Andrea
authors.initials: A
authors.lastname: Downey
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Kerr
authors.forename: Michael
authors.initials: M
authors.lastname: Bannan
authors.forename: Eleni
authors.initials: E
authors.lastname: Andreopoulou
authors.forename: Tamar
authors.initials: T
authors.lastname: Safra
authors.forename: Franco
authors.initials: F
authors.lastname: Muggia
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000175:diagnosis* / Q000473:pathology; D015331:Cohort Studies; D003945:Diagnosis, Oral / Q000379:methods; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000139:chemically induced / Q000175:diagnosis* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects*; D012307:Risk Factors
chemical_list: D000970:Antineoplastic Agents; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin