Results of Sentinel Sites Study Dr Karin Denton. HPV testing as a triage for women with low grade...

Results of Sentinel Sites Study

Dr Karin Denton

• HPV testing as a triage for women with low grade cytological abnormalities: results from the sentinel sites studies.

Kelly R, Patnick J, Kitchener HC, Moss SM

Br J Cancer. 2011 Sep 27;105(7):983-8.

Results

• Study took place between 1 Jan 2008 and 1 April 2009

• Data collected until September 2009

• Analysis conducted independently at Cancer Screening Evaluation Unit, Institute of Cancer Research

• Over 90% of women attended colposcopy

North Bristol NHS Trust/Avon Cervical screening programme

HPV positive rates by age group and initial cytology result

Borderline Mild Total

Age Grp No of women

HPV + n (%)

No of women

HPV + n (%)

No of women

HPV + n (%)

25-34 31212144(68.7)

22031964(89.2)

53244108(77.2)

35-49 27831165(41.9)

1129869

(77.0)3912

2034(52.0)

50-64 603187

(31.0)212

141(66.5)

815328

(40.2)

Total 65073496(53.7)

35442974 (83.9)

100516470(64.4)


SSS Results from different centresHPV positive rate by site and initial

cytology 1

Site Borderline Mild Total

n HPV +ve(%)

n HPV +ve(%)

n HPV +ve (%)

A

B

C

D

E

F

1263

643

2557

789

663

592

866 (68.6)

224 (34.8)

1111 (43.4)

455 (57.7)

406 (61.2)

434 (73.3)

404

523

1507

420

557

133

370 (91.6)

384 (73.4)

1232 (81.8)

372 (88.6)

500 (89.8)

116 (87.2)

1667

1116

4064

1209

1220

7255

1236 (74.1)

608 (52.1)

2343 (57.7)

827 (68.4)

906 (74.3)

550 (75.9)


SSS Results from different centresHPV positive rate by site and initial cytology

2Site Borderline Mild Total

n HPV +ve(%)

n HPV +ve(%)

n HPV +ve (%)

Centre C(Thinprep® LBC)

1188 543 (47.7) 798 669 (83.8) 1986 1236 (61.0)

Centre C(BD SurepathTM LBC)

426 216 (50.7) 241 204 (84.6) 667 420 (63.0)

Total(Thinprep® LBC)

3903 2270 (58.2) 2179 1911 (87.7) 6082 4181 (68.7)

Total(BD SurepathTM LBC)

1661 874 (52.6) 897 704 (78.5) 2558 1578 (61.7)


Sentinel Site StudyResults at colposcopy

CIN 1 CIN2 CIN3+

n (%) n (%) n (%)

BL 25-34

35-49

50-64

394 (20.4)

173 (16.3)

27 (15.8)

193 (10.0)

88 (8.3)

4 (2.3)

142* (7.4)

65 (6.1)

5 (2.9)

Total 594 (18.8) 285 (9.0) 212 (6.7)

Mild 25-34

35-49

50-64

468 (26.7)

236 (29.6)

31 (23.8)

217 (12.4)

87 (10.9)

8 (6.2)

111 (6.3)

30 (3.8)

3 (2.3)

Total 735 (27.5) 312 (11.7) 144 (5.4)

Total 1239 (22.8) 597 (10.2) 356 (6.1)


*Includes 3 invasive cancers

Sentinel Site StudyPPV of colposcopy by site 1

Site Borderline Mild

No attending colposcopy

PPVCIN2+

PPVCIN3+

No attending colposcopy

PPVCIN2+

PPVCIN3+

A

B

C

D

E

F

803

178

978

430

355

417

21.5

11.2

11.6

16.5

9.3

20.9

7.8

6.2

5.0

7.4

2.5

11.5

350

317

1104

354

440

112

25.4

9.1

15.9

21.8

10.9

30.0

7.1

3.5

4.8

7.6

2.5

15.2


Sentinel Sites StudyRate of disease at 1, 2 3 and >3 years after negative colposcopy in

956 women with long term follow-up

Time since negative colposcopy

Abnormal cytology CIN1 CIN2 CIN3

No. % No. % No. %. No. %

1 year

2 years

3 years

>3 years

10

19

25

30

1.0

2.0

2.6

3.1

18

33

38

49

1.9

3.5

4.0

5.1

6

16

19

23

0.6

1.7

2.0

2.4

10

19

23

28

1.0

2.0

2.4

2.9


Test of Cure• Preliminary data only in un-triaged women

• 3203 women had test of cure

• Failed test of cure by 18.3%– 6.2% by abnormal cytology– 12.1% by HPV +ve with normal cytology

• Increased ‘failure’ rates with lower CIN grade

• Persistent CIN2+ in 7%– 3% in HPV +ve– 13% in cytology +ve


Bristol experience

Bristol Outcome Lletz histology for mild and borderline HPV positive smears with CIN 2/3 on

PB(%)

Histol

Smear\Nil HPV/

inflam

CIN1 CIN2 CIN3 Micro

B’line

HPV

3 13 10 35 38 1

Mild

HPV

8 8 12 29 41 2

National outcomes

• 90% attendance

• Half had PB (47% negative histology)

• 2.4% had LLETZ ( 28% neg histology)

• 1/3 of identified CIN1 were not treated

• Apparent overall cytological progression was 3.4% at 12 months

Role for HPV testingTest of cure

Smear + hpv test 6 months

after treatment

Cytology negativeHPV negative3 year recall

Cytology negative and HPV positive – recall colp (12%)

Cytology positiveRecall colp (6%)

Biopsy/treat

Colp satisfactory3 year recall Colp unsatisfactory

Colp abnormalBiopsy and retreat

(4.8%)

Management outcome in women referred to Colposcopy following

HPV Test of Cure (TOC)Mohini Vachhani, Mary Brett*,

Anne Vaughton, Vikki Finch, John Murdoch

Colposopy Clinic and *Cellular Pathology Dept,

Southmead Hospital

Presented 22/06/2011

(Also, poster at BSCCP meeting 31.3-1.4/2011)

Results

• No of samples with HPV TOC test = 2369

• HPV negative = 2017 (85%) routine recall

• HPV positive = 352 (15% - National rate 18%) colposcopy

• Referred to Southmead = 141

• Referred to St Michael’s = 211

Outcome

• TZ seen; NAD –> Cytology follow up in Community (n = 66)

• TZ seen; abnormality seen (n = 22):

2 LLETZ (CIN 1, CIN2)

16 biopsy (3 CIN1, 13 neg)

4 rpt cytology (all negative)

Outcome

• Colposcopy was unsatisfactory in 30% of cases (i.e.TZ not seen): n = 38

• 6 had further LLETZ (all negative)

• 13 had Bx (1 CIN 1, 12 neg)

Outcome

• Total no with repeat LLETZ = 8 cases

• 7 had involved margins in index LLETZ

• 2/8 with satisfactory colp and abnormality seen (Histo: CIN1, CIN2)

• 6/8 with unsatisfactory colp (Histo: all negative)

Conclusion

• Women with positive TOC are at minimal risk of residual CIN (6/126 =4.8%)

• 5/126 (4%) = CIN1

• 1/126 (0.8%) = CIN2

• Nationally PPV for CIN2 or worse = 2.9% and for CIN3 or worse = 0.4%

Other studies

H Kitchener et al. BJOG 2008, 15(8): 1001-1007

• Of cyto neg/HPV pos referrals to colp, 9/75 had CIN (at 6, 12 or 24 months follow up post-LLETZ; 4 CIN1, 4 CIN2, 1 CIN3)

• = 12% treatment failure rate.

(Compared with Southmead data: 6/126 had residual CIN = 4.8%)

Changes to KC61?

Don’t panic, no change to data collection or categories

Longer term impact on KC61 data

• BC rate will fall (due to loss of 2nd and 3rd bc)

• Mild rate will also fall depending on previous policy

• Will be visible effect from year 1

• High grade rate will also fall slightly because women will be referred on a prior low grade result

• PPV should remain unaffected

Caution

• You must decide on a diagnosis and stick to it regardless of HPV result

• Do not use BC?HG in order to get an HPV test

• Follow the management protocol

ABC3

• ? Launch date

• Will abolish BC?HG

KEY TO CODES & ABBREVIATIONS

Action codes• A routine recall• Rm early repeat in 'm' months• S suspend from recall

PROVISIONAL Result codes• Ø * ?glandular neoplasia (non cervical) • G * ?glandular neoplasia (non cervical) (HPV tested)• 1 inadequate • 2 negative (not HPV tested)• N negative (HPV tested)• 3 low grade dyskaryosis (not HPV tested)• M low grade dyskaryosis (HPV tested)• 4 high grade dyskaryosis (severe)• 5 high grade dyskaryosis ?invasive squamous carcinoma• 6 ?glandular neoplasia of endocervical type• 7 high grade dyskaryosis (moderate)• 8 borderline change in squamous cells (not HPV tested)• B borderline change in squamous cells (HPV tested)• 9 borderline change in endocervical cells• E borderline change in endocervical cells (HPV tested)

• * non-cervical neoplasia treated as negative for CSP management

•

• Infection codes

• Ø (zero) HPV negative

• 9 (nine) HPV positive

• U HPV result inadequate/unreliable

•

• Miscellaneous

• NTDD Next Test Due Date

• BLUE indicates codes used on NHAIS in format

• Cytology result – HPV infection code – Action code

• RED indicates manual action required to reset NTDD

Questions?

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