Uses of HPV Testing in Triage of Cervical

Cytology

Dr Dirk GrothuesmannCervical Cytology (Up to date, 2016)

http://dg-maternalhealth.de/

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

Uses of HPV Testing alongside Cytology

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

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%

HPV triage of ASC-US or LSIL cytology

ASC-US atypical cells of undetermined significanceLSIL 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+

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)

In view of frequent regression of CIN2, immediate treatment may not be mandatory in

young women and requires histology and cytology review

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)

Risk of CIN3+ within 10 yearsPost-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

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.

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+

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

http://dg-maternalhealth.de/

Dr Dirk Grothuesmann Consultancy