Review the latest recommendations with

Emma L. Grabinski, MD, FACOG

Dr Grabinski, a generalist OBGYN, is System Chief of OBGYN & Perinatology at Swedish Medical Center, and a clinical adjunct Professor at UW in Seattle WA

Learning Objectives: Upon completion of this activity, participant should be better able to

• Discuss cervical screening and management of immunocompromised people
• Describe cervical screening and management post treatment for malignancy
• Counsel patients in unusual screening and management situations, applying knowledge of hrHPV biology

SUMMARY:

The new ASCCP management guidelines provide recommendations on the management of cervical cancer screening abnormalities. But sometimes, we have to deal with unusual or more challenging situations. The key point to remember with the following, less typical clinical scenarios is that successful outcomes hinge on not only following best practices but individualizing care.  

CONTENTS:

• Case 1: Immunocompromise
• Case 2: Limited Prior Screening
• Case 3: Persistent hrHPV
• Case 4: Testing after History of Malignancy or CIN 2/3
• Case 5: Post Coital Bleeding

Case 1: Immunocompromise

17 year old recently became sexually active, wants to discuss contraception options.  She has a history of Crohn’s disease that is well controlled with a biologic. You suggest cervical cancer screening, but the patient is surprised – she thought Pap screening didn’t start until age 21

• Immunocompromise, due to HIV and non-HIV related causes
  • Increases the risk for hrHPV-related cervical dysplasia and malignancy
  • Requires more intense screening, surveillance, and treatment

Who to Screen

• HIV infection
• Solid organ transplant recipients
• Hematopoietic stem cell transplant recipients
• IBD on immunosuppressants
• SLE – regardless of treatment
• RA on immunosuppressants

How to screen

• Starting age
  • 21 years or within 1 year of sex if immunosuppressed <21 years
• Screening strategy
  • <30 years: Cytology preferred
  • ≥30 years: Co-testing preferred | Cytology acceptable
• Repeat every 1 to 3 years
  • Recent data of HIV infected people suggests that after a period of intense screening, the interval can be lengthened
• When to stop
  • Continue past age 65 | Discontinue screening based on shared discussion regarding quality and duration of life rather than age

How to Manage

• Neg Pap/hrHPV+ or ASCUS with unknown or hrHPV-
  • Repeat in 6 to 12 months
• ASCUS or hrHPV+
  • Colposcopy
• ASCUS or higher-grade lesion and hrHPV+
  • Colposcopy
  • Risk of immediate CIN 3+ is always >4% in the immunocompromised population

Case 2: Limited prior screening  

32 year old new patient presents for pelvic pain discussion.  They deny previous abnormal Pap results, but you do not have records.  They are unsure when they last had a Pap.  Current screening results show ASCUS and hrHPV+

• Risk of immediate CIN 3+ is >4% (based on cytology results)
  • Recommendation is for colposcopy
• Rarely screened patients are at higher risk
  • We are not able to be certain whether hrHPV+ result represents a new infection or persistence
• Race, ethnicity, and socioeconomic considerations all contribute to lower screening rates for cervical cancer
  • Discrepancies in access to follow up results in higher rates of cervical cancer
• Opportunistic screening is important in the following clinical settings
  • Limited prior screening
  • Reliability for follow up is reduced (often related to social factors, including limited access to healthcare resources)

Case 3: Persistent hrHPV

52 year old established patient, presents for colposcopy due to a report that is negative for intra-epithelial lesions and malignancy (NILM) and hrHPV+.  This is their 4^th consecutive colposcopy for the same result.  Current and previous colposcopy does not show CIN 2/3+.  She is frustrated and wonder if they need to continue doing colposcopy

• HPV persistence is essential for development of cervical cancer
• Current ASCCP/ACOG guidelines recommend repeat co-testing in 1 year, with colposcopy if ASCUS+/hrHPV+
• The Swedescreen Study showed that HPV persistence (with normal colposcopy) over 6 years resulted in either high rates of CIN2+ or clearance
  • No cases of invasive cancer were identified in this 6 year interval
• However, continued annual testing may result in non-attendance for follow up
  • Loss to follow-up may potentially result in failure to identify people with CIN 2+
• Evidence of HPV persistence after treatment for CIN shows that there is significant clearance of HPV within 24 months after LEEP or conization

Counseling Options for This Patient

• Continued screening
  • ASCCP approved interval: Annually until either clearance of HPV or development of CIN 2+
  • May extend screening interval that is acceptable to patient | Should be demonstrated that patient will be reliable with follow up
• Treatment
  • HPV clearance has been demonstrated after LEEP or conization: May be reasonable option for patients wishing to avoid long term follow up
  • Hysterectomy is not recommended for treatment of hrHPV | However, in people with no desire for future fertility and who may have other indications for hysterectomy, this approach may be a reasonable option

Case 4: Testing after Malignancy or CIN 2/3

A 47 year old patient presents 5 years after radical hysterectomy for Stage 1(b)i squamous cell carcinoma of the cervix. They have ‘graduated’ from follow up with gyn oncology and are here for a preventive exam. They wonder whether they should still have pap smears.

Hysterectomy for CIN 2/3

• Primary vaginal cancer extremely rare – however is significantly higher in this population.
  • 0.4-0.6/100,000
• hrHPV+ prevalence of the vagina is similar whether hysterectomy has, or has not been done
  • Hysterectomy for CIN2/3 will NOT result in clearance of hrHPV
  • Accuracy of vaginal cytology and hrHPV testing has not been determined for diagnosing VAIN2/3
    • PPV ranges from 0-14%
• Per ASCCP, patients should be followed with cytology every 3 years for a minimum of 25 years after hysterectomy
  • Depends on life expectancy and degree of co-morbid conditions
  • Discuss whether patient would have further intervention for VAIN 2/3 or malignancy to determine whether to screen or when to stop screening
    • Risk after hysterectomy for CIN 2/3 similar to risk of vaginal cancer after treatment for invasive cervical cancer
    • Consider not performing after counseling based on low risk of developing malignancy
• Colposcopy recommended for the following
  • Any high grade cytology (ASC-H, HGSIL, AGC)
  • Low grade cytology (ASCUS, LGSIL) with HPV 16/18 positive
  • 2x annual cytology with low grade cytology (ASCUS/LGSIL ) +/- hrHPV

Endometrial Cancer

• Most recurrences happen at the vaginal cuff
  • Cytology has been shown to be abnormal in 25% of recurrence
  • However, most recurrence is detected based on clinical symptoms
  • Abnormal cytology may also represent radiation changes
• Cytology has not been shown to add clinical benefit and is not recommended

Ovarian Cancer

• Cytology not recommended

Cervical Cancer

• 75% of recurrence occurs in first 3 years
  • NCCN recommends follow up every 3 to 6 months in first 2 years, and then every 6 months for the next 3 years
  • Most will present with symptoms (46 to 95%)
  • Physical exam detects asymptomatic recurrence in 29 to 75% of people
• Abnormal cytology
  • Rarely the only abnormal finding
  • Does not significantly increase detection rates | Only up to 17% of cases will be based on cytology alone
  • The rate of abnormal cytology in people with prior radiation and no recurrence can be up to 36% | Most are ASCUS
• SGO ‘Choosing Wisely Campaign’ recommends
  • Vaginal cytology (if used) no more frequently than annually
  • No colposcopy if cytology shows less than high grade changes

Vulvar/Vaginal Cancer

• Usually HPV mediated
• Cytology
  • Not recommended for follow-up to detect recurrence | Reserved cytology for HPV related cervical premalignant disease
  • Should have annual comprehensive vulvar exam to detect recurrence

Case 5: Post Coital Bleeding (PCB)

44 year old presents with a 6 month history of abnormal bleeding.  On evaluation, the bleeding is occurring mainly after penetrative intercourse.  She reports her last Pap was 3 years ago and was normal

• Cervical cancer screening guidelines (ASCCP, ACS, USPSTF) are for ASYMPTOMATIC patients only
  • Patients with abnormal bleeding do not fit into these algorithms, and visualization of the cervix with sampling of the cervix with cytology and/or biopsy may be appropriate
  • Send these results for ‘diagnostic’ NOT ‘screening’ interpretation
• Prevalence of cervical cancer is 3 to 5.5% in people with PCB
  • PCB is the presenting complaint in 11% of people with cervical cancer

Cervical cancer is very unlikely in the following situations and therefore colposcopy may not be clinically appropriate if pelvic exam benign

• <21 yo
• Regardless of age:
  • Negative cytology in the past 12 months
  • Negative co-testing in the past 3 years

Consider colposcopy if the following applies, regardless of screening results

• Visible cervical lesion
• Persistent PCB
• PCB with persistent minor cytological anomalies
• Immunocompromised
• at risk for inadequate cytological screening
• Other causes to consider when assessing a patient with PCB
  • Polyps | Infection | Atrophy | Other genital tract malignancy (vaginal or endometrial cancer) | Sexual abuse

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REFERENCES:

2019 ASCCP Risk-Based Management Consensus Guidelines for Abnormal Cervical Cancer Screening Tests and Cancer Precursors

Guidelines for Cervical Cancer Screening in Immunosuppressed Women Without HIV Infection (Moscicki et al. J Low Genit Tract Dis, 2019)

Risk Estimates Supporting the 2019 ASCCP Risk-Based Management Consensus Guidelines (Egemen et al. J Low Genit Tract Dis, 2019)

Patterns of persistent HPV infection after treatment for cervical intraepithelial neoplasia (CIN): A systematic review (Hoffman et al. Int J Cancer, 2017)

Human papillomavirus genotype prevalence in invasive vaginal cancer from a registry-based population (Sinno et al. Obstet Gynecol, 2014)

A Common Clinical Dilemma: Management of Abnormal Vaginal Cytology and Human Papillomavirus Test Results (Khan et al. Gynecol Oncol, 2016)

An update on post-treatment surveillance and diagnosis of recurrence in women with gynecologic malignancies: Society of Gynecologic Oncology (SGO) recommendations (Salani et al. Gynecol Oncol, 2017)

Postcoital bleeding: a review on etiology, diagnosis, and management (Tarney and Han. Obstet Gynecol Int, 2014)

Commercial Support

This educational activity is supported by Hologic

Faculty Disclosures

Dr. Grabinski reports that she has no relevant financial relationships to disclose

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