An overview of cervical cancer Ref. Williams

1. CERVICAL NEOPLASIA
AND CARCINOMA
Discussion:
報告者: 醫五 楊 憶
overview

2. CERVICAL NEOPLASIA
• Cervical cancer can be thought as a
preventable cancer.
• It is preceded by an identifiable precursor
lesion(cervical intraepithelial neoplasia,
CIN) that may(but not always) progress to
invasive cancer.

5. ETIOLOGY
• Cervical cancer and CIN are caused by HPV
• HPV
§ High risk : 16, 18, 31, 33, 35, 45, 52 and 58
§ Low risk : 6, 11 (genital warts)
• Produces proteins:
• E6 - inactivates p53
• E7 - inactivates pRb

6. ETIOLOGY
• The metaplastic cells within the TZ are the most
vulnerable to oncogenic change
• HPV infection is usually transient
• Persistent HR-HPV infection is necessary for
the development of cervical neoplasia.
• A minority of HPV infections become persistent,
but most young women (65%) with HPV16/18
infections lasting >6 months will develop SIL

8. CERVICAL NEOPLASIA
DIAGNOSIS
• In general, LGT preinvasive lesions are visible
only with aided inspection.
• Cervical cytology (Pap test)
• HPV testing
• All symptoms suspicious or cervical neoplasia
and grossly visible cervical lesions require
prompt biopsy.

9. PAP SMEAR/ TEST
• Conventional glass slides (Pap smear) and liquid-
based Pap tests are considered equally
acceptable for screening by all current guidelines.
• Specificity: 98%
• Sensitivity (CIN 2 or worse): 45-65%
→ Repetitive screening

10. PAP TEST
• Avoid menstruation
• Abstain from vaginal intercourse, douching, vaginal
tampon use, and intravaginal medicinal or
contraceptive creams for a minimum of 24-48h
before a test
• Treatment of cervicitis or vaginitis prior to Pap
testing is optimal
• Not deferred due to unexplained discharge or
unscheduled bleeding

11. CYTOLOGY WITH
HR HPV COTESTING
• Improved sensitivity for CIN 3 or cervical cancer
• Cytology(-) HPV(-) → repeat at 5y intervals
• Cytology(-) HPV(+) → repeat 12 m later
• Cytology (+) → guideline
• Colposcopy is recommended for persistently
positive HPV DNA test results

12. CYTOLOGY REPORTING
-THE BETHESDA SYSTEM
1.
2.
• Specimen Adequacy:
• Cellularity
• Presence of obscuring blood or
inflammation
• TZ components (not required for
adequacy; if lacking, repeat pap test in 3y)
• Unsatisfactory
• Repeat in 2-4m
• Treat atrophy or infection in advance
• Unsatisfactory again → colposcopy
• Unexplained vaginal discharge/ abnormal
bleeding/ abnormal physical findings
→ immediate evaluation

13. CYTOLOGY REPORTING
-THE BETHESDA SYSTEM
1.
2.

15. SCREENING GUIDELINES
• Initiation: Ideally age 21 in average risk women
• HIV → soon after diagnosis, even before age 21
• Interval:
• 21-29y → cytology alone at 3y intervals
• 30-65y → continue screening with cytology alone at 3y
intervals or begin cotesting at 5y intervals
• Women with HIV and other immune suppression
→ annual cytology screening
• 台灣健保給付：30歲以上每年一次

16. SCREENING GUIDELINES
• Discontinuation: >65y, average risk and adequate
screening
• Adequate screening:
• Three consecutive Pap(-) or two consecutive cotest(-)
(In the prior 10y, with the most recent within the past 5y)
• Average risk:
• Prior treatment for CIN 2, CIN 3,AIS, or cervical cancer
should continue routine screening for at least 20y
• Uncertain when HIV-positive women can discontinue

17. SCREENING GUIDELINES
• Post-hysterectomy:
• Total + no past history of high-grade CIN or cervical cancer → (X)
• Supra-cervical → (O) continue screening

18. EVALUATION
• Abnormal Pap test → visual inspection + bimanual
• 1st : Exclude the presence of invasive carcinoma
• 2nd : Determine grade and distribution
• Options for evaluation:
• Repeat cytology
• HPV testing
• Colposcopy w/ direct biopsy
• Endocervical assessment

19. SQUAMOUS CELL ABNORMALITY
• In general: If >ASC-US → colposcopy, exceptions:
• ASC-US
• if HR HPV(+), risk ≒ LSIL
• abnormal repeat result
• LSIL
• <25y
• HSIL

20. GLANDULAR CELL ABNORMALITY
• Squamous neoplasia is more frequently diagnosed than
glandular neoplasia upon evaluation of AGC cytology
• Elevated risk of endometrial and other reproductive
tract cancers and cancers at other sites (such as breast
and colon)
• Approximately half of the neoplasia diagnosed
subsequent to an AGC Pap is endometrial

22. CARCINOMA
• Squamous cell carcinoma/ Adenocarcinoma
• Highest risk of invasive cancer
• Invasive cancer O/X?
• Diagnostic excision procedure

23. COLPOSCOPY
• General assessment
• Cervical visualization
• SCJ visibility
• TZ classification
• Specific colposcopic findings
• Margin
• Color : Acetowhitening
• Vessels
• Iodine staining

24. BIOPSY
• Ectocervical
• Endocervical
• Colposcopy is inadequate, or colposcopy is adequate but no
lesion is identified
• Initial evaluation of ASC-H, HSIL,AGC, or AIS cytology test
results
• Surveillance 4-6m after excisional therapy if specimen
margins are positive for HSIL
• Surveillance after conization for AIS has been performed in
women wishing fertility preservation. Negative endocervical
curettage results add reassurance to this management

25. PREGNANCY
• Managed according to guidelines for the general
population
• Colposcopy and ectocervical biopsy are safe and
accurate during pregnancy
• Endocervical and endometrial sampling are not
performed during pregnancy to avoid amnionic
membrane rupture and infection
• Preinvasive neoplasia is not treated
→ reevaluate postpartum

26. CIN MANAGEMENT

28. CIN TREATMENT
• Ablation
• Cryosurgery
• CO2 laser
• Excision
• LEEP
• Cold-knife conization (CKC)
• Laser conization

29. CERVICAL CARCINOMA
• The etiology of cervical cancer is HPV (99.7% of cases)
• Squamous cell carcinoma (75%)- HPV16
• Adenocarcinoma (20-25%)- HPV18

30. CLINICAL EVALUATION
• Signs and symptoms of early cervical carcinoma are
variable and nonspecific (watery vaginal discharge,
intermittent spotting, postcoital bleeding…)
• Accurate diagnosis can be made by cytologic screening,
colposcopy w/ biopsy, or biopsy of a gross or palpable
lesion

31. CLINICAL EVALUATION
• Signs and symptoms of early cervical carcinoma are
variable and nonspecific (watery vaginal discharge,
intermittent spotting, postcoital bleeding…)
• Accurate diagnosis can be made by cytologic screening,
colposcopy w/ biopsy, or biopsy of a gross or palpable
lesion

32. STAGING- FIGO
• Cervical cancer is considered a clinically staged entity
• Allowable components of staging :
• Cold-knife conization (biopsy)
• Pelvic examination under anesthesia
• Cystoscopy
• Proctoscopy
• Chest radiograph → lung metastasis
• Intravenous pyelogram (or CT scan of this portion)
• Bullous edema is not sufficient for the diagnosis of bladder
involvement, and this involvement must be biopsy proven
• Lymph node metastasis does not change the clinical stage

33. Early
stage
Advanced
stage

35. RADIOLOGIC IMAGING
• MRI, CT, PET
• Although imaging does not affect assignment of stage,
imaging results can tailor treatment for an individual

36. LYMPH NODE DISSECTION
• May modify a patient’s primary treatment strategy based
on the level of nodal disease
• Dissection of the common iliac and paraaortic region
and resection of macroscopic lymph nodes
• Traditional laparotomy vs. minimally invasive surgery
→ MIS advantages + less radiation morbidity
• Aggressive surgical debulking
→ only 4-6% survival benefit

37. TREATMENT
• Generally
• Early-stage → Surgery (Hysterectomy or trachelectomy)
• Advanced-stage → Chemoradiation
(cisplatin weekly x5 + CCRT)

38. HYSTERECTOMY
• Type I : Simple hysterectomy
• Type II : Modified radical hysterectomy
• Type III : Radical hysterectomy

39. RADICAL TRACHELECTOMY
• Preserve fertility in selected young women with cervical
cancer
• Performed less often

40. TREATMENT
• Behavior
• Vaccines

41. SURVEILLANCE
• Following Radiotherapy
• Response → should regress within 3m after therapy
• 3m intervals for 2 yrs, 6m intervals until 5 yrs, then annually
• Pap teat annually for 20 yrs
• Vaginal dilator or vaginal intercourse 3 times/wk

42. SURVEILLANCE
• Following surgery
• 80% of recurrences are within the first 2 yrs
• Pelvic recurrences after radical hysterectomy, if diagnosed
early, can be treated with radiation therapy

43. SURVEILLANCE
• Hormone therapy
• Not contraindicated to treat menopausal symptoms
• Strongly considered for any premenopausal patient
undergoing radiation treatment for cervical cancer until the
average age of menopause

44. PROGNOSIS
• FIGO stage
• Lymph node involvement
• Lymph node metastasis
• Adenocarcinomas have worse overall survival rates at
every stage compared with squamous cell carcinoma

45. PREVENTION
• Behavior
• Screening
• Vaccines

47. REFERENCES
• Williams Gynecology, 3e.
• Obstetrics and Gynecology by Beckmann, 7e.
• Dewhurst’s Obstetrics and Gynecology, 9e.
• 國家衛生院 婦癌臨床治療指引(2011)
• Google 圖片