Phytochemicals as Potential Chemopreventive and Chemotherapeutic Agents for Emerging Human Papillomavirus–Driven Head and Neck Cancer: Current Evidence and Future Prospects

Abstract

Head and neck cancer (HNC) usually arises from squamous cells of the upper aerodigestive tract that line the mucosal surface in the head and neck region. In India, HNC is common in males, and it is the sixth most common cancer globally. Conventionally, HNC attributes to the use of alcohol or chewing tobacco. Over the past four decades, portions of human papillomavirus (HPV)-positive HNC are increasing at an alarming rate. Identification based on the etiological factors and molecular signatures demonstrates that these neoplastic lesions belong to a distinct category that differs in pathological characteristics and therapeutic response. Slow development in HNC therapeutics has resulted in a low 5-year survival rate in the last two decades. Interestingly, HPV-positive HNC has shown better outcomes following conservative treatments and immunotherapies. This raises demand to have a pre-therapy assessment of HPV status to decide the treatment strategy. Moreover, there is no HPV-specific treatment for HPV-positive HNC patients. Accumulating evidence suggests that phytochemicals are promising leads against HNC and show potential as adjuvants to chemoradiotherapy in HNC. However, only a few of these phytochemicals target HPV. The aim of the present article was to collate data on various leading phytochemicals that have shown promising results in the prevention and treatment of HNC in general and HPV-driven HNC. The review explores the possibility of using these leads against HPV-positive tumors as some of the signaling pathways are common. The review also addresses various challenges in the field that prevent their use in clinical settings.

Cytotoxicity Enhancement in MCF-7 Breast Cancer Cells with Depolymerized Chitosan Delivery of α-Mangostin

“…Morphologically, CSNPs are identified by most studies as spherical particles [ 10 , 69 ]. This study showed that the shape of the NPs of CS–LMW and CS–HMW is spherical, as depicted in Figure 3 .…”

“…Because amine groups must have a positive charge, the ZP falls with molecular weight. The PDI was higher in all NPs produced with low MW CS than in high MW CS [ 10 , 41 , 51 , 57 , 59 ]. The presence of free amino groups raised the surface charges and ZP of the NPs, strengthening the electrostatic contacts between the NPs and the drug, maintaining the spherical shape of the beads, and decreasing their size.…”

“…The ongoing quest for better and more efficient chemoprevention and chemotherapeutics is important. Phytochemicals have recently gained expanded interest as chemoprevention and chemotherapeutics [ 9 , 10 , 11 ]. Our previous study shows that AMG, as a natural medicine, is a potential chemopreventive and chemotherapeutic substance used for cancer treatment [ 12 ].…”

JAK/STAT Signaling: Molecular Targets, Therapeutic Opportunities, and Limitations of Targeted Inhibitions in Solid Malignancies

“…The constitutive activation of JAK/STAT signaling is documented in diverse malignancies and is associated with the transactivation of several genes in malignant cells both in vitro and in vivo settings ( Mali, 2015 ). Increasing STAT3 phosphorylation in primary HNC tumors and normal mucosa from HNC patients indicates early STAT3 activation in carcinogenesis ( Aggarwal et al, 2021 ). Furthermore, a study has been performed and reported the increased STAT3 expression in smokeless tobacco-mediated HNC with minimal STAT3 in normal tissues ( Sinevici and O’sullivan, 2016 ).…”

Molecular pathways modulated by phytochemicals in head and neck cancer

“…Anatomically four main regions included in HNC are, the oral cavity, pharynx, nasal cavity, and larynx. Histologically HNC starts with oral precancerous lesions such as, leukoplakia, erythroplakia, and oral submucous fibrosis and malignant tumors like squamous cell carcinoma, adenocarcinoma, lymphoma, and blastoma (Aggarwal et al 2021). Depending on etiological factors HNC can be tobacco‐induced (Pipes, cigarettes, and cigars), alcohol‐induced, or Virus (Human‐papillomavirus and Epstein‐Bar virus) mediated (Hashibe et al 2009).…”