Asccp 2013 somsak

1. Cervical cancer prevention
รศ. นพ. วีรศักดิ์ วงศ์ถิรพร
รศ. นพ. สมศักดิ์ ไหลเวชพิทยา
ผศ. นพ. สุธี สังขรัตน์
อ. นพ. บุญเลิศ วิริยะภาค
(สงวนสิทธิ์ในการทาสาเนาและเผยแพร่ทุกรูปแบบก่อนได้รับอนุญาต)
30 เมย 2556

2. Steps in HPV Induced
Cervical Cancer
HPV
infection
Persistent
HPV infection
Cellular
dysregulation
High grade
CIN
Invasive
cancer
Immunologic
factors
Co-carcinogens

3. HPV genes (E6,E7)in the Cell Cycle
E6gene product
Bindsp53
E7gene product
Binds pRb
Go G1 S G2 M Go
Growth
Signal
p53 and pRb
“ All clear signals “
Cell cycle progression
Apoptosis
Genetic
Repair
E6-E7
E6-E7
Minor DNA
damage
Major DNA
damage

4. : ~70% of cases can clear infection in 1yrs and
90% in 2 yrs.
: Most of persistent infection resulting in no
disease in their life but HPV DNA are +ve or
low level.
: ~30% progress to CIN 1, 10 – 20% CIN 2-3.
: Only 1% progress to cervical cancer.

5. Persistent
HPV
or
LSIL
Normal
Epithelial
Cell
HSIL
Inv. CA
HPV
1-2 yrs 3-20 yrs6-9 Months
Transient
HPV
Infected
Cells
HR-HPV DNA
Cytology
VIA (M)*
Colposcopy**
Age to
start
Age to
stop
interval
Natural history of Ca. Cx.2° Prevention of Ca. Cx.1° Prevention of Ca. Cx.
X

6. 2° Prevention of Ca. Cx.
Persistent
HPV
or
LSIL
Normal
Epithelial
Cell
HSIL
Inv. CA
HPV
1-2 yrs 3-20 yrs6-9 Months
HR-HPV DNA +ve
Cytology -ve
VIA (M) -ve
Colposcopy -ve
HR-HPV DNA +ve
Cytology ± ve
VIA (M) ±ve
Colposcopy ±ve
HR-HPV DNA +ve
Cytology +ve
VIA (M) +ve
Colposcopy +ve
Transient
HPV
Infected
Cells
All
tests
-ve

7. Cervical cancer prevention
(Cytology based)
• Screening programme
• Sampling and processing technique
• Reporting system
• Management of abnormal Pap smear

8. Cytology screening programme
• Age to initiate screening
• Frequency of screening
• Age to stopped screening

9. Potential Reduction in Cumulative Cervical Cancer Rate
with Difference Screening Frequencies
Frequencyof screening* PercentReduction in Cumulative rate**
1 yr 93 (30 smears)
2 yrs 93 (15 smears)
3 yrs 91 (10 smears)
5 yrs 84 ( 6 smears)
10 yrs 64 ( 3 smear)
IARC, , 1986
* Screeningall women age 35 to 64 whohave had atleast one previousnegativesmear.
**Reductionsassume 100% screeningsensitivity, screeningcoverageover 80% and effective
treatmentof everywomenin whom high-gradedysplasia is detected.

10. กรมการแพทย์ กระทรวงสาธารณสุขประเทศไทย
( เริ่มเมื่อ พ.ศ. 2511)
กลุ่มเป้าหมายอายุ 30*,35, 40, 45, 50, 55 และ 60 ปี
กลุ่มอื่นๆ ถ้ายืนยันต้องการตรวจ ก็บริการให้
ถ้าผลตรวจปกติ นัดครั้งต่อไปตามเกณฑ์อายุที่กาหนด
* พ.ศ.2553

11. Age group (yr) Frequency of screening
25 First invitation
25-49 Three yearly
50-64 Five yearly
65+ Only screen those who have not been
screenedsince age 50 or those who have had
recent abnormal tests
NHSCSP Publication No 20 April 2004
UK NHS 2011

12. Cervical cancer
50% of cases have not been screened,
60% of cases are inadequate screening,
10% have not been screened within 5
years before diagnosis.

13. American Cancer Society,
American Society for Colposcopy and Cervical Pathology
American Society for Clinical Pathology
ASCCP Copyright © 2012
Screening Guidelines for the Prevention
and Early Detection of Cervical Cancer

14. : Preventing all cervical cancer is unrealistic.
: No screening test has perfect sensitivity.
: There will always be a residual cancer risk
following any round of screening.
ASCCP Copyright© 2012

15. These guidelines were developed to
address cervical cancer screening in the
general populations, do not address
special, high-risk populations who may
need more intensive or alternative
screening.
ASCCP Copyright© 2012

16. 1) Who had a history of cervical cancer.
2) Who were exposed to DES in utero.
3) Who are immune-compromised (e.g.
HIV infection )
ASCCP Copyright© 2012

17. Population† ACS/ASCCP/ASCP§
< 21 years Women should not be screened
regardless of the age of sexual
initiation or other risk factors.
Screening Guidelines for the Prevention
and Early Detection of Cervical Cancer
ASCCP Copyright© 2012

18. : Cervical cancer is rare in adolescents and
young women.
: More rapidly progressive cervical cancers,
such as those occurring in women in their
teens and early twenties, may not be
preventable through feasible screening
strategies.
ASCCP Copyright© 2012

19. Adolescent cervical cancer prevention
programs should focus on universal HPV
vaccination, which is safe, highly efficacious,
and when used in adolescents before
becoming sexually active, highly effective and
cost-effective.
ASCCP Copyright© 2012

20. Population† ACS/ASCCP/ASCP§
21–29 years
( 3 tests )
Screening with cytology alone
every 3 years is recommended.
Based on good evidence showing similar
sensitivity and specificity of conventional
and liquid-based cytology for CIN grade
or more severe diagnoses (CIN2+).
ASCCP Copyright© 2012

21. The lifetime risk of cervical cancer associated
with screening interval. ( U.S.)
:No screening 31-33 per 1000 women
: Annually 3 per 1000 women
: 2 years 4 - 6 per 1000 women
: 3 years 5 - 8 per 1000 women
3 yrs. interval
ASCCP Copyright© 2012

22. The lifetime risk of death due to cervical ca.
associated with screening interval.
Annually 0.03 per 1000 women
2 years 0.05 per 1000 women
3 years 0.05 per 1000 women
3 yrs. interval
ASCCP Copyright© 2012

23. For women 21-29 years of age with 2 or
more consecutive negative cytology
results, there is insufficient evidence to
support a longer screening interval (i.e.
>3 years).
3 yrs. interval
ASCCP Copyright© 2012

24. Population† ACS/ASCCP/ASCP§
30 - 65
years
( 7 tests )
( 12 tests)
Screening with cytology and HPV
testing (“co-testing”) every 5 years
(preferred) or
cytology alone every 3 years
(acceptable) is recommended.
ASCCP Copyright© 2012

25. Population†
USP
STF ‡
ACS/ASCCP/ASCP§
Older than
65 years
Women with evidence of adequate
negative prior screening* and no history
of CIN2+ within the last 20 years should
not be screened.
Screening should not be resumed for
any reason, even if a woman reports
having a new sexual partner.
ASCCP Copyright© 2012

26. *Adequate negative prior screening is defined
as 3 consecutive negative cytology results or
2 consecutive negative cotests within the 10
years before ceasing screening, with the most
recent test occurring within the past 5 years.
4 3 2 1
55 56 57 58 59 60 61 62 63 64 65
3 2 1
cytology
age
co-test
66
ASCCP Copyright© 2012

27. Population†
USP
STF ‡
ACS/ASCCP/ASCP§
After
hysterectomy
Women of any age following a
hysterectomy with removal of the
cervix who have no history of CIN2+
should not be screened for vaginal
cancer. Evidence of adequate negative
prior screening is not required.
Screening should not be resumed for
any reason, including if a woman
reports having a new sexual partner.

28. Population†
USP
STF ‡
ACS/ASCCP/ASCP§
HPV
vaccinated Recommended screening practices
should not change on the basis of
HPV vaccination status.
ASCCP Copyright© 2012

29. Cervical cancer
50% of cases have not been screened,
60% of cases are inadequate screening,
10% have not been screened within 5
years before diagnosis.
Management of normal and
abnormal screening tests

30. Cervical cancer
50% of cases have not been screened,
60% of cases are inadequate screening,
10% have not been screened within 5
years before diagnosis.

32. V
C
E

33. Vaginal pool
ectoCervix & Endocervical
scraping

35. Inadequate sample

36. Good smear

39. Negative for Intraepithelial Lesion or Malignancy

40. Mild dysplasia
CIN1&HPV (LSIL)

41. Moderate dysplasia
CIN 2 (HSIL)

42. Severe dysplasia / CIS
HSIL

43. Invasive adenocarcinoma
Invasive squamouscell ca.

44. Siriraj Liquid-based Preparation

45. Conventional Pap
Siriraj liquid-based

46. การรายงานผลการตรวจ Pap smear
• Papanicolaou Classification ( Class 1 - 5 )
• WHO Classification ( 1973 )
• Bethesda System ( 1993 )
• Bethesda System (2001)

47. Pap WHO
Class 1 Normal
Class 2 Inflammation, Atypia
Class 3 Dysplasia (CIN)
Mild dysplasia , CIN 1
Moderatedysplasia, CIN 2
Severedysplasia, CIN 3
Class 4 Carcinoma in situ (CIS)
Class 5 Invasive SCC
AIS
Adenocarcinoma
Malignantcells of other tumour types
Bethesda 2001
Negative for intraepithelial lesion or malignancy
Infection, inflammation, reactive changes
SquamousIntraepithelial Lesion (SIL)
ASC-US , ASC-H
Low grade (LSIL): HPV and/or CIN 1
High grade (HSIL): moderate and severe
dysplasia, CIN 2, CIN 3, CIS and
with features suspicious for invasion
Invasive Squamouscell carcinoma
Glandular cell abnormality
AGC , favourneoplastic , AIS
Adenocarcinoma
Other malignantneoplasms

48. Pap WHO
Class 1
Negative for malignancy
Class 2
Inflammation, Atypia
Bethesda 2001
Negative for intraepithelial
lesion or malignancy
Infection, inflammation,
reactive changes

49. Pap WHO
Class 3
Dysplasia (CIN)
Mild dysplasia , CIN 1
Moderate dysplasia, CIN 2
Severe dysplasia, CIN 3
Class 4 Carcinoma in situ (CIS)
Class 5
Invasive SCC
AIS
Adenocarcinoma
Malignant cells of other tumor
types
Bethesda 2001
Squamous Intraepithelial Lesion (SIL)
ASC-US , ASC-H
Low grade(LSIL): HPV and/orCIN 1
High grade (HSIL):moderate and
severe dysplasia, CIN 2, CIN 3, CIS ,
with features suspicious for invasion
Invasive Squamous cell carcinoma
Glandular cell abnormality
AGC , favour neoplastic , AIS
Adenocarcinoma
Othermalignant neoplasms

50. Bethesda system 2001
Negative for Intraepithelial Lesion or Malignancy (NILM)
Organisms:
- Trichomonas vaginalis
- Fungal organisms morphologically consistent with Candida spp.
- Shift in flora suggestive of bacterial vaginosis
- Bacteria morphologically consistent with Actinomyces spp.
- Cellular changes consistent with Herpes simplex virus
< Pap Class 1> http://bethesda2001.cancer.gov/terminology.html

51. Neg. for intraepithelial lesion or malignancy

52. Trichomonas vaginalis
Neg. for intraepithelial lesion or malignancy

53. Fungal organisms morphologically consistent with Candida spp.
Neg. for intraepithelial lesion or malignancy
Candida spp

54. Clue cell
Neg. for intraepithelial lesion or malignancy
Shift in flora suggestive of bacterial vaginosis

55. Actinomyces spp.
Neg. for intraepithelial lesion or malignancy
Bacteria morphologically consistent with Actinomyces spp.

56. Neg. for intraepithelial lesion or malignancy
Cellular changes consistent with Herpes simplex virus

57. Bethesda system 2001
Other Non Neoplastic findings < Pap Class 2>
- Reactive cellular changes associated with
• inflammation ( includes typical repair)
• radiation
• Intrauterine device (IUD)
- Atrophy
- Glandular cells status post hyterectomy
Other
• Endometrial cells (in woman ≥ 40 years of age)
http://bethesda2001.cancer.gov/terminology.html

58. Neg. for intraepithelial lesion or malignancy
Reactive cellular changes associated with inflammation
Inflammatorycellular change

59. Bethesda system 2001
Epithelial cell abnormality
Squamous cell
• Atypical squamous cells
– of undetermined significance (ASC-US)
– cannot exclude HSIL (ASC-H)
• Low grade squamous intraepithelail lesion (LSIL) <Pap class 3>
encompassing: HPV/mild dysplasia /CIN 1
• High grade squamous intraepithelail lesion (HSIL)
encompassing: moderate and severe dysplasia, CIS/CIN 2, 3
• With features suspicious for invasion < Pap class 4 >
• Invasive Squamous cell carcinoma < Pap class 5 >
http://bethesda2001.cancer.gov/terminology.html

60. ASC (Atypical squamous cell)
ASC-US (Atypical Sq. Cells of Undetermined Significance)
:- Cytologic changes that are suggestive of a SIL, but
lack criteria for a definitive interpretation.
ASC-H (Atypical Sq. Cells; Cannot Exclude HSIL)
:- Cytologic changes that are suggestive of HSIL, but lack
criteria for definitive interpretation.

61. ASC-US
(Atypical squamous
cells of undetermined
significant)

62. ASC-H
(Atypical squamous cells cannot exclude HSIL)

63. LSIL (HPV)

64. HSIL

65. HSIL

66. SCC

67. Bethesda system 2001
Epithelial cell abnormality
Glandular cell
• Atypical < Pap class 3 >
– endocervical cells
– endometrial cells
– glandular cells (NOS or specify in comment)
• Atypical, (favor neoplastic) < Pap class 4 >
- endocervical cells, favor neoplastic
– glandular cells, favor neoplastic
• Endocervical adenocarcinoma in situ < Pap class 4 >
• Adenocarcinoma < Pap class 5 >
» EC, EM, Extrauterine, Not Otherwise Specify (NOS)
http://bethesda2001.cancer.gov/terminology.html

68. AGC endocervical cell

69. AGC endometrial cell

70. Adenocarcinoma

71. Adenocarcinoma Extrauterine origin

72. Bethesda system 2001
Other malignant neoplasms: (specify)
- Small cell carcinoma
- Neuroendocrine carcinoma
- Carcinosarcoma
- Sarcoma
- Lymphoma
- etc.
http://bethesda2001.cancer.gov/terminology.html

73. Cx Histo.(%)
Siriraj LBC (25,510)
Neg. CIN 1 CIN2-3 SCC Adeno
NILM (1,012) 96.34 0.49 0.99 0.49 1.68
ASC-US (13) 53.85 38.46 7.69 0.00 0.00
ASC-H (33) 12.12 27.27 39.39 12.12 9.09
LSIL (41) 14.63 78.05 7.32 0.00 0.00
HSIL (124) 8.06 18.55 61.29 8.06 4.04
SCC (26) 0.00 0.00 7.69 76.92 15.38
Adeno ca. (18) 19.05 4.76 19.05 9.52 47.62
Predective values of Siriraj LBC ( yr, 2006)
CIN2+ (60.6%)
CIN2+ (73.39%)
LaiwejpithayaS, et al. Eur J Obstat Gynecol.2009 ; 147 : 201-205
CIN2+ (76.19%
CIN1+ (46.15%)
CIN1+ (87.87%)
CIN1+ (85.37%)
CIN1+ (91.94%)
CIN2+ (100%

74. It is important to note that
• Cytologic LSIL is not equivalent to CIN 1
• Cytologic HSIL is not equivalent to CIN 2,3
Am J Obstet Gynecol 2007; Oct: 340-355.

75. Abnormal Pap Smear
ASC-US, ASC-H
LSIL, HSIL
Invasive sq. cell ca.
AGC
AGC, favor neoplastic
AIS
Adenocacinoma

76. Non-neoplastic process
• Inflammatory cellular changes
• Reactive or Reparative changes
Neoplastic process
(ASC-US)
• LSIL 20-30 %
• HSIL 15-20 %
• Inv. CA < 1 %
ASC (Atypical squamous cell)
ASC-US, ASC-H
• Atrophic change
• Radiation effect

77. Management
for Atypical squamous cells
 Cytology
 High risk HPV DNA testing
 Colposcopy

78. AGC (Atypical glandular cell)
Atypical
• endocervical cells
• endometrial cells
• glandular cells (NOS, not otherwise specified)
Atypical, favor neoplastic
• endocervical cells, favor neoplastic
• glandular cells, favor neoplastic

79. Managemaet
for Atypical glandular cells
 Cytology
 High risk HPV DNA testing
 Colposcopy
 Endocervical curettage (ECC)
 F/C, Endometrial sampling
 Diagnostic conization

80. ASC-US
on cytology
Repeat cytology
@ 1 yr
Acceptable
Negative ≥ ASC
Routine screening
with cytology
in 3 yrs. interval
Colposcopy
HR-HPV DNA
Preferred
+ HPV - HPV
Repeat cotesting
@ 3 yrs. interval
Modified from ASCCP Copyright 2013

81. ?
Co-testing ( Cytology + HR HPV test )
Cyto. -ve /HPV -ve
Cyto. +ve /HPV +ve
Cyto. -ve / HPV +ve
Routine screening with Co-testing
in 5 yrs. interval
Colposcopy
Cyto.LSIL+/HPV -ve
Option 1
Option 2
Cyto. ASCUS / HPV -ve
Repeat with Co-testing
@ 3 yrs.interval
Modified from ASCCP Copyright 2013

82. Co-testing
HPV +ve
or
Cyto. ≥ ASC
Cyto. -ve / HPV +ve
Option 1
Repeat Co-testing @ 1 yr. Acceptable
cyto. –ve / HPV -ve
Repeat co-testing
@ 3 yrs. Colposcopy
Modified from ASCCP Copyright 2013

83. Co-testing HPV +ve / Cyto. -ve
Repeat Co-testing @ 1 yr.
Colposcopy
Option 2
HPV 16/18 +ve HPV 16/18 -ve
HPV -ve / cyto. -ve
HPV DNA Typing
Acceptable
HPV +ve
or
Cyto. ≥ ASC
Repeat co-testing
@ 3 yrs.
Modified from ASCCP Copyright 2013

84. Thank you
for your attention
References
• www.asccp.org
• www.bethesda2001.cancer.gov
• www.ajog.org
• Laiwejpithaya S,et al. Eur J Obstet Gynecol Reprod
Biol 2009 :Dec : 201-205.
• สงวนสิทธิ์ในการทาสาเนาและเผยแพร่ทุกรูปแบบก่อนได้รับอนุญาต
รศ.นพ. สมศักดิ์ ไหลเวชพิทยา
30 เมษายน 2556

85. Persistent
HPV
or
LSIL
Normal
Epithelial
Cell
HSIL
Inv. CA
HPV
1-2 yrs 3-20 yrs6-9 Months
Transient
HPV
Infected
Cells
2° Prevention of Ca. Cx.
HR-HPV DNA
Cytology
VIA (M)
Colposcopy
HR-HPV DNA
Cytology
Cytology
VIA (M)
Cytology
Colposcopy
CytologyHR-HPV DNA VIA (M)
Colposcopy

86. Visual Inspection with Acetic â
( under Magnification)
Visual Inspection

87. Siriraj cervicoscope
Magnification ~ 7x
Focal length ~ 30 cm.
Magnification ~ 7x
Focal length ~ 30 cm.

90. Colposcopy

91. Colposcopy

92. Cervical Biopsy

93. LEEP
Rx
2 weeks
after Rx
6 weeks
after Rx

94. Condyloma acuminata