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45 Cards in this Set
- Front
- Back
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HPV-related lower genital tract cancers |
High-risk HPV types are: 16, 18, 31, 33, 45. Lower genital tract squamous cell carcinomas - 60% HPV 16, 10% HPV 18 Endocervical adneocarcinomas - mostly HPV 18 Low-risk types (6 and 11) cause condylomas. |
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HPV "pyramid" |
75% of HPV in age 15-24, but only half are high-risk HPV and only 10% persist > 2 years. Only fraction of persistent infections progress towards cancer. |
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HPV Oncogenesis |
Most clear, but 10% persist. Some of these integrate into host genome - necessary step in oncogenesis. |
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Genomics of HPV |
dsDNA, 7900 nucleotides L1, L2 - capsid proteins. Targets of vaccines. E1-E7 - involved with viral transcription and regulation. E6, E7 are oncogenic - interfere with cell cycle regulators - E6 blocks p53, E7 blocks RB. E2 downregulates E6 and E7, but is destroyed when virus integrates. |
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HPV DNA testing |
Can be performed on material from Pap or on biopsies. Test specifically for high risk types, esp HPV 16 and 18. Three accepted uses: 1. ASCUS - atypical cells, used to triage to determine how risky. 2. Ancillary test for woman over 30 - if both Pap- and HPV-, can stretch out screening interval to every 5 years. 3. Primary screening for HPV Never test for low-risk HPV DNA. |
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HPV Vaccines |
Made from non-infectious HPV-like particles (L1 and L2). Not a virus at all. Three IM injections over six months (0, 2, 6) 1. Gardasil 4 - HPV 6, 11, 16, 18 "Quadrivalent vaccine) 2. Cervarix - HPV 16, 18 (Bivalent) 3. Gardasil 9 "Nonavalent" - HPV 6, 11, 16, 18, 31, 33, 45, 52, 58 |
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ACIP Recommendations for HPV Vaccination |
Initiate at age 9-12 for both boys and girls. If not given, catch-up vaccine for men 13-26. |
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Efficacy of HPV vaccine
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Nearly 100% efficacy in preventing precancers and warts by targeted types Does not protect from disease due to HPV types already acquired. No therapeutic effect on HPV-related disease. Duration of protection unclear. |
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HPV vaccine and screening |
Vaccination does not replace other prevention strategies. Routine screening combined with vaccination gives much greater protection. |
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Risk factors for cervical cancer |
HPV-related - Early age at first intercourse - Multiple sexual partners - Increased parity - Male partner with multiple previous sexual partners Host-related - Immunosuppression - Oral contraceptive use - Smoking - Certain HLA types |
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Where do cervical cancers tend to develop? |
Tend to develop in cervical transformation zone (area where transforms from glandular to squamous)
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Squamous lesions of cervix - categories |
LSIL - CIN I (Mild dysplasia) HSIL - CIN II and III (moderate dysplasia, severe dysplasia, and carcinoma in situ) LSIL corresponds to productive/episomal HPV infection; HSIL corresponds to integrated HPV/premalignant lesion. |
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Histological gradi[ng of squamous intraepithelail lesions |
Grade by amount of epithelium replaced by immature cells with increased mitoses, measured in thickness LSIL - <1/3 thickness change HSIL/CIN 2 - 1/3 - 2/3 thickness change HSIL/CIN 3 - > 2/3 thickness change |
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Histology of LSIL/CIN 1 |
Enlargement of cells at base Koilocytes at top - dark nuclei with clear spaces at top which have viral particles |
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Condyloma acuminatum in women - appearance, histology, cause, and location |
Wart - raised, papillary projection above epithelium (instead of flat lesion like LSIL).
Similar histology to LSIL Caused by HPV 6 and 11 Occur in vulva, vaginal, peri-anal and cervix. |
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Marker for integrated HPV
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Downregulated by pRB, so upregulated in integrated HPV when E7 blocks RB. Indicates high-grade lesion that needs treatment. Splits CN2 into LSIL and HSIL (p16+). |
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Natural history of L and H Squamous intraepithelial lesions after 2 years |
LSIL - Regresses 60%, persists 30%. Progresses to HSIL 10% HSIL - Regresses 30%, persists 60%. Progresses to carcinoma 10%. |
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Management of biopsy-proven SIL |
LSIL - Follow with Pap testing HSIL - Excise lesion (in vulva or vagina) or entire transformation zone (cervix) - Loop electrocautery excisional procedure - Cold-knife cone |
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Nomenclature for reporting Paps |
Bethesda system 1. NILM (Negative for Intraepithelial Lesion?Malignancy) - Normal cytoplasm, small nuclei. 2. LSIL 3. HSIL 4. Squamous cell carcinoma 4. ASC (Atypical squamous cells) - ASC-US - Suggestive of but not diagnostic of LSIL - ASC-H - Suggestive of but not diagnostic of HSIL |
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LSIL in bethesda system - cause, histology, behavior, and followup |
Cellular changes due to productive HPV infection Histology - Cells with enlarged, dark nuclei and big halos/caves (koilocytes). Empty spaces are filled by HPV virions. Most regress spontaneously but 15% incidence of CIN III+ (HSIL) in 2 years. HPV testing is not effective triage for these because most are caused by high-risk HPV. Follow-up is colopscopy and biopsy |
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HSIL in Bethesda system - cause, histology, and follow-up |
Encompasses premalignant cellular hanges due to integrated HPV virus Virtually all positive for high-ris HPV Histology - Nuclei are small and dark, but cytoplasm is much smaller (greater nuc:cyt ratio) Follow-up - Coposcopy and biopsy, or go directly to excision procedure like LEEP |
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Squamous cell carcinoma in Bethesda system - histologic features on Pap and management |
Invasion not seen on cytology but certain clues: - Keratinization - Prominent nucleoli - Tumor diathesis - necrotic background material Management: Biopsy, coposcopy, or LEEP. |
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ASC-US in bethesda system - histology, prognosis, and follow-up |
Cellular changes suggestive of LSIL but not diagnostic Nuclei are large, not quite as dark Clearing is not as clear Incidence of HSIL is 8-9% Treatment - If high risk HPV DNA present, 15% risk of HSIL (same as LSIL) - Biopsy, coposcopy If no high risk HPV DNA - treat as LSIL with follow-up Pap. |
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ASC-H in bethesda system - histology, prognosis, and follow-up |
Cellular changes suggestive of HSIL but not diagnostic Higher risk of CIN3+ Follow up - Colopscopy and biopsy, reglrdless of HPV DNA results. |
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Pap smear for glandular abnormalities |
Not an effective screening test for glandular lesions, low sensitivity Glandular lesions seen sometimes though. Complicated management algorithms. |
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Who needs a Pap test? When to stop? |
- Age 21 and over, every 3 years - After age 30, remains every 3 years. Every 5 years if HPV DNA co-testing - More often (annually) if high risk - immunosuppression, HIV, history of prior cancers or pre-cancers. Stop if woman over 65 with adequate prior negative testing, and hysterectomy for benign disease. |
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False negative rate of Pap tests |
Significant - 15-25% Regular screening is key to effectiveness |
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Squamous cell carcinoma of female reproductive tract - location and common cause |
Most common malignancy in cervix, vulva. Rare in vagina. Involves invasion through basement membrane. HPV-related: - 100% cervical SCC - About 50% of vaginal or vulvar SCC |
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Superficially invasive SCC and implication |
If SCC is minimally invasive, treat it less aggressively. Just do LEEP. |
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Cervical adenocarcinoma - cause, diagnosis, presentation, and prognosis |
Incidence increasing. Due to HPV-18, most commonly. Difficult to diagnose. Pap test is not sensitive enough, so present at higher stage. Clinically - Abnormal mucinous discharge, post-coital bleeding and spotting, enlarged, barrel-shaped cervix
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Precursor to cervical adenocarcinoma - and age, histology, and cause |
Adenocarcinoma in situ Mean age of 39 Histology: - Tall, hyperchromatic, crowded nuclei with little cytoplasm - Mitotic activity - Apoptotic bodies - p16+ 50% or more co-exist with squamous HSIL. Caused by HPV 18 > 16. |
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Benign and malignant pathologies of cervix |
Benign- Endocervical polyp - sometimesi cause sbleeding and must be biopsies Malignancies- Adenocarcinoma |
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Endocervical polyp - clinical presentation and pathology |
Common, benign polypoid mass Clinical: Bleeding/spotting, often asymptomatic Pathology: - Normal endocervical glands - Squamous metaplasia common - Ulceratoin common - Large vessels in stroma |
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Benign and malignant pathologies of vagina |
Benign: - Gartner duct cyst - Fibroepithelial polyp Malignant: - SCC - Embryonal rhabdomyosarcoma |
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Gartner duct cyst - source, and histology |
Benign pathology of vagina. Common Derived from Wolffian duct remnants Cyst lining benign glandular cells |
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Fibroeoitehlalil Polyp of vagina - age, histology |
Common in vulva, vagina Any age, but tend to occur in pregnant women Histology: Polypoid masses with benign squamous lining and benign stroma Often has multinucleated stromal giant cells |
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Most common vaginal sarcoma |
Embryonal rhabdomyosarcoma - still very rare Mostly occurs in girls under 5 years. Highly aggressive, good cure rate with chemotherapy
- Normal squamous epithelium - Cambium layer with mitotic activity - Empty, hypocellular area |
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Pathologies of Vulva |
Dermatoses: - Lichen sclerosis - Lichen simplex chronicus Bartholin's duct lesions Malignancies - Squamous cell carcinoma - Paget's disease |
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Lichen sclerosus |
Thinning of epithelium of vulva with homogenous collagen lying underneath it Most common in postmenopausal women Etiology unclear. |
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Lichen simplex chronicus - cause, histology, presentation |
Histology: Squamous hyperplasia - thickening of vulval skin
Treatment: Manifestation of rubbing or scratching. Try to identify and treat cause - commonly yeast infection. |
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Bartholin's duct lesions - age, histology, and treatment |
Paired glands with ducts opening at vaginal introitus 1. Cysts secondary to duct obstruction Any age Histology: Lined by glandular (ductal) cell sor metaplastic squamous cells Treat - Excision or marsupialization (open it up) 2. Abscess secondary to infection/blockage. |
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Vulvar Squamous Cell Carcinoma - comparing HPV vs non-HPV in population, precursor, history, and appearance |
HPV-related - Younger patients - Precursor off HSIL - Basaloid, warty appearance Non-HPV-related - Older - Clinical history of Lichen sclerosis, often - Precursor of differentiated VIN - Appearance: Well-differentiated, keratinized |
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Differentiated VIN - background and histology |
1-4% with Lichen Sclerosis develop vulvar cancer Arises from non HPV-associated differentiated VIN Histology: Surface epithelium look normal. Very pink Base has large, atypical nuclei. |
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Paget's Disease of Vulva - presentation, background state, prognosis |
1% of vulvar cancer Presentation: Eczematous plaque with itching, often mistaken for candiida Underlying carcinoma in 25% Frequent recurrence because hard to get around margins Good overall prognosis Must rule out melanoma |
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Histology of Paget's DIsease
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Histology: - Nests of glandular cells in squamous epithelium (not stroma) - May see mucin droplets, gland formation |
