News Center

Human papillomaviruses (HPV) are the most common sexually transmitted infection. Ordinarily these infections are resolved by the body’s immune responses, but if the virus evades these, it can lead to multiple health complications such as genital warts and a variety of cancers, including cervical cancer and cancers of the vulva, vagina, penis, anus and throat.

“Over 90% of cervical cancers — and approximately 5% of all cancers — are caused by HPV; there are currently no drugs that target HPV to assist with the alleviation of this disease burden,” said Iain Morgan, Ph.D., member of the Cancer Biology research program at VCU Massey Cancer Center.

To address this gap, Morgan was recently awarded more than $2.8 million in total funding through a five-year R01 grant from the National Institute of Dental and Craniofacial Research to better understand HPV replication and discover new targets and therapeutics that could help prevent or treat HPV-related cancers.

There are more than 100 forms of HPV, of which at least 14 are linked to the development of cancer, including HPV 16, according to the World Health Organization.

“The focus of this grant is to enhance our understanding of the HPV 16 life cycle and how it interacts with the host in order to identify novel therapeutic targets,” said Morgan, who is also chair of oral and craniofacial molecular biology and the director of the Philips Institute for Oral Health Research at the VCU School of Dentistry. “We have previously discovered a novel cellular complex, WRN-SAMHD1-MRN, that controls the HPV 16 life cycle, and we will further investigate the role of this complex in the regulation of HPV replication.”

Morgan’s lab found that WRN restricts the ability of HPV 16 to multiply, and the absence of the WRN and SAMHD1 genes are associated with increased cell proliferation, DNA damage and viral replication. Morgan’s team also observed an abundance of the MUS81 gene at the site of HPV 16 replication in the absence of WRN. These findings suggest that WRN, SAMHD1 and MUS81 could all potentially be manipulated in an effort to block HPV regeneration.

Additionally, Morgan has observed that disrupting WRN or SAMHD1 in HPV 16-positive cells stimulates the host innate immune response; this stimulation would promote the efficacy of existing immunotherapies used to target HPV-positive cancers.

Morgan will collaborate on this research with Pietro Pichierri, Ph.D., a team leader at the Istituto Superiore di Sanita in Rome, Italy. Pichierri will focus on characterizing the host replication complex in HPV16-positive versus negative cells. Differences in the constituents of the host replication complex between the two cell types could potentially help identify a novel therapeutic target to preferentially kill HPV16-positive cancer cells while leaving HPV-negative cells relatively undamaged.

Written by: Blake Belden