Correlation among tumor grade, HPV infection and the presence of cancer stem cells in human oral carcinomas

Abstract

Malignant neoplasms are considered the largest global cause of death in humans. Squamous cell carcinoma of the oral cavity (OSCC) is the most common type of cancer in the head and neck region. Oral cancer can be considered a public health problem in Brazil. In 2016, about 15,490 cases of oral cancer were diagnosed in the country. The etiology of cancer is attributed to factors such as tobacco, alcohol and infections, among others. HPV is a DNA virus with specific tropism for squamous epithelium, which has a well-established relationship with oropharyngeal cancer. On the other hand, the role of HPV in the development of OSCCS is still the focus of discussion. HPV16 is thought to be present in 10 to 25% of carcinomas in the oral cavity. All cancers harbor mutations in their genome, some with profound effects on cell biology. In addition to mutations, cancer stem cells (CSCs) represent an essential factor in the maintenance of progenitor cells foci in the tumor environment. In recent decades, CSCs have been linked to resistance to antitumor treatment. In parallel, previous studies have report that HPV-positive oropharyngeal carcinomas respond better to chemotherapy/radiotherapy than HPV-negative carcinomas. This character could be attributed to a lower percentage of CSCs in HPV-positive carcinomas. Despite the studies on this subject, there is still a need to understand the relationship between CSCs, HPV infection and other prognostic factors in oral carcinomas. In order to investigate this aspect, we intend to conduct a retrospective cross-sectional study in human OSCCs, correlating morphological indicators of prognosis with the presence of HPV, determined by real-time PCR, and the expression of CSCs, evidenced by the markers CD44 and CD98.