Squamous Cell Carcinoma of the Oral Cavity in Nonsmoking Women: A New and Unusual Complication of Chemotherapy for Recurrent Ovarian Cancer? PLD (pegylated liposomal doxorubicin)

Squamous Cell Carcinoma of the Oral Cavity in Non smokingWomen: A New and Unusual Complication of Chemotherapy for Recurrent Ovarian Cancer?

Abstract
Purpose.
To describe occurrences of oral squamous cell carcinoma (SCC) in patients who had received long-term pegylated liposomal doxorubicin (PLD) for ovarian cancer.

Patients and 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/m(2) 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.

Conclusion. 
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. 

The finding of oral SCC in patients on long-term PLD
maintenance should alert oncologists to have a high index of
suspicion with any oral complaints that arise, and suggests a
possible need for regular oral examinations in this treatment
population. How long to continue maintenance with PLD after
a CR has been achieved is an unanswered question. The possible
risks to patients receiving maintenance PLD beyond CR
must be weighed against the presumed benefits of delaying
ovarian cancer recurrence on an individual basis.