HPV

Question 1

Cervical Cancer Statistics

Answer 1

• 10% of female cancers diagnosed worldwide are cancers of the cervix
• Cervical cancer is most commonly diagnosed cancer among women in Southern Africa and Central America
• Cervical cancer is the 2^nd most common cause of cancer-related death for women world-wide

Question 2

Incidence, Prevalence and Mortality

Answer 2

• Incidence- rate at which new cases are diagnosed in population during a specific period
• Prevalence- proportion of population affected by disease at a specific time
• Mortality- rate at which individuals die from a disease

Question 3

Malignant Neoplasm

Answer 3

• Tumor that tends to grow, invade, and metastasize
• 2^nd leading cause of death in women in U.S.
• Of malignant neoplasms, cervical cancer:
  
  • is in the top 10 for incidence only in Blacks and Hispanics
  • Not in the top 10 for death rate among any race

Question 4

HPV

Answer 4

• Human papillomavirus
• Double-stranded circular DNA episome
• Surrounded by 72 penatmeric 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
• VLPs lack viral DNA

Question 5

Types of HPV

Answer 5

• Oncogene- gene that causes transformation of normal cells into cancerous tumor cells, especially a viral gene that transforms a host cell into tumor cell
• HPV 16 accounts for nearly 60% of all cervical cancer
• HPV18 accounts for 10-20% of all cervical cancers
• HPV 6 and 11 are associated with 90% of genital warts

Question 6

Oncogenic HPV

Answer 6

• Affect anal and genital areas
• About 40 types
• High risk
  
  • 30 types (16,18, 31, 33, 45, 52, 58, 59)
  • Low-High grade cervical changes
  • Anogenital cancers
• Low risk
  
  • Genital warts
  • Respiratory papillomas

Question 7

Female Anatomy

Answer 7

• Cervix separates uterus from vagina
• Cervix has flat squamous cells in region near vagina
• Squamous- plate like, thin, and flat
• Dysplasia- alteration in size, shape, and organization of adult cells
• Carcinoma- malignant new growth made up of epithelial cells tending to infiltrate surrounding tissues

Question 8

Cytology of Cervix

Question 9

HPV Clearance

Answer 9

• HPV infection doesn’t always lead to cervical cancer
• 80% of infections are transient, asymptomatic, and resolve without treatment and HPV is no longer detectable in cervix
• In women with intact immune systems, HPV infection generally resolves without intervention within 18-24 months
• LSIL- low grade squamous intraepithelial lesion- mild dysplasia
• HSIL- high grade squamous intraepithelial lesion- moderate to severe dysplasia
• Average time from infection to invasive cervical cancer is 15 years

Question 10

HPV-mediated progression to cervical cancer (1-5)

Answer 10

1. Basal cells in cervical epithelium rest on basement membrane
   
   • Basal cells divide and migrate toward superficial zone
2. Sexually transmitted HPV is thought to access basal cells through micro-abrasions in cervical epithelium
3. Following infection, early HPV genes (E1, E2, E4, E5, E6, and E7) are expressed and viral DNA replicates from episomal DNA (not integrated into nuclear DNA)
4. In upper layers of epithelium (midzone and superficial zone) viral genome is replicated further, and late genes (L1 and L2) are expressed
5. L1 and L2 encapsidate viral genomes to form progeny virions in nucleus

Question 11

HPV-mediated progression to cervical cancer (6-9)

Answer 11

1. Shed virus can then initiate a new infection
2. Low-grade intraepithelial lesions support productive viral replication
3. Unknown number of high-risk HPV infections progress to high grade cervical intraepithelial neoplasia (HSIL)
4. Progression of untreated lesions to invasive cancer is associated with integration of HPV genome into host chromosomes with subsequent up regulation of E6 and E7 oncogene expression

Question 12

Prevalence of HPV

Answer 12

• Peak prevalence of transient infections with carcinogenic types of HPV occur among women during their teens and 20s, after initiation of sexual activity
• Peak prevalence of cervical cancer occurs 10 years later
• Peak prevalence of invasive cencers occur at 40 to 50 years old
• 36% of women <25 re positive for HPV
• Up to 70% of sexually active college-age students are HPV infected
• Only 3% of women >45 are positive for HPV

Question 13

Prevention of Progression

Answer 13

• Conventional model of cervical-cancer prevention is based on repeated rounds of cytologic emanation, including Pap smears
• Alternative strategies include HPV vaccination of adolescents, one or two rounds of HPV screening at the peak ages of treatable precancerous conditions and early cancer, or both

Question 14

Pap Test

Answer 14

• Screening test to detect premalignant and malignant cells in cervix
• Invented by and named after Dr. Georgios Papanikolaou
• Cells are collected for outer opening of cervix
• Cells are placed on glass slide and checked for abnormalities under microscope

Question 15

Pap Histology

Question 16

HPV DNA test

Answer 16

• Can usually be run by lab on same sample of cells used for Pap
• Uses molecular technology to detect presence of high-risk types of HPV
• More effective that Pap smear

Question 17

Flashlight Vinegar Test

Answer 17

• Heath workers look at cervix with flashlight and swabs it with vinegar
• Spot that turns white may be precancerous lesion
• Flashlight lest isn’t much more effective than no screening at all

Question 18

Treatment for abnormal Pap

Answer 18

• Low grade squamous intraepithelial lesion does not require treatment in younger women since it usually goes away by itself
• If LSIL persists or progresses to HSIL:
  
  • LEEP-
    
    • Loop electrosurgical excision procedure
    • Thin wire loop that carrying electric current is used to remove abnormal areas of cervis
  • Cryotherapy
    
    • Abnormal tissue is frozen and later shed by the body

Question 19

HPV Vaccine

Answer 19

• HPV capsid proteins can assemble into virus-like particles (VLP)
  
  • VLP lack viral DNA and cannot cause infection
• Specific HPV VLPs elicit robust antibody response
  
  • Antibody response will be specific to HPV type
• Gardasil includes VLPs from HPV 16, 18, 6, and 11
  
  • It is quadravalent
• L1 and L2 genes encode for capsid proteins
• Individual capsids will assemble into VLPs when expressed in microbial organism
• VLPs lack viral DNA

Question 20

Who should get HPV vaccine: June 2006

Answer 20

• FDA approved Gardasil for females 9-26 years old
• Recommended prior to onset of sexual activity
  
  • 7.4% of US youth have intercourse by 13
  • 46.7% have intercourse by Grade 12
• Recommended after onset of sexual activity, even if there has been abnormal Pap or HPV DNA test or genital warts
  
  • Vaccination can protect against HPV types not already acquired
• Recommended for immune-suppressed women due to high risk for persistent HPV infection
• Not recommended as newborn immunization because duration period I unclear

Question 21

Who should get HPV vaccine: October 2009

Answer 21

• FDA approved Gardasil for males 9-26 years
  
  • For prevention of genital warts due to HPV types 6 and 11
• Only 1% of sexually active US males develop genital warts, which can be irritating but aren’t life threatening
• Boys are not prone to HPV-related cancers, but are involved in transmission of HPV

Question 22

Controversy

Answer 22

• Should HPV vaccine be mandated?
  
  • Should parent be forced to vaccinate their children
    
    • Does the vaccine encourage sexual activity among young people?
  • Who should cover cost of mandated vaccination?
    
    • Gardasil 3-shot regimen casts about $390