Cervical Cancer Screening

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Cervical Cancer Screening

• UNC Internal Medicine
• Cristin M. Colford, MD
• July, 2008

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This is why I am doing this talk.

• Sent Wednesday, July 02, 2008 1124 PMTo
  Colford, CristinSubject Questions
• Hey Cristin,There is another thing. I just
  learned from my Intern friends that I might have
  to do some Pap-smears? Well that was something I
  did once at Med school but never since then. I
  hope in that case I can always ask a female
  attending (i.e. you?) otherwise I would say the
  patient is better of with a gyn/obst
  consult.Thank you in advance,
• Dr. Intern

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Cervical Cancer

• Second most common cancer in developing countries
• 90 squamous cell, 10 adenocarcinoma
• Incidence has decreased by 70 over last 50 years
  with introduction of the papanicalou screening
  test.
• 11,070 cases of invasive cervical cancer will be
  diagnosed in 2008
• 3,870 women will die of cervical cancer in 2008
• Death rates from cervical cancer decline by 4
  per year

American Cancer Society, 2008
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HPV

• Most common sexually transmitted infection
• Risk factors include young age (lt25,), increased
  number of sex partners, early age at first
  intercourse, male partner with multiple partners
• 20 million Americans aged 15-49 infected
• Half of those infected are sexually active young
  adults ages 15-24
• 5-30 are infected with multiple types of HPV

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Human Papillomavirus

• DNA tumor virus
• 100 types, 40 types infect mucosal surfaces
• Low risk6,11,40,42,43,54,61,72,73,81
• HPV 6, 11 most commonly found in genital warts
• High risk16, 18, 31, 33, 35, 39, 51, 52, 56, 58,
  59, 58, 82
• HPV 16 accounts for almost half of cervical
  cancers
• HPV 18 accounts for 10-12 of cervical cancers,
  including glandular cancers

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HPV

• Prevalence of HPV among cervical cancers is 99
• Most HPV infections resolve spontaneously
• Persistence of oncogenic HPV can lead to
  progression to high grade preinvasive cervical
  lesion or cervical cancer

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Characteristics of women with newly diagnosed
cervical cancer

• 50 have never had a pap
• 10 have not had a pap in 5 years
• Mean age of newly diagnosed cervical cancer in
  the US is 47
• Mortality rate from cervical cancer among African
  American women is more than twice the national
  average

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Cervical Cancer Screening Guidelines

• United States Preventative Services Task Force
• American College of Obstetrics and Gynecology
• American Cancer Society

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United States Preventive Services Task Force

• Strongly recommends screening for cervical cancer
  in women who have been sexually active and have a
  cervix
• Start within 3 years of the onset of sexual
  activity or age 21
• Screen at least every 3 years
• Insufficient evidence to recommend for or against
  liquid based cytology
• Insufficient evidence to recommend for or against
  HPV testing for primary prevention
• Recommends against routinely screening women over
  age 65 if they have had adequate recent screening
  with normal pap smears and are not otherwise at
  high risk for cervical cancer
• Recommends against routine PAP smear screening in
  women who have a total hysterectomy for benign
  disease

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American Cancer Society and ACOG

• Recommend screening for cervical cancer within
  three years of onset of vaginal intercourse or
  age 21, whichever is first
• Conventional PAP Yearly screening age lt 30
  every 2-3 years age gt30 and 3 consecutive neg
  paps
• Liquid based pap every 2 years if lt30, every
  2-3 yrs if gt30 and 3 neg
• Combine negative pap with negative HPV every 3
  years
• Recommend stopping screening in women over age 70
  with 3 consecutive normal paps and no abnormals
  in last 10 years
• Recommend against routine paps in women after
  hysterectomy for benign reasons with no history
  of CIN

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Specimen adequacy

• Pathologist will review slides and determine if
  the specimen is adequate for review.
• Factors include thickness of preparation, drying
  artifact, blood or inflammation
• Pathologists will determine if endocervical cells
  are present

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Endocervical cells

• Indicates adequate sampling of transformation
  zone
• What to do if there are no endocervical cells
  present?
• Some data indicates that detection of epithelial
  abnormalities is higher in samples with
  endocervical cells
• Dutch study showed lower prevalence of squamous
  lesions in follow up of patients with negative
  endocervical cells compared to those with
  presence of endocervical cells

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Endocervical Cells

• Dutch population screening program abolished
  repeat of negative endocervical cell smears
• Task force addressing this issue recommended that
  most women without an endocervical/transformation
  zone component present could be screened with a
  repeat test at routine interval
• However, repeat testing in six months was advised
  in higher risk situations Previous ASCUS
  without three negative paps
• A previous PAP with unexplained glandular
  abnormality HPV test result positive for high
  risk type in previous yr Immunosuppression Insu
  fficient frequency of previous screening

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Cervical cancer screening rates in our clinic-
Leslie Proctor Chart Review

• 167 female patients from 3 providers (male
  resident, female resident and 1 attending)
• Ages 18-91
• 37 had a PAP at UNC in last 3 years
• Accounting for documented hysterectomies and
  outside PAPs
• 40 had PAP in last 3 years

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Chart Review of 197 patients 2002-2004 by Stacey
Sheridan

• 55 of females had a pap smear

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Behavioral Risk Factor Surveillance System

• 2006 survey
• 86 of women in NC reported having had a PAP in
  the last 3 years
• 84 of women nationwide reported having had a pap
  in the last 3 years

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Cervical Cytology

• PAP smear
• We use conventional technique
• Wood spatula, cytobrush on slide
• Studies show that you can use gel lubricant and
  it will not interfere with pap results
• Notice I will not show technique for bimanual
  exam
• No evidence that bimanual exam is an effective
  screening for ovarian cancer in asymptomatic
  patient
• Make sure you do a bimanual when indicated
• Pelvic or abdominal pain, cervicitis, etc.
• Lets review how to do a pap smear.
• http//content.nejm.org.libproxy.lib.unc.edu/cgi/v
  ideo/356/26/e26/

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Cervical Cytology

• In our clinic, we routinely use conventional PAPs
  
• Wooden spatula and brush directly onto slide and
  fixed at bedside
• Liquid or Conventional PAP?
• 80 of paps nationally are liquid based
• 95 of paps at UNC are liquid based
• Are liquid based really better?
• New data emerging

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RCT Accuracy of liquid based compared to
conventional paps Ronco et al. BMJ 5/2007

• 44, 000 women aged 25-60 randomly assigned to
  conventional pap vs liquid based with HPV
  testing.
• Outcome Relative sensitivity for CIN 2 or
  higher with PAP result of ASCUS or higher
  considered positive
• Results No significant difference in
  sensitivity for detecting CIN 2 or greater.
• Liquid based detected more CIN 1 or more lesions,
  but not CIN 3 or more.
• Reduction in unsatisfactory cytology with liquid
  based

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Meta-analysis Liquid compared to conventional
cytology Arbyn et al. Obstet Gyn 2008

• Meta-analysis of seven studies that compared
  liquid to conventional pap using gold standard of
  colposcopy concludes that liquid based compared
  to conventional cytology revealed no
  statistically significant difference in se or sp.
  Except lower sp in liquid based with ascus.
• HSIL
• Liquid based se 57.1 Sp 97
• Conventional se 55.2, sp 96.7
• LGSIL
• Liquid based se 79.1, sp 78.8
• Conventional se 75.6, sp 81.2
• ASCUS
• Liquid based se 90.4, sp 64.6
• Conventional se 88.2, sp 71.3

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What to do with an abnormal PAP?

• ASCUS
• LGSIL
• HGSIL

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Atypical Squamous Cells of Undetermined
Significance

• 2 million paps yearly
• Of patients with cytology finding of ASCUS
• 80.5 had normal biopsy
• 12.8 had Grade 1 CIN
• 6.6 had Grade 2 CIN
• 0.1 had Invasive Cancer

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Options for Management of ASCUS

• Repeat cytology (6 months)
• Immediate colposcopy
• Reflexive HPV DNA testing

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Reflex HPV testing with ASCUS

• ASCUS-LSIL Triage Study (ATLS)
• Determined that Reflex HPV compared to repeating
  PAP had equivalent sensitivity and slightly
  increased specificity.
• If high risk HPV detected, refer for colposcopy
• If no high risk HPV detected, return to routine
  screening interval
• Reduce number of women undergoing colposcopy by
  identifying high risk patients
• Reduce costs, reduce patient anxiety

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Refer for immediate colpo

• LGSIL
• HGSIL

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HPV testing for primary screening

• Offered as an option by ACOG and ACS
• If no high risk HPV and normal PAP, then they
  feel safe to extend interval to 3 years in women
  older than 30

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Canadian Cervical Cancer Screening trial HPV
testing for primary screening NEJM Oct 2007

• Women ages 30-69 presenting for routine
  screening, community setting
• Refer to colposcopy for positive pap, positive
  HPV test or randomly selected from normal results
• HPV testing higher sens (97.4 vs 56.4) but
  lower sensitivity (94 vs. 97)

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HPV testing for primary screening?

• If reduced specificity, then more women referred
  to colposcopy thus increasing costs
• At what interval should test be repeated?
• Cost effectiveness
• Relatively few cases of cervical cancer yearly in
  US
• HPV testing expensive and increase in colpo
  expensive
• Not ready for prime time yet

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Cases

• 54 year old woman presents requesting cervical
  cancer screening. She had a complete hysterectomy
  for fibroids at age 37. Would you perform a pap
  smear?
• A 36 year old women presents for a routine health
  maintenance visit. She is monogamous with one
  partner. She has had 3 normal paps in the last 3
  years. She has never had an abnormal pap. What
  is the recommended interval for her pap?
• a) Yearly
• b) Every 2 years
• c) Every 3 years
• d) Every 5 years

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Cases (cont)

• 74 year old woman presents for routine follow-up
  for diabetes and osteoarthritis. She has had
  normal Pap smears every 2 years for the past 16
  years, with her last exam two years ago. When
  would you perform her next Pap smear?
• A) today
• B) in 1 year
• C) in 2 years
• D) I would not perform any additional paps

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Conclusions

• Screen for cervical cancer
• Remember that 50 of women diagnosed with
  cervical cancer had never been screened
• For interns, make sure an attending observes and
  gives you feedback.
• How to improve our rate of screening?
• Set up systems that make it easy to do a PAP
• Preplanned trays in each room
• Variable sized speculum in each room
• Cytology requisition slips easily available to
  nurses

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References

• Rollins Developments in Cervical and Ovarian
  Cancer Screening Implications for Current
  Practice. Annals of Int Med 2000 133 1021-1024.
• Saslow et al. American Cancer Society Guideline
  for Early Detection of Cervical Neoplasia and
  Cancer. CA Cancer J Clinic. 2002 52342-62.
• Solomon et al. The 2001 Bethesda System. JAMA.
  2002 287 2114-9.
• Wright et al. 2001 Consensus Guidelines for the
  Management of Women with Cervical Cytologic
  Abnormalities. JAMA. 2002 287 2120-9
• Goodman. Case 32-2003 A 37 year Old Woman with
  Atypical Squamous Cells on a Papanicolaou Smear.
  New Eng J Med. 2003 349 1555-64.
• Agar et al. HPV Testing in the Evaluation of the
  Minimally Abnormal Papanicolaou Smear. Am Fam
  Physician.1999 59
• Papillo et al. Evaluation of the ThinPrep Pa test
  in clinical practice. A seven-month, 16,314-case
  experience in northern Vermonth. Acta Ctyol.
  1998. 42 203-8.
• Linder et al. The ThinPrep Pap test. A review of
  clinical studies. Acta Cytol. 1997. 41 30-8.
• Obwegeser. Does liquid-based technology really
  improve detection of cervical neoplasia? A
  prospective, randomized trial comparing the
  ThinPrep Pap Test with the conventional Pap test,
  including follow-up of HSIL cases. Acta cytol.
  2001. 45 709-14.
• HPV Information for Clinicians CDC, November
  2006
• Brown et al. Cost Effectiveness of 3 Methods to
  Enhance the Sensitivity of Papanicolaou testing.
  JAMA. 1999. 281(4) 347-53.
• Bidus et al. Cost-Effectiveness Analysis of
  Liquid-Based Cytology and Human Papillomaviurs
  Testing in Cervical Cancer Screening. Obstet
  Gynecol, 2006 997-1005.
• Shiremen et al. Time Costs Associated with
  Cervical Cancer Screening. Int J of Tech Asses.
  in Healthcare. 2001 17(1) 146-152.
• Goldie SJ Kim JJ Wright TC. Cost-effectiveness
  of human papillomavirus DNA testing for cervical
  cancer screening in women aged 30 years or more.
  Obstet Gynecol 2004 Apr103(4)619-31.
• Bidus MA Maxwell GL Kulasingam S Rose GS
  Elkas JC Chernofsky M Myers ER.
  Cost-effectiveness analysis of liquid-based
  cytology and human papillomavirus testing in
  cervical cancer screening. Obstet Gynecol. 2006
  May107(5)997-1005.
• Ronco et al.
• Bos AB, van Ballegooijen M, Elske van den
  Akker-van Marle M, Hanselaar AG, van Oortmarssen
  GJ, Habbema JD. Endocervical status is not
  predictive of the incidence of cervical cancer in
  the years after negative smears. Am J Clin
  Pathol. 2001115851-855.

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Checklist for preceptors

• Appropriate comfort level for patient
• Insert speculum noting patient comfort
• Visualizes cervix
• If unable to visualize cervix, uses alternative
  method to attempt visualization
• Uses spatula before cytobrush
• Removes speculum with comfort