Cervical Cancer

1
Cervical Cancer Pap Smears

• Joshua D. Stein MS
• Medical Student
• Jefferson Medical College

2
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

3
Etiology

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

4
Risk Factors

• Multiple sexual partners (gt 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

5
Age of Onset

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

6
Histological Types

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

7
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 --gt death
• Hematogenous spread- uncommon

10
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

21
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