Type 3 TZ (previously ‘unsatisfactory’) colposcopy following LBC prediction of Negative,LSIL or HSIL

GUIDELINE UPDATES - This guideline was last updated 01/07/2022

Evidence

Systematic reviews were conducted to answer the following questions:

For women with a positive oncogenic HPV (any type) test result, a LBC report of negative or LSIL, and Type 3 TZ (or unsatisfactory in previous terminology) colposcopy, what is the safety and effectiveness of 12-month follow-up testing with a HPV test alone, compared with co-testing (HPV and LBC)?
For women with positive oncogenic HPV (any type) test result, a cytology prediction of pHSIL/HSIL, and Type 3 TZ (or unsatisfactory in previous terminology) colposcopy, what is the safety and effectiveness of conservative management, compared with diagnostic excision of the TZ?

Type 3 TZ (previously termed ‘unsatisfactory’) colposcopy following LBC reported negative or prediction of LSIL

No randomised or pseudorandomised controlled trials were identified that compared testing strategies and reported cancer outcomes in women with a positive HPV test result, cytology reported negative or LSIL, and Type 3 TZ (unsatisfactory) colposcopy. The search strategies and inclusion and exclusion criteria used are described in detail in the Technical report.

In the absence of any direct evidence from the systematic review, a general review of the literature on the management of women with negative or pLSIL/LSIL cytology and a type 3 TZ colposcopy was undertaken to inform consensus-based recommendations.

No longitudinal studies were found that followed women with an initial cytology prediction of pLSIL/LSIL and Type 3 TZ (unsatisfactory) colposcopy. Three retrospective cross-sectional cohort studies[1][2][3] reported outcomes for women with pLSIL/LSIL initial cytology and an unsatisfactory colposcopy:

In a cohort of 427 women with ASC-US or LSIL cytology who underwent colposcopy (with endocervical curettage) and the entire squamocolumnar junction was not visible, CIN2+ lesions of the endocervical canal were diagnosed in 18 women (4.2%):[1] eight of these women either had not undergone cervical biopsy or had less than CIN2 disease on cervical biopsy. These also included two women with invasive cancer of the endocervical canal (0.5%), both of whom had a cervical biopsy report of CIN2+.CIN2+ was diagnosed in the endocervical canal in three of 256 women (1.2%) with a normal but unsatisfactory colposcopy, and 15 of 171 women (8.8%) with an abnormal and unsatisfactory colposcopy. The degree to which the findings of this study can be generalised to women in the renewed NCSP is limited, because neither HPV status nor the selection criteria for endocervical curettage was specifically reported.
In a cohort of 118 women with ASC-US or LSIL cytology who underwent colposcopy (with endocervical curettage) and either the entire squamocolumnar junction was not visible or a visible lesion not seen in its entirety, CIN2+ was diagnosed on cervical biopsy in 18 women (15.3%).[2] Of these women, six had endocervical as well as ectocervical disease. No additional cases were detected on endocervical curettage. The degree to which the findings of this study can be generalised to women in the renewed NCSP is limited, because neither HPV status nor the selection criteria for endocervical curettage was reported.
In a cohort of women with normal, ASCUS or LSIL cytology who underwent cone biopsy after an unsatisfactory colposcopy (entire squamocolumnar junction not visible or visible lesion not seen in its entirety) and CIN1 was detected on colposcopically guided biopsy, histologically confirmed CIN2+ was diagnosed in one woman (4.3%).[3] The degree to which the findings of this study can be generalised to women in the renewed NCSP is limited, because HPV status was not reported and 25% of the women were HIV-positive.

A summary of the literature considered can be found in the Technical report.

Overall, this body of evidence suggests that diagnostic excision of the TZ may detect additional clinically significant cervical lesions in women with cytology reported as LSIL and Type 3 TZ (unsatisfactory) colposcopy. In this situation, pre-renewal NCSP guidelines recommended repeating cytology in 12 months. In the renewed NCSP, it is appropriate to apply the same follow-up interval for the repeat HPV test (with reflex LBC if positive for any oncogenic HPV type).

Type 3 TZ (previously termed ‘unsatisfactory’) colposcopy following LBC prediction of HSIL

No randomised or pseudorandomised controlled trials were identified that compared conservative management with diagnostic excision of the transformation zone and reported cancer outcomes in women with a positive HPV test result, cytological prediction of HSIL, and Type 3 TZ (unsatisfactory) colposcopy. The search strategies and inclusion and exclusion criteria used are described in detail in the Technical report.

In the absence of any direct evidence from the systematic review, a general review of the literature on the management of women with HSIL cytology and Type 3 TZ (unsatisfactory) colposcopy was undertaken to inform consensus-based recommendations.

No longitudinal studies were found that followed women with an initial cytology prediction of pHSIL/HSIL and Type 3 TZ (unsatisfactory) colposcopy, with or without cytopathology review. Two retrospective cross-sectional cohort studies[4][5] reported outcomes for women with an initial prediction of pHSIL/HSIL and unsatisfactory colposcopy:

In a cohort of 78 women with a cytology prediction of HSIL and unsatisfactory colposcopy (entire TZ including squamocolumnar junction not visible) who underwent LEEP, CIN2+ was histologically confirmed in 43 women (55.1%).[4] Of these, one woman (1.3%) had invasive cervical cancer. CIN2+ disease (including the one case of cervical cancer) was found on LEEP in 35 (74.5%) of 47 women with HSIL cytology on review. The degree to which the findings of these studies can be generalised to women in the renewed NCSP is limited, because HPV status was not reported, and review cytology findings could not be compared with initial referral cytology findings or colposcopically directed biopsy findings for individual women. It was not possible to assess how many extra cases of CIN2+ were detected on LEEP.
In a cohort of 65 women with a cytology report of HSIL who underwent cone biopsy after colposcopy detected no visible lesions and was unsatisfactory (entire TZ not visible), CIN2+ was diagnosed in 25 women (38.5%) and invasive cervical cancer was diagnosed in three women (4.6%).[5] The degree to which the findings of these studies can be generalised to women in the renewed NCSP is limited, because neither HPV status nor the results of cytopathology review (if performed) was reported.

In both of these studies[4][5] a significant number of women were diagnosed with CIN2+ on excisional biopsy. This finding underpins an approach involving excision of the TZ when the referral cytology is HSIL after cytopathology review and the TZ cannot be fully visualised (Type 3 TZ), irrespective of a HPV test result.

A summary of the literature considered can be found in the Technical report.

Recommendations

Flowchart 8.4. Colposcopy Type 3 TZ after LBC prediction of Negative, pLSIL or LSIL

Flowchart 8.5. Colposcopy Type 3 TZ after LBC prediction of possible HSIL

Flowchart 8.6. Colposcopy Type 3 TZ after LBC prediction of HSIL

Flowchart 8.7. Colposcopy Type 3 TZ and no high grade histology: follow-up or treatment for some women

Consensus-based recommendation

REC8.9: Repeat HPV test after Type 3 TZ colposcopy and referral LBC negative or pLSIL/LSIL
For women who have a positive oncogenic HPV (any type) test result with a LBC report of negative or pLSIL/LSIL, and colposcopy is reported as Type 3 TZ,† the HPV test should be repeated in 12 months:

If oncogenic HPV is not detected at 12 months, the HPV test should be repeated 12 months later.
If oncogenic HPV is not detected again at the second repeat HPV test, the woman should be advised to return to routine 5-yearly screening.
If the woman has a positive oncogenic HPV (any type) test result at 12 months, she should be referred directly for colposcopic assessment, with the LBC report available to inform the assessment.