Primary/Secondary Cervical Cancer prevention Flashcards Preview

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Flashcards in Primary/Secondary Cervical Cancer prevention Deck (25):

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)
-LSIL (associated with CIN I)
-HSIL (associated with CIN II-IV)



Atypical squamous cells of undetermined dignificance

- alterations in squamous cells to warrant close clinical attention but not abnormal enough to be LSIL or HSIL



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



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%



- 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



- 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