Associate Professor, Department of Obstetrics and Gynecology, Warren Alpert Medical School of Brown University, Women and Infants Hospital, Providence, RI

Dr. Allen reports she is a Nexplanon trainer for Merck, and has served as a consultant for Bayer and Pharmanest.

SYNOPSIS: In this study, routine endocervical curettage (ECC) among women age 30 and older detected CIN 2 or worse in 14.4% of cases with higher likelihood of detection among women with high-grade squamous intraepithelial lesion, ASC-H, positive HPV 16 infection, or high grade colposcopic impression. The additional yield of ECC over lesion-directed ectocervical biopsies decreased with each additional biopsy.

SOURCE: Liu AH, Walker J, Gage JC, et al. Diagnosis of cervical precancers by endocervical curettage at colposcopy of women with abnormal cervical cytology. Obstet Gynecol 2017; Nov 3. doi: 10.1097/AOG.0000000000002330. [Epub ahead of print].

This is a secondary analysis of the Biopsy Study, a cross-sectional study from the University of Oklahoma Health Science Center that evaluated the incremental benefit of multiple biopsies at colposcopy. Women were excluded from the study if they had previous treatment of cervical dysplasia, prior chemotherapy or radiation for cervical neoplasia, pregnancy, or known HIV infection. According to study protocol, up to four cervical biopsies were taken of acetowhite lesions. When less than four biopsies were taken, an additional non-directed biopsy was taken of a normal-appearing area on the transformation zone of the cervix. Women age 30 years or older were supposed to routinely receive endocervical curettage (ECC) and women younger than 30 years of age received ECC for the following: discrepancy between colposcopic findings and high-grade squamous intraepithelial lesion (HSIL) referral cytology, unsatisfactory examination, or atypical glandular cells (AGC) or adenocarcinoma in situ (AIS) cytology. A sharp Kevorkian curette was used to assess the endocervix, except in women with severe cervical stenosis, in whom a Cytobrush was permitted. Biopsy results were categorized as low-grade squamous intraepithelial lesion-LSIL (CIN [cervical intraepithelial neoplasia] 1 or less, p16 negative-CIN 2) or high-grade intraepithelial lesion-HSIL (p16 positive-CIN 2, CIN 3, cancer). The authors evaluated the yield of ECC in identifying CIN 2 or worse by itself and the additional yield of ECC in identifying CIN 2 or worse not otherwise found on biopsies of ectocervical lesions.

Of 204 women aged 30 years and older, 181 (89%) received an ECC. Among women younger than 30 years of age, 100 of 477 (21%) underwent an ECC. The ECC found CIN 2 or worse among 26 of the 181 women age 30 and older (14.4%). The yield of ECC in detecting CIN 2 or worse increased with age, from 10.1% among women 20 to 29 years of age to 25% among women 60 to 69 years of age. Yield was higher in women with ASC-H (atypical squamous cells, cannot rule out high grade) or HSIL or worse (includes AGS, AIS, squamous cell carcinoma) cervical cytology compared to women with ASCUS (atypical squamous cells of undetermined significance) or LSIL (low-grade squamous intraepithelial lesion) cytology (27.1% vs. 7.3%; P < 0.05). Yield also was higher in women positive for HPV 16 infection (24.4% vs. 11.5%; P < 0.05) or a high-grade colposcopic impression (26.8% vs. 8.0%; P < 0.05). The authors stratified women based on indications for ECC according to the current U.S. management guidelines for cervical cancer screening and management¹: for ASCUS or LSIL cytology, ECC is preferred when no lesions are found or exam is unsatisfactory, and it is acceptable when exam is satisfactory with visible colposcopic lesions; for ASC-H or HSIL, ECC is preferred for all nonpregnant women. Among women with ASCUS or LSIL, ECC found CIN 2 or worse in 4.3% of normal exams, 13% of unsatisfactory exams, and 1.9% of satisfactory exams with positive findings on the ectocervix. Among women with ASC-H or HSIL, ECC found CIN 2 or worse in 26% of cases. The additional yield of ECC for detecting precancers otherwise missed by ectocervical biopsies was 14.4% when no lesion-directed ectocervical biopsies were taken but decreased to 7.7%, 5.0%, 4.4%, and 3.9% when one, two, three, and four lesion-directed ectocervical biopsies were performed, respectively.

COMMENTARY

The study authors previously showed that increasing the number of ectocervical biopsies increased precancer detection during colposcopy.² The Biopsy Study showed a 25% increase in detection between the first and second lesion-directed biopsy and a 10% increase between the second and third lesion-directed biopsy. Although it is acknowledged that ECC is useful in older women in whom the transformation zone is receding into the endocervix as a result of hormonal changes, the question of whether to add ECC to colposcopy procedures routinely has been debated. Current American Society for Colposcopy and Cervical Pathology (ASCCP) guidelines prefer ECC be performed for any high-grade cytology and in women with ASCUS or LSIL cytology whose exams are unsatisfactory or in whom no lesions are found.¹ The current study seems to support these recommendations. The authors also believed that HPV 16 also indicated the need for ECC, especially in older women. In current clinical practice, however, the subtype of high-risk HPV is not always known at the time of colposcopy. The lack of selection bias as to who received ECC among women age 30 years and older is a major strength of this study. However, there are some limitations to this study, including smaller numbers of older women and low prevalence of HPV 18 infection, which limited analysis in some strata.

The ASCCP recently released consensus guidelines that outline recommendations for colposcopy standards across the United States where a wide range of provider types perform colposcopy.³ To date, colposcopic practice has been based on how one was trained, and there were no national guidelines specifically outlining pre-colposcopy evaluation, terminology, documentation, or the number of biopsies recommended. The ASCCP convened an expert committee and performed systematic analyses of the evidence to generate the recommendations. For example, the ASCCP recommended the minimum criteria for reporting findings at colposcopic examination include: squamo-columnar junction visibility (full visualized/not fully visualized), acetowhitening (yes/no), lesion(s) present (acetowhite or other) (yes/no), and colposcopic impression (normal/benign, low grade, high grade, cancer). Comprehensive documentation would add the following: cervix visibility (fully visualized/not fully visualized), lesion visualized (fully visualized/not fully visualized), location of lesion(s), size of lesion(s), vascular changes, and other features of lesion(s) (color, contour, borders, Lugol’s uptake, etc.). The executive summary of the recommendations are listed below.³

1. Adapting colposcopy practice to previous risk and colposcopy impression

Recommendation: Colposcopy practice may be modified based on the risk level (which can be viewed as the probability of finding precancer/cancer at the time of the procedure), based on reason for referral and colposcopy impression.

2. Number and type of biopsies taken at colposcopy

Recommendation: Multiple biopsies targeting all areas with acetowhitening, metaplasia, or higher abnormalities are recommended. Usually, at least two and up to four targeted biopsies from distinct acetowhite lesions should be taken.

3. Biopsy practice in women with low risk of precancer

Recommendation: Nontargeted biopsies are not recommended for women referred to colposcopy at the lowest end of risk, i.e., those with less than high-grade squamous intraepithelial lesion cytology, no evidence for HPV 16/18, and a completely normal colposcopic impression (i.e., no acetowhitening, metaplasia, or other visible abnormality).

4. Biopsy practice in women with very high risk of precancer

Recommendation: In nonpregnant women 25 years and older with very high risk of precancer (at least two of the following: high-grade squamous intraepithelial lesion cytology, HPV 16 and/or HPV 18 positive, high-grade colposcopy impression) either immediate excisional treatment without biopsy confirmation, or colposcopy with multiple targeted biopsies is acceptable. Endocervical sampling should be conducted according to the 2012 ASCCP Management Guidelines. If biopsies are taken and do not show precancer, management according to the 2012 ASCCP Management Guidelines is recommended.

These guidelines will help with colposcopy training, ensuring universal practice standards and quality improvement activities.

REFERENCES

1. Massad LS, Einstein MH, Huh WK, et al. 2012 updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors. 2012 ASCCP Consensus Guidelines Conference. J Low Genit Tract Dis 2013;17(5 Suppl 1):S1-S27.
2. Wentzensen N, Walker JL, Gold MA, et al. Multiple biopsies and detection of cervical cancer precursors at colposcopy. J Clin Oncol 2015;33:83-89.
3. Wentzensen N, Massad LS, Mayeaux EJ, et al. Evidence-based consensus recommendations for colposcopy practice for cervical cancer prevention in the United States. J Low Genit Tract Dis 2017;21:216-222.