Monitoring mouse papillomavirus-associated cancer development using longitudinal Pap smear screening.

Area of Science:

• Gynecologic Oncology
• Virology
• Preclinical Models

Background:

• Cervical cancer remains a risk despite HPV vaccination due to persistent infections.
• Early diagnosis and effective preclinical models are crucial for developing new treatments.
• The mouse papillomavirus 1 (MmuPV1) model offers a relevant system for studying HPV genital pathogenesis.

Purpose of the Study:

• To validate Papanicolaou (Pap) smears as a tool for monitoring disease progression in the MmuPV1 mouse model.
• To assess the utility of Pap smears in detecting cellular abnormalities associated with HPV infection in mice.
• To establish a reliable method for longitudinal disease monitoring in this preclinical model.

Main Methods:

• Biweekly cervicovaginal swabs were collected from MmuPV1-infected mice.
• Swabs were analyzed for viral DNA and assessed using the 2014 Bethesda system for cytological abnormalities.
• Histological and virological assays were performed on harvested tissues.

Main Results:

• Increased viral replication correlated with higher viral DNA levels and increased epithelial cell abnormalities.
• Cytological findings from Pap smears aligned with histological evaluations.
• Mice with squamous cell carcinoma (SCC) cytology developed vaginal SCCs, mirroring human disease stages.

Conclusions:

• Pap smear screening is an effective method for longitudinal monitoring of disease progression in the MmuPV1 mouse model.
• This validated cytology assay supports the development and testing of novel therapies for HPV-associated diseases.
• The MmuPV1 model with Pap smear monitoring shows promise for advancing cervical cancer research and treatment strategies.