HPV Testing is essential in the triage of ASC-US and/or LSIL cytology. The test helps to clearify the situation after treatment of high-grade CIN and to resolve uncertainties after diagnostic and or consecutive treatment. 2016 up to date information is give by the presentation. Primary HPV testing or co-testin

1. Uses of HPV Testing in Triage of
Cervical Cytology
Dr Dirk Grothuesmann
Cervical Cytology (Up to date, 2016)
http://dg-maternalhealth.de/

2. Uses of HPV Testing alongside Cytology
• Triage of ASC-US and/or LSIL cytology
• Test of cure after treatment of high-grade CIN
• Resolution of uncertainties
• Primary HPV testing or co-testing

3. Uses of HPV Testing alongside Cytology

4. Principles of HPV Testing
• HPV is more sensitive than cytology for CIN2+
• Early detection of CIN2 is not an end in itself because almost half of
CIN2 lesions would resolve naturally without treatment
• Detection of CIN2+ depends on sensitivity of colposcopy
• HPV specificity is considerably lower than cytology
• Most HPV-positive lesions represent transient infection
• Persistent HPV-positive lesions are at risk for progression
• HPV is not 100% sensitive for CIN2+, CIN3+ or cancer

5. Progression of CIN Categories
HIGH-GRADE SQUAMOUS LESION
(HSIL) — HSIL refers to moderate to severe
changes in the cells of the cervix. The risk
that these abnormalities reflect precancerous
changes is as high as 20.8%, and the risk of
cervical cancer is as high as 1.4%

6. HPV triage of ASC-US or LSIL cytology
ASC-US atypical cells of undetermined significance
LSIL Low-grade squamous intraepithelial lesion
• In ASC-US Hybrid Capture 2 (HC2) to be significantly more sensitive
than repeat cytology in detecting CIN2+
• no more sensitive in detecting CIN3
• 40% of CIN2 lesions had regressed
• In LSIL HPV triage was not recommended for LSIL, most of which was
hrHPV+

7. Summary of HPV ASC-US/LSIL triage
• Allows about half of women with ASC-US to be returned to routine
screening due to HPV negativity
• Detects more CIN2+ than cytological surveillance
• Detects more CIN3+ in meta-analyses but not at all centres
(depending on the sensitivity of cytology)

8. In view of frequent regression of CIN2,
immediate treatment may not be mandatory in
young women and requires histology and
cytology review

9. Test of cure after treatment of CIN
• Women may be at increased risk of cancer for up to 20 years after
treatment of CIN3 (Strander et al. 2007)
• A four-fold increased risk of cancer has been reported after treatment
of any grade of CIN and three negative cytology tests (Rebolj et al.
2012)
• Among 15 studies with 2-year follow up, the risk of recurrent CIN
varied between 4% and 18% (average 8%) in 15 studies (Flannelly et
al. 2001)

10. Risk of CIN3+ within 10 years
Post-treatment disease in women treated for high-
grade cervical disease
• 29% of HPV-positive women (i.e. 6%)
• 13% of women with ASC-US+ cytology (i.e. 3%)
• 22.5% of women positive for either or both (i.e. 7%)
• 2.1% of HPV-negative women (i.e. 2%)
• 2.8% of cytology-negative women (i.e. 2%)
• 1.4% of double-negative women (i.e. 1%)
Kocken et al., Gynecologic Oncology, vol. 125, no. 2, pp. 500–507, 2012

11. Co-testing after Treatment
• Risk of CIN2+ recurrence after negative co-testing at 24 months or
three negative cytology tests was similar to the risk of CIN2+ in the
general population
• As a result of this study the authors recommended co-testing at 6 and
24 months - or three cytology tests at 6, 12 and 24 months if HPV
testing is not available.

12. HPV testing to resolve uncertainty (e.g.
persistent CIN1)
• HPV testing was positive in one-third to half of women
• CIN2+ rates were higher in HPV+ women (8% vs. 0.7%)
• HPV testing in this setting highlights the problem of managing HPV-
positive women who do not have CIN2+

13. ASC-US Management using HPV Triage
HPV Test with Hybrid-capture using High Risk Probe
ASC-US Pap Test
High Risk HPV positive High Risk HPV negative
Perform Coloposcopy Repeat Pap in 12 month

15. http://dg-maternalhealth.de/
Dr Dirk Grothuesmann Consultancy