Primary/Secondary Cervical Cancer prevention Flashcards
General trend in HPV screening recommendations
- initial screening at progressively later ages
- introduce new technologies (test for high risk HPV types)
- progressive lengthening of recommended baseline screening intervals
2013 ACS recommendations for cervical cancer screening
- Screen starting at age 21
- Cytology every 3 years between ages of 21 and 29
- Cytology with HPV co-test every 5 years between 30-65
- stop cervical cytology at 65 if adequately screened and not had CIN 2 or CIN 3 lesions for previous 20 years
Cytology screening
- 2 main categories: slide-based and liquid-based
Slide-based: fix sample of cervical cells on slide and send to lab
liquid-based: immerse collection in small vial and send to lab
histology= gold standard against which cytology is measured. Sensitivity/specificity of liquid-based higher than slide-based
Where do you collect your cervical cell sample
Need to include cells from both sides of squamo-columnar junction-
- premalignant squamous lesions of cervix almost always originate at this junction, so sample must include both squamous and columnar cells to be interpreted
normal apperance of cells on pap
- stratified sq epithelium 8-12 cell layers thick
- Superficial squamous cells have abundant cytoplasm with dark pyknotic nucleus
- Endo-cervical– may appear in “honeycomb” array, with distinct cell membranes due to cytplasmic mucin
HPV co-testing
use in women > 30 to assess for high risk HPV strains
Main categories of cervical dysplasia
Patten (Histology: Mild dysplasia, moderate dysplasia, severe dysplasia, Carcinoma in situ
Richart (histology): CIN (grade I), CIN II, CIN III, CIN IV
Bethesda (cytology)
- AGUS
- ASC-US
- ASC-H
- LSIL (associated with CIN I)
- HSIL (associated with CIN II-IV)
ASC-US
Atypical squamous cells of undetermined dignificance
- alterations in squamous cells to warrant close clinical attention but not abnormal enough to be LSIL or HSIL
LSIL
cells with unequivocal evidence of HPV infection (perinuclear cytoplasmic clearing)–attributed to aggregation of virally derived proteins around nucleus
- may have markedly enlarged hyper-chromatic nuclei with an abnormal chromatin distribution, irregular nuclear contour, abundant cytoplasm
HSIL
changes thought to represent presence of significant premalignant lesion. Higher nuclear to cytoplasmic ratio than LSIL
CINII– moderate dysplasia
CIN III- severe dysplasia and carcinoma in situ
What is the chance of progression of SIL
about 25% of all grades of SIL progress to higher grade lesions; of these, about 10% progress to carcinoma in situ and 1% to invasive cancer
Histology of cervix
- basal cells cuboidal and they become progressively flattened as they reach surface with small nucleus. Superficial cells are collected during Pap
- with CIN I-III, you lose that progression so that the cells look the same from bottom to top (high nuclear to cytoplasmic ratio)
HPV association with cervical cancer
- considered necessary but not sufficient precursor to msot cervical dysplasia/carcinoma
- associated with most cases of invasive squamous cell carcinoma, LSIL, HSIL, endo-cervical adenocarcinoma
- most common STD in America, with lifetime risk about 80% for sexually active individuals
- about half of new infections in 15-24 year olds
- In general population, prevalence is 15%
- infection cleared most of the time in 1-3 years. Those present >1 year associated with increased risk of progression to cervical dysplasia
HPV types
- lots of types but GENERALLY
Low risk: 6, 11 (31, 33, 45)- responsible for about 90T of genital warts
High risk: 16, 18–responsible for about 70% cervical cancers
- can use a HPV test screen for 13 of most common high risk types but can’t tell you specific strain
- another test only for 16/18 (Cervista assay)
Management of abnormal screening
- depends on pt age, degree of abnormality on current screen, recent screening/treatemnt hx, and pregnancy status
RISK OF CIN III in next 5 yrs:
- 5%: refer for colposcopy
Management of abnormal biopsy
- depends on age, current screen, recent screening/treatment hx, pregnancy status
- if therapy indicated treat entire transition zone: cryotherapy, laser ablation, excision
- success rates as high as 95%
Gardasil
- HPV vaccine approved in 2006
- quadrivalent: 6, 11, 16, 18 virus-like particle (subunit)
- series of 3 doses at 0, 2, 6 months for women between 9 and 26
- efficacy of 98.8% in trails of reduction of genital warts, CIN2, CIN3 and adenocarcinoma in situ among women naiive to 4 subtypes
Cervarix
- bivalent vaccine covers HPV 16/18
- approved 2009
- 3 doses (0, 2, 6 months)
efficacy of HPV vaccine
- quadrivalent better for disease related to HPV 6/11 but bivalent appears more effective preventing disease attributable to viral types not covered by vaccine (i.e. HPV 31 and 45)
- goal to give all 3 doses prior to sexual activity
Gardasil -9
9-valent vaccine recently approved adds protection against 31, 33, 45, 52, 48, hoping to prevent 90% of cervical cancer.
Acceptance of vaccine
- relatively good receptance among physicians
- variable rates of parental acceptance; less likely in eclectic subgroups
- CDC study: about 25% didn’t intend to vaccinate daughters in next 12 months
- top 5 reasons parents wouldnt vaccinate in next 12 months– not needed, vaccine not recommended, vaccine safety concerns, lack of knowledge about vaccine/disease, daughter not sexually active
- lower rates in boys
- generally well accepted in young adults (college ages)–higher when cover HPV 6/11
Predicted economic impact of vaccine
first positive peak for genital warts and second for CIN, third/final peak for cervical cancer reduction about 30 years into vaccination program
HPV vaccine impact on men
- helps reduce genital warts, anal/penile/OP cancers
- about 25% squamous cell OP cancers assciated with HPV
- possible risk reduction for penile/anile cancers
- herd immunity– will decrease female disease
- immunologic responses similar to women
- CIP recommend vaccination for boys 9026 with quadrivalent vaccine
Vaccine in developing world
- burden of HPV_related dz larger than in developed world
- cervical cancer single largest cause of years of life lost from cancer in developing world
- Cost! very expensive- look at ways to reduce
- hard to administer especially 3 separate times, esp with variable school attendance
- prevalence rates for various types different, so various impact
- governments likely to prioritize vaccinations for food, water, and airborne illnesses instead of cervical cancer
HPV vaccination in HIV infected individuals
- benefit being researched
- potential difference in vaccination strategies with those born with HIV vs getting later in life.
- Issues: point in HIV infection when vaccinated, preexisting exposure to HPV, viral load, CD4 count, potential role of highly active antiretroviral therapy
- study in south africa showed promising results, equivalent immune responses regardless of HIV status, CD4 count viral load, and use of anti-retroviral therapy with no big impact on HIV dz measured by viral load or CD4 count
