Abstract
High risk HPV types 16 and 18 are associated with cervical cancer and squamous cell carcinoma of the head and neck (SCCHN). Cidofovir is an antiviral drug used to treat HPV-induced laryngeal papillomatosis and other viral infections, with initial reports suggesting activity in cervical carcinoma cells. We investigated the effects of Cidofovir on a naturally HPV-16-transformed SCCHN cell line (UPCI:SCC090), in comparison with a cervical carcinoma cell line (CasKi) of similar viral characteristics, to evaluate its therapeutic potential. HPV-16 gene transcription was only marginally reduced, and the antiviral and p53 restorative effects were modest in SCC90 cells. However, combination with irradiation enhanced the effects of Cidofovir treatment on these cells. Several days of treatment were required for this effect, which may limit its clinical applicability. Future therapies for HPV-associated tumors may include intralesional antiviral therapy in combination with radiation therapy, but optimization for clinical utility is needed.
MeSH terms
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Adult
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Antiviral Agents / pharmacology*
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Blotting, Western
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Carcinoma, Squamous Cell / metabolism
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Carcinoma, Squamous Cell / pathology
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Carcinoma, Squamous Cell / virology*
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Cell Survival / drug effects
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Cell Survival / radiation effects
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Cidofovir
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Cytosine / analogs & derivatives*
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Cytosine / pharmacology*
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Head and Neck Neoplasms / metabolism
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Head and Neck Neoplasms / pathology
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Head and Neck Neoplasms / virology*
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Humans
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Male
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Neoplasm Proteins / metabolism
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Oncogene Proteins, Viral / metabolism
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Organophosphonates / pharmacology*
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Papillomaviridae / classification
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Papillomaviridae / drug effects*
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Papillomavirus Infections / complications
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Papillomavirus Infections / metabolism
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Radiation Tolerance / drug effects
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Repressor Proteins / metabolism
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Reverse Transcriptase Polymerase Chain Reaction / methods
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Tumor Cells, Cultured
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Tumor Suppressor Protein p53 / metabolism
Substances
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Antiviral Agents
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E6 protein, Human papillomavirus type 16
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Neoplasm Proteins
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Oncogene Proteins, Viral
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Organophosphonates
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Repressor Proteins
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Tumor Suppressor Protein p53
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Cytosine
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Cidofovir