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.

• 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
Age Grp
25-34
35-49
50-64
Total
Borderline
No of women
3121
2783
603
6507
HPV + n
(%)
No of women
2144
(68.7)
1165
(41.9)
187
(31.0)
3496
(53.7)
2203
1129
212
3544
Mild
HPV + n
(%)
No of women
1964
(89.2)
869
(77.0)
141
(66.5)
2974
(83.9)
5324
3912
815
10051
Total
HPV + n
(%)
4108
(77.2)
2034
(52.0)
328
(40.2)
6470
(64.4)
North Bristol NHS Trust/Avon Cervical screening programme

C
D
E
A
B
F
Site
HPV positive rate by site and initial cytology 1
Borderline n HPV +ve
(%)
1263
643
2557
789
663
592
866 (68.6)
224 (34.8)
1111 (43.4)
455 (57.7)
406 (61.2)
434 (73.3) n
Mild
HPV +ve
(%)
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 n
Total
HPV +ve
(%)
1236 (74.1)
608 (52.1)
2343 (57.7)
827 (68.4)
906 (74.3)
550 (75.9)
North Bristol NHS Trust/Avon Cervical screening programme

Site
Results from different centres
HPV positive rate by site and initial cytology 2
Borderline n HPV +ve
(%)
Mild n HPV +ve
(%) n
Total
HPV +ve
(%)
1188 543 (47.7) 798 669 (83.8) 1986 1236 (61.0)
Centre C
(Thinprep® LBC)
Centre C
(BD Surepath TM LBC)
426 216 (50.7) 241 204 (84.6) 667 420 (63.0)
Total
(Thinprep® LBC)
Total
(BD Surepath TM LBC)
3903 2270 (58.2) 2179 1911 (87.7) 6082 4181 (68.7)
1661 874 (52.6) 897 704 (78.5) 2558 1578 (61.7)
North Bristol NHS Trust/Avon Cervical screening programme

Results at colposcopy
BL
Mild
25-34
35-49
50-64
Total
25-34
35-49
50-64
Total
Total
*Includes 3 invasive cancers
CIN 1 n (%)
394 (20.4)
173 (16.3)
27 (15.8)
594 (18.8)
468 (26.7)
236 (29.6)
31 (23.8)
735 (27.5)
1239 (22.8)
North Bristol NHS Trust/Avon Cervical screening programme
CIN2 n (%)
193 (10.0)
88 (8.3)
4 (2.3)
285 (9.0)
217 (12.4)
87 (10.9)
8 (6.2)
312 (11.7)
597 (10.2)
CIN3+ n (%)
142* (7.4)
65 (6.1)
5 (2.9)
212 (6.7)
111 (6.3)
30 (3.8)
3 (2.3)
144 (5.4)
356 (6.1)

PPV of colposcopy by site 1
D
E
F
A
B
C
Site Borderline
No attending colposcopy
803
PPV
CIN2+
21.5
178 11.2
978
430
355
417
11.6
16.5
9.3
20.9
PPV
CIN3+
7.8
6.2
5.0
7.4
2.5
11.5
No attending colposcopy
350
Mild
PPV
CIN2+
25.4
317 9.1
1104
354
440
112
15.9
21.8
10.9
30.0
PPV
CIN3+
7.1
3.5
4.8
7.6
2.5
15.2
North Bristol NHS Trust/Avon Cervical screening programme

Rate of disease at 1, 2 3 and >3 years after negative colposcopy in
956 women with long term follow-up
Time since negative colposcopy
1 year
2 years
3 years
>3 years
Abnormal cytology
No.
%
10
19
25
30
1.0
2.0
2.6
3.1
No.
CIN1
%
18
33
38
49
1.9
3.5
4.0
5.1
No.
CIN2
%.
6
16
19
23
0.6
1.7
2.0
2.4
No.
CIN3
%
10
19
23
28
1.0
2.0
2.4
2.9
North Bristol NHS Trust/Avon Cervical screening programme

• 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
North Bristol NHS Trust/Avon Cervical screening programme

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

• 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

Cytology negative
HPV negative
3 year recall
Colp satisfactory
3 year recall
Smear + hpv test
6 months after treatment
Cytology negative and HPV positive
– recall colp (12%)
Colp unsatisfactory
Cytology positive
Recall colp (6%)
Biopsy/treat
Colp abnormal
Biopsy and retreat
(4.8%)

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)

• 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

• 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)

• 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)

• 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)

• 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%

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%)

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

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

• 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

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