# Role of HIV in acceleration of HPV malignancy

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $368,097

## Abstract

Project summary/Abstract
Accumulating evidence indicates that the incidence of HPV-associated neoplasia in HIV-positive individuals is
substantially higher than in HIV-negative individuals despite effective antiretroviral therapy. These data strongly
suggest that HIV may play a critical role in development of HPV-associated neoplasia of the anus, cervix and
oropharyngeal cavity. However the mechanisms by which it does so are poorly understood. Our published
work and preliminary data show that HIV may interact with oral and anal epithelia creating a tissue
microenvironment where epithelial cells lose tight and adherence junctions. These epithelia have multiple
changes consistent with epithelial-mesenchymal transition (EMT), a multistep epigenetic process characterized
by loss of cell adhesion and increased mobility of epithelial cells. EMT is important in cell differentiation during
embryogenesis but also plays a critical role in neoplastic progression. Our data show that oral and anal
mucosal epithelial biopsies obtained from HIV-infected individuals show typical signs of EMT, i.e., the
adherens junction protein E-cadherin is down-regulated and vimentin expression is up-regulated. Exposure of
tonsil epithelial cells from HIV-uninfected individuals to HIV tat and gp120 proteins leads to induction of EMT.
Additionally we observed that HIV infection is associated with elevation of proinflammatory cytokines tumor
necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) in mucosal epithelia, which may also be involved
in induction of EMT. Finally, it is known that HPV oncoproteins E6/E7 can induce the EMT phenotype. Thus,
there are several pathways through which HIV and HPV may interact with mucosal epithelia, and may
synergize to establish EMT with consequent potentiation of HPV-associated neoplasia. In general the EMT
phenotype is reversible and EMT cells may transition back and forth between EMT and the normal state, a
process known as mesenchymal-epithelial transition (MET). Induction of MET or inhibition of EMT may
represent a novel approach to prevention and treatment of HPV-associated oropharyngeal, cervical and anal
neoplasia and may be a novel approach to reducing the high incidence of HPV-associated malignancy in HIV-
infected individuals. Accordingly, our specific aims are: (1) To investigate mechanisms of HIV-associated EMT
in cervical and anal mucosal epithelial cells and induction of MET in these cells by suppression of vimentin and
upregulation of E-cadherin expression, (2) To investigate synergy between HIV and HPV in development of
the EMT phenotype, and (3) To study the role of suppression of HIV- and HPV- induced EMT and activation of
MET in the reduction of HPV-associated cervical and anal cell transformation and invasion. Knowledge
generated through this work will be of great value to understanding the mechanisms by which HIV and HPV
interact to potentiate development of HPV-associated epithelial neoplasia. This knowledge may al...

## Key facts

- **NIH application ID:** 9815965
- **Project number:** 5R01CA232887-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** SHAROF M TUGIZOV
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $368,097
- **Award type:** 5
- **Project period:** 2018-12-01 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9815965

## Citation

> US National Institutes of Health, RePORTER application 9815965, Role of HIV in acceleration of HPV malignancy (5R01CA232887-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9815965. Licensed CC0.

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