Elucidating the clonal relationship of esophageal second primary tumors in patients with laryngeal squamous cell carcinoma

Abstract

Laryngeal cancer ranks as the second most prevalent upper airway malignancy, following Lung cancer. Although some progress has been made in managing laryngeal cancer, the 5-year survival rate is disappointing. The gradual increase in the incidence of second primary tumors (SPTs) plays a crucial role in determining survival outcomes during long-term follow-up, and the esophagus was the most common site with a worse prognosis. In clinical practice, the treatment of esophageal second primary tumors (ESPT) in patients with laryngeal squamous cell carcinoma (LSCC) has always been challenging. For patients with synchronous tumors, several treatment modalities, such as radiotherapy, chemotherapy and potentially curative surgery are necessary but are typically poorly tolerated. Secondary cancer therapy options for metachronous patients are always constrained by index cancer treatment indications. Therefore, understanding the clonal origin of the second primary tumor may be an important issue in the treatment of patients. LSCC cells demonstrate genetic instability because of two distinct aetiologies (human papillomavirus (HPV)-negative and HPV-positive) disease. Various etiologies exhibit distinct oncogenic mechanisms, which subsequently impact the tissue microenvironment. The condition of the tissue microenvironment plays a crucial role in determining the destiny and clonal makeup of mutant cells during the initial stages of tumorigenesis. This review focuses on the genetic advances of LSCC, the current research status of SPT, and the influence of key carcinogenesis of HPV-positive and HPV-negative LSCC on clonal evolution of ESPT cells. The objective is to gain a comprehensive understanding of the molecular basis underlying the clonal origins of SPT, thereby offering novel perspectives for future investigations in this field.

P53 and pRB induction improves response to radiation therapy in HPV-positive laryngeal squamous cell carcinoma

“…Human Papillomavirus (HPV) infection leads to squamous cancers of the oropharynx, and more studies suggested that HPV infection is also relative to an increased risk of Laryngeal Squamous Cell Carcinoma (LSCC). 25 There is increasing evidence showing that LSCC is associated with HPV infection, but the role of HPV in LSCC has not been conclusively established. 25 , 26 Recent studies have shown that HPV infection is not only tightly associated with laryngeal cancer occurrence and progression but is also related to the sensitivity of oropharyngeal tumors to radiotherapy.…”

“… 25 There is increasing evidence showing that LSCC is associated with HPV infection, but the role of HPV in LSCC has not been conclusively established. 25 , 26 Recent studies have shown that HPV infection is not only tightly associated with laryngeal cancer occurrence and progression but is also related to the sensitivity of oropharyngeal tumors to radiotherapy. 27 Currently, the influence of HPV infection on the radiosensitivity of oropharyngeal tumors is controversial, and most studies have suggested that HPV-positive oropharyngeal tumors can increase radiosensitivity.…”