Cervical Cancer: Molecular Impact of an Infectious Disease

HPV-16 E6 and E7 genes interact with cell cycle machinery

Background Worldwide, cervical cancer is the 2nd leading cause of cancer death in women Most cervical cancer is either squamous cell (85%) or adenocarcinoma (12%) Risk factors for squamous cell cancer –Early coitarche –Greater than 6-8 partners –Cigarette smoking –Oral contraceptives

During the sexual lifespan of a woman, approximately 70% will have been exposed to HPV The vast majority of HPV infections will regress Primary prevention is not utilized –Stigma –High prevalence –Easy transmission

Cervical cancer is most strongly associated with sexually transmitted HPV infection HPV is endemic among sexually active humans HPV subtypes are classified into high and low risk groups

Progressive infection of Washington State University females with Human Papilloma Virus over time

Progressive infection over time with HPV in college age population measured from time of first intercourse

HPV sub-types in genital infection in female WSU cohort

Current management of cervical cancer is based on detection of disease-secondary prevention Papanicolaou technique for detection is flawed –Acquisition error –Preparation error –Interpretation error –Patient error –Reporting error

Common reasons for presentation –Abnormal vaginal bleeding, esp following intercourse (57%) –Abnormal pap smear (28%) –Low abdominal pain (9%) –Vaginal discharge (4%)

Normal transitioning to dysplastic epithelium in cervix, With accompanying inflammation due to poor barrier function

Squamous dysplasia

Future Topicals –Retinoids –Difluormethylornithine Development of prophylactic and therapeutic vaccines –VLP(L1/L2) –E6/E7