Abstract
Mucosal infection by the human papillomavirus (HPV) is responsible for a growing number of malignancies, predominantly represented by cervical cancer and oropharyngeal squamous cell carcinoma. Because of the prevalence of the virus, persistence of infection, and long latency period, novel and low-cost methods are needed for effective population level screening and monitoring. We review established methods for screening of cervical and oral cancer as well as commercially-available techniques for detection of HPV DNA. We then describe the ongoing development of microfluidic nucleic acid-based biosensors to evaluate circulating host microRNAs that are produced in response to an oncogenic HPV infection. The goal is to develop an ideal screening platform that is low-cost, portable, and easy to use, with appropriate signal stability, sensitivity and specificity. Advances in technologies for sample lysis, pre-treatment and concentration, and multiplexed nucleic acid detection are provided. Continued development of these devices provides opportunities for cancer screening in low resource settings, for point-of-care diagnostics and self-screening, and for monitoring response to vaccination or surgical treatment.
Highlights
40%–80% of oropharyngeal squamous cell carcinoma (OPSCC) diagnosed in the U.S and 18% of OPSCC worldwide contain human papillomavirus (HPV) [19,20], and numerous studies support a viral etiology for oral cancer in these sites [21,22,23,24,25]
It has been postulated that the common endodermal origin of the squamous lining of both the cervix and tonsils, their shared locations at the junction between external and internal environments, and the human microbiota at these mucosal surfaces play a role in enabling persistent HPV infection, providing a favorable milieu for carcinogenesis [27]
Of the millions of people with an HPV infection, most will not develop cancer, but given the millions of young men and women harboring oral HPV and the positive clinical outcomes associated with early detection, development and validation of a technically and conceptually novel multi-target nucleic acid sensor platform for early detection of HPV-associated OPSCC is warranted
Summary
Cervical cancer is the third leading cause of cancer death among women, with. U.S incidence of HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). Head and neck squamous cell carcinoma (HNSCC), which includes tumors of the oral cavity, larynx and oropharynx, is the 6th most prevalent cancer worldwide, representing a major global health problem, with >400,000 cases and >200,000 deaths annually [17]. 40%–80% of OPSCC diagnosed in the U.S and 18% of OPSCC worldwide contain HPV [19,20], and numerous studies support a viral etiology for oral cancer in these sites [21,22,23,24,25]. Most HPV positive oral tumors arise deep within the crypts of the tonsils, are obscured from gross visualization, and often present with lymph node metastases [26], further supporting the need for new screening modalities that can detect HPV-associated disease in biological samples
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