Although squamous cell carcinoma of the head and neck (SCCHN) is closely linked to tobacco and alcohol use, there is an increasing incidence HPV16-related SCCHN arising in the oropharynx. The mechanisms of viral transmission, carcinogenesis and natural history are not well understood. Here, we report a couple-husband and wife diagnosed synchronously with squamous cell carcinoma of the head and neck wherein the tumors were positive for HPV16 by PCR diagnosis. Both viral genomes were genetically identical and closely related to the revised European prototype, HPV16R. An uncommon signal variant nucleotide was identified in both genomes that is not present in the HPV16R. These tumors likely represent transmission between the couple.