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Cervical Cancer

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					        Cervical Cancer & Pap Smears


               Joshua D. Stein MS
                 Medical Student
            Jefferson Medical College

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             Epidemiology

• 16,000 cases / year
• Incidence  but mortality from cervical
  cancer  over the past 50 years
• Cervical CA is still the 7th most common
  cancer in females and the 8th most
  common cause of death


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                      Etiology



        •    Human Papiloma Virus (HPV)
            + an unidentified co-carcinogen




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                     Risk Factors
•   Multiple sexual partners (> 1)
•   Promiscuous partner
•   Age of first intercourse experience
•   Early childbearing
•   Prior STDs (HSV II, genital warts, vaginal infections)
•   Cigarette Smoking
•   Oral Contraceptive usage
•   Intrauterine exposure to DES
•   Immunodeficiency

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                 Age of Onset

• Carcinoma In-Stiu (CIS)                    30 years
• Cervical Intraepithelial Neoplasia (CIN)   35 years
• Invasive Cervical Cancer                   45 years




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          Histological Types

 • Squamous Cell Carcinoma 80-95%
 • Adenocarcinoma              5-20%
 • Other: Clear cell, sarcomas




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                      Symptoms

• CIN: Asymptomatic
• Invasive Cancer
        – No classic presentation
        – May present with abnormal vaginal bleeding
        – May present with postcoital bleeding




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                     Physical Exam

• CIN
        – Cervix appears normal to general inspection
• Invasive Cancer
        – Exophytic growth seen on cervix
        – Growth: Cauliflower-like, friable, deeply ulcerated
• Advanced Cancer
        – Pelvic Masses Palpable

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               Metastasis

• Morbidity and Mortality associated with
  regional spread of the cancer
• Spreads to pelvic nodes, ureters, bladder,
  rectum.
• Dangerous when cancer blocks ureters
  resulting in uremia --> death
• Hematogenous spread- uncommon

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                Pathogenesis
• Site where squamous epithelium of vagina meets
  columnar epithelium of endocervix known as
  squamocolumnar junction (SCJ)
• Before puberty: SCJ located just inside the cervical
  os
• At puberty, increasing levels of estrogen lead to
  squamous metaplasia of columnar epithelium to
  squamous epithelium
• Results in repositioning of the SCJ further towards
  the uterus

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                Pathogenesis (2)
• Region between the old and new SCJs known as the
  transformation zone
• Transformation zone is the site of 95% of the cervical
  cancer development
• Since zone is located within the cervical os, unable to
  be viewed during routine pelvic exam
• Exposure of transformation zone to carcinogens
  begins process of intraepithelial neoplasia
• While exact role of carcinogens in this process
  remains poorly understood, it is clear that HPV and
  cigarette smoking can cause dysplasia at the
  transformation zone
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         Human Papiloma Virus (HPV)

• Certain types of HPV are responsible for
  genital warts, others for dysplasia/cancer
• HPV Types 6 & 11
        – associated with development of genital warts
• Types 16,18,31,33,35,39,45,51,52,56,58
        – associated with development of dysplasia/cancer



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                      Pap Smears

• Strong sensitivity and specificity
• Accuracy of Smear Requires
        – adequate sample
        – presence of enough inflamation and dysplasia
        – quick fixation of specimen to glass slide




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            When to Get Pap Smears

• ACOG Recommendations
        – 1st Pap Smear at age when patient becomes
          sexually active (or by age 18)
        – Yearly pap smears thereafter
• Others contend that monogamous women
  with no history of abnormal pap smears
  can have them done every 3 years

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          Performing Pap Smear
• Patient asked to lie on her back at edge of exam
  table with feet in stirrups
• Metal or plastic speculum is inserted into vagina to
  expand the wall of vagina to enable access to cervix
• Cells are collected using cotton swab, wooden
  spatula, or cervical brush and smeared onto glass
  slide
• Preservative sprayed to prevent cells from drying
  and artifacts from forming
• Slide evaluated by lab technician who looks for
  abnormalities in the 50,000 to 300,000 cells on slide
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 Pap Smear Classification Systems

• The Class System (I to V)
• The CIN System (CIN I to III)
        – characterizes the degree of cellular abnormalities
• The SIL System (Bethesda System)
        – Lesions characterized as LGSIL or HGSIL
        – Presence of HPV noted
        – This scheme is most widely used system these
          days
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        Evaluating the Pap Smear

• First, the smear is evaluated for adequacy
  of sample
• Secondly the sample is categorized as
  “normal” or “other”
• Lastly, all sample categorized as “other”
  are further specified as infection,
  inflammation, or various stages of cancer

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        What to Inform Patients Prior to
            Obtaining Pap Smear
• No douching or usage of vaginal
  medications, lubricants, or spermicides
  within 2-3 days of exam (these products
  may hide abnormal cells)
• Schedule Pap Smear between days 12-16
  of menstrual cycle, if possible
• Abstain from intercourse 1-2 days prior to
  smear
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 Pitfalls of Diagnosing Cervical Cancer
• 30% of cases of cervical cancer are missed due
  to errors interpreting results of pap smears
• Ways of Improving Pap Smears
        – rescreen portions of slide deemed negative to
          reduce false-negatives
        – new liquid smears may be have higher sensitivty
          and specificity
        – usage of computerized devices to analyze smear
          (PAPNET, VIRAPAP)

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   Improving Access to Pap Smears

• 50% of patients who die of cervical cancer
  have never had a Pap Smear
• Uninsured, minorities, older patients and
  those who live in rural areas have limited
  access to Pap Smears
• These groups must be targeted to further
  reduce rates of cervical cancer in the US

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           Precursor Lesions
• Reason for thorough classification schemes for
  intraepithelial lesions is to determine the
  likelihood of such lesions progressing to overt
  cancer
• Usual progression from mild dysplasia to overt
  cancer takes 7-8 years
• Precursor lesions characterized as mild
  dysplasia have 65% chance of spontaneously
  regressing, 20% chance of remaining the same,
  15% chance of worsening
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         Precursor Lesions (2)
• Unfortunately, we are unable to predict with
  much accuracy, which lesions will regress and
  which will worsen over time
• For this reason, ACOG recommends any patient
  with a mildly abnormal smear undergo further
  evaluation with culposcopy and/or biopsy




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                Culposcopy
• Culposcope: A stereomicroscope that enables
  investigators to examine areas of dysplasia and
  select best sites to biopsy
• device has green filter that helps identify
  presence of blood vessels (an ominous sign)
• Before culposcopy, cervix coated with acetic
  acid which enhances presence of dysplasia
• Key to culposcopy is complete visualization of
  transformation zone
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                       Cone Biopsy
• Reasons for Performing Cone Biopsy
        – Investigator is unable to visualize the entire
          transformation zone
        – Endocervical curretage shows dysplastic changes
        – Results of Pap Smear are remarkably different than
          results from culposcopy
• Cone biopsy is a minor surgical
  procedure to further investigate the
  transformation zone
• Performed using a scalpel or laser
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                   Treatment of CIN
• Most effective treatment is excision of
  precursor lesions
• Ways to Remove Lesions
        – Cryocautery- freezing, thawing, & refreezing lesion
        – Culposcopic Laser Therapy- more accurate, capable
          of removing low and high grade lesions
        – Excisional Biopsy- performed on low grade lesion
• Always schedule follow-up Pap Smears to
  assure lesions have not returned
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        Managing Cervical Cancer
• All visible lesions should be biopsied
• Lesions must be properly staged to determine
  whether cancer has spread and help determine
  therapeutic approach
• Cervical Cancer spreads by lymphatics or direct
  invasion
• Lymphatic Spread:
    – Cervical/paracervical nodes  regional nodes  deep
      pelvic nodes
    – Direct spread: To bladder, vagina, parametria, rectum
    – CT Scan helpful in assessing cancer that has spread

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 Treatment of Invasive Cervical Cancer

• Option 1: Surgery
        – Useful in patients with Stage I and II cancer
        – Radical hysterectomy is procedure of choice for
          overt cancer
        – When performing surgery, spare ovaries so they
          can continue to manufacture estrogen
        – Potential pitfalls of surgery: hemorrhage, damage
          to nerves supplying bladder, formation of fistula

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         Treatment of Cervical Cancer

• Option 2: Radiation
        – Reserved for poor surgical candidates or patients
          with advanced disease
        – Problems with radiation- infertility, radiation
          cystitis, fibrosis
        – Usually ineffective in patients with recurrent
          cervical cancer



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               Prognosis


• Patients with CIS and cancer limited to
  cervix- cure rate 90-100%
• Patients with advanced cervical cancer-
  cure rate is 25-50%



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Reasons for Such Good Prognosis
      for Cervical Cancer

• Presence of an easily identifiable
  precursor lesion
• Slow progression of cancer
• Access to cheap non-invasive diagnostic
  tools (Pap Smears and Culposcopy)
• Simple and effective treatments

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