Exam 4 - HPV Flashcards
What are the relative incidence and mortality of cervical cancer in developed vs. developing countries?
<3 per 100,000 in developed countries
> 16 per 100,000 in some of the least developed countries
What ethnic/racial groups are at the highest risk for cervical cancer (incidence and mortality)?
highest incidence in American Indian/Alaskan native and hispanic
highest mortality in black and hispanic
Why is it significant that the CDC data show cervical cancer is not a top 10 cancer or cause of death in the US?
the US is doing something right to prevent cervical cancer
What is the structure of HPV (genetically, proteins, etc.)
- double stranded circular DNA episome
- surrounded by 72 pentameric (5 sided) capsids
- each capsid is a viral protein
- L1 and L2 genes encode for capsid proteins
individual capsids will assemble into virus like particles (VLPs) when expressed in microbial organisms - each type of HPV has a unique capsid protein
What is an oncogene?
genes that cause transformation of normal cells into cancerous tumor cells, especially viral genes that transform host cells into tumor cells
What types of HPV are oncogenic and non oncogenic? What diseases are associated with different classifications?
HPV 16 accounts for nearly 50-60% of all cervical cancer
HPV 18 accounts for 10-20% of cervical cancers
HPV 6 and 11 are associated with 90% of genital warts
Describe the important anatomy of the cervix in relation to HPV and cervical cancer
cervix has flat squamous cells in the transition zone (the region near the vagina)
Define squamous, dysplasia, carcinoma, and malignant neoplasm?
squamous - plate like, thin, flat
dysplasia - alteration in size, shape, and organization of adult cells
carcinoma in situ - abnormal cells have not spread beyond where they first formed
invasive cancer / malignant neoplasm - abnormal cells tending to infiltrate surrounding tissues
Describe the progression of mild/moderate dysplasia to moderate/severe dysplasia to invasive cancer
infection with HPV (80% cleared without treatment)
20% advances to LSIL (mild to moderate dysplasia), 80% of which clears and 20% advances to HSIL (moderate to severe dysplasia)
20% of HSIL advances to invasive cervical cancer
average time from infection to invasive cervical cancer is 15 years
Why doesn’t all HPV infection lead to cervical cancer?
80% of infections resolve without treatment and HPV becomes undetectable in the cervix
generally resolves without any intervention within 18-24 months
How does HPV infection progress to cervical cancer at the molecular level?
- HPV accesses basal cells through micro-abrasions of the cervical epithelium
- early HPV genes (E1-7) are expressed and viral DNA replicates from episomal DNA, not integrated into the nuclear DNA
- in upper layers (midzone and superficial zone) of the epithelium, viral genome is replicated and L1 and L2 are expressed
- L1 and L2 encapsidate the viral genome to form progeny virons in the nucleus
- shed virus can initiate new infection
- low grade intraepithelial lesions support productive viral replication
- high risk HPV infections progress to high grade cervical intraepithelial neoplasia (HSIL)
- progression of untreated lesions to invasive cancer is associated with integration of HPV genome into the host chromosomes (and up regulation of E6 and E7 oncogenes)
At what are are most women exposed to transient HPV infection?
teens and 20s
At what age is the peak prevalence of cervical precancerous conditions observed?
about 10 years later, so 20s and 30s
At what age is the peak prevalence of invasive cervical cancer observed?
40-50 years of age
Explain the timing of screening for cervical cancer and the types of screenings performed?
pap tests start at about 21 to look for cytologic changes, new strategies include HPV screenings at peak ages of treatable precancerous conditions and early cancer (about age 35 and 40)
