Updates in Pap Screening Part II: High Grade Lesions
/Here’s the RoshReview Question of the Week:
A 45-year-old woman presents to your office for follow-up. She has a history of postpartum tubal ligation. She had a colposcopy for high-grade squamous intraepithelial neoplasia. The procedure was performed at the office and revealed one white lesion after acetic acid application. Biopsy results reveal cervical intraepithelial neoplasia grade 1. The borders of this lesion were not entirely identified. Which of the following is the best next step in management?
We’re back this week with Part II on Pap smears! Let’s cover high grade lesions.
First, the easy part: any ASC-H result merits colposcopy, regardless of HPV status! The down-the-line management will vary by age.
In patients aged 21-24, ASC-H and HSIL get treated the same - colposcopy.
In patients 25 and older, ASC-H goes to colposcopy, but HSIL can proceed immediately to excision, or perform colposcopy first prior to excision.
Why is there an option to go straight to excision?
The overall 5 year CIN2+ risk for HSIL above age 25 is 77%, and for CIN3+ its 49%. Given those high risks, it is acceptable to proceed directly to excision without colposcopy.
Most women with HSIL will have HPV+ testing.
But even with negative HPV results, an HSIL test carries a 5-year risk of CIN3 of 25% and an invasive cancer risk of 7%. Thus, it’s still acceptable to proceed straight to excision in this scenario.
One way to think about this is the number needed to treat, which is super impressive. For HSIL HPV+, the NNT is 1.7 – that is, 1.7 excisional procedures for every CIN3+ treated – a very low rate of overtreatment!
For HSIL HPV-, the NNT is still very low at 2.8.
So we do a colpo and get biopsies… now what?
Your biopsy result will be a histology result – so CIN1, CIN2, CIN3, AIS, or invasive cancer. Let’s review the non-invasive management strategies for post-colposcopic biopsy.
CIN1 - this depends on the preceding Pap cytology, and the patient’s age:
HSIL cytology: many strategies are acceptable:
Observation, which entails colposcopy and cytology in patients under 25, or HPV-based testing with colposcopy in patients 25 and older, at one year.
An excisional procedure (not recommended in patients under 25)
Or a pathology review to determine if there is a discrepancy in the previous interpretation of cytology or histology.
With observation being most typical in younger patients:
Colposcopy and cytology/HPV testing should occur again in one year.
If these are negative, age specific retesting should happen again in an additional year, followed by HPV-based testing every 3 years for at least 25 years.
If there’s any abnormality, then manage that using the ASCCP guideline for the specific abnormality; though specifically, if HSIL again, excision is recommended.
Unless the patient is still under age 25, then observation can be continued for up to 2 years prior to recommendation for excision.
ASC-H cytology: observation is the most typical strategy:
Perform cytology if under 25, or HPV-based testing if > 25, in one year.
If negative, HPV-based testing can resume in 3 years from that.
If abnormal - you manage according to the ASCCP guideline.
Specifically, if progresses to HSIL – excision is recommended if over age 25.
If persistent ASC-H, can repeat again in 1 year, but excision is recommended if over age 25 and ASC-H persists for 2 years.
For those under age 25, HSIL or ASC-H should persist for two years before excision is recommended.
Lower grade cytology (ASC-US or LSIL):
Repeat co-testing at 12 months and 24 months.
If normal, then can have repeat testing in 3 years before resuming normal age-appropriate intervals.
If there is an abnormality in this 2 year window, then management should be performed according to cytology – though if there’s progression to HSIL, colposcopy and/or excision is recommended using the same guidelines as we stated for ASC-H.
CIN 2 or 3 on colposcopic biopsy - this will warrant an excisional procedure, typically.
For CIN2, observation is considered acceptable in patients under 25, or those over 25 if there are concerns about future pregnancy that, for the patient, outweigh their concerns about cervical cancer.
If that’s the case, colposcopy and HPV-based testing should occur at 6 and 12 months.
If two consecutive evaluations have less than ASC-H cytology and less than CIN2 histology, then testing can space to annually for 3 total years.
If the tests are abnormal, q6 month testing can continue for up to 2 years.
If CIN3 develops at any point, or the abnormalities persist for more than 2 years, excision becomes recommended.
For CIN3, observation is not advised – these should proceed to excision.
If you proceed with excision, the management is based on your excisional margins:
If margins are negative, then cotesting at 12 and 24 months is subsequently recommended, with repeat colposcopy needed for any abnormal result.
If margins are positive, then you have three choices:
Repeat cytology with endocervical curettage q4-6 months.
Repeat excision, if feasible.
Hysterectomy.
Notably, hysterectomy should only be considered if repeat excision is not feasible, or if high grade abnormalities are persistent after attempted repeat excision.
Adenocarcinoma In Situ (AIS)
If AIS is identified, excision is needed to rule out invasive cancer.
If margins are positive, reexcision is recommended to try to achieve negative margins.
If margins are negative, hysterectomy is generally preferred after the excision.
The excision is mandatory! You can’t proceed straight to hysterectomy – because if invasive cervical cancer is advanced enough, then hysterectomy may not be the recommended treatment.
If margins are negative, and the patient desires fertility, then reevaluation with HPV-based testing every 6 months for 3 years, then annually for two years, is acceptable.
Hysterectomy is recommended following childbearing, though!
Other Uncommon Pap Results
Unsatisfactory Cytology
Super frustrating! Your Pap didn’t have enough to evaluate!
Recommendations:
Follow your HPV result if you got it!
If HPV positive (especially 16/18), colposcopy is warranted.
If HPV is negative in someone 25 years or older, or if no HPV result, or unknown HPV result, then repeat the Pap in 2-4 months.
If the Pap is again unsatisfactory, colposcopy is recommended – good idea to take a look and figure out what you’re missing if two in a row are not satisfactory.
Negative for Intraepithelial Lesion, but Absent transformation zone or endocervical cells
This is also usually an insufficient Pap that didn’t sample that transformation area from glandular to squamous cell. This is the area where most HPV-associated disease is located, so effectively this is an insufficient Pap.
If Age 21-24, routine screening can continue.
If age 25+, HPV screening can triage:
If negative, routine screening can continue.
If unknown, repeat cytology in 3 years is acceptable, or get HPV testing (preferred).
If positive, then you follow the HPV-positive management guideline – which as a reminder for 16/18 is colposcopy, and for other types of HPV in this case would be to repeat the HPV-based test in one year.
Atypical Glandular Cells (AGC) and Atypical Endometrial Cells (AEC)
For these pathologies, a number of tests are recommended:
If atypical glandular cells or other subcategories,
Colposcopy with endocervical sampling is recommended.
Endometrial sampling should also be performed if the patient is 35 or older, or under 35 with risk factors such as AUB, chronic anovulation, or obesity.
If atypical endometrial cells
Endometrial and endocervical sampling are recommended, and colposcopy can also be performed –
and generally colposcopy should be performed, as if the other samplings are negative, colposcopy would then be warranted at that point.
Management would then proceed on the basis of these findings.
If no CIN2+, AIS, or cancer, then cotesting is recommended at 1 and 2 years, and can be spaced to every 3 years after that if remains negative.
If CIN2+ is identified, or if the initial cytology was concerning for neoplasia, then excisional procedure is typically recommended.