The ratings of the strength of recommendation (A-E), the quality of the evidence (I-III), and terminology used by the consensus conference (recommended, preferred, acceptable, unacceptable) are defined at the end of the Major Recommendations.
Note from the American Society for Colposcopy and Cervical Pathology (ASCCP): The management of low-grade cervical intraepithelial neoplasia (CIN) grade 1 has been modified significantly since 2001. Previously, management depended on whether colposcopy was satisfactory and treatment using ablative or excisional was acceptable for all women with CIN 1. In the new guidelines, cytological follow-up is the only recommended management option for women with CIN 1 who have low-grade referral cervical cytology, regardless of whether the colposcopic examination is satisfactory. Treatment is particularly discouraged in adolescents. The basic management of women in the general population with CIN 2,3 underwent only minor modifications, but options for the conservative management of adolescents with CIN 2,3 have been expanded. Moreover, management recommendations for women with biopsy-confirmed adenocarcinoma in situ are now included.
When human papillomavirus deoxyribonucleic acid (HPV DNA) testing is recommended, it applies only to testing for "high-risk" oncogenic HPV types using a validated assay.
Recommended Management of Women with Cervical Intraepithelial Neoplasia 1 (CIN 1)
CIN 1 preceded by atypical squamous cells of undetermined significance (ASC-US); atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion (HSIL) (ASC-H), or cytological low-grade squamous intraepithelial lesion (LSIL) cytology.
The recommended management of women with a histological diagnosis of CIN 1 preceded by an ASC-US, ASC-H, or LSIL cytology is follow-up with either HPV DNA testing every 12 months or repeat cervical cytology every 6 to 12 months. (BII) If the HPV DNA test is positive or if repeat cytology is reported as ASC-US or greater, colposcopy is recommended. If the HPV test is negative or 2 consecutive repeat cytology tests are "negative for intraepithelial lesion or malignancy," return to routine cytological screening is recommended. (AII)
If CIN 1 persists for at least two years, either continued follow-up or treatment is acceptable. (CII) If treatment is selected and the colposcopic examination is satisfactory, either excision or ablation is acceptable. (AI) A diagnostic excisional procedure is recommended if the colposcopic examination is unsatisfactory, the endocervical sampling contains CIN, or the patient has been previously treated. (AIII)
Treatment modality should be determined by the judgment of the clinician and should be guided by experience, resources, and clinical value for the specific patient. (A1) In patients with CIN 1 and an unsatisfactory colposcopic examination, ablative procedures are unacceptable. (EI) Podophyllin- or podophyllin-related products are unacceptable for use in the vagina or on the cervix. (EII) Hysterectomy as the primary and principal treatment for histological diagnosed CIN 1 is unacceptable. (EII)
CIN 1 Preceded by HSIL or AGC-NOS Cytology
Either a diagnostic excisional procedure or observation with colposcopy and cytology at 6 month intervals for 1 year is acceptable for women with a histological diagnosis of CIN 1 preceded by HSIL or atypical glandular cells–not otherwise specified (AGC-NOS) cytology, provided in the latter case that the colposcopic examination is satisfactory and endocervical sampling is negative. (BIII) In this circumstance it is also acceptable to review the cytological, histological, and colposcopic findings; if the review yields a revised interpretation, management should follow guidelines for the revised interpretation. (BII)
If observation with cytology and colposcopy is elected, a diagnostic excisional procedure is recommended for women with repeat HSIL or AGC-NOS cytological results at either the 6- or 12-month visit. (CIII) After 1 year of observation, women with 2 consecutive "negative for intraepithelial lesion or malignancy" results can return to routine cytological screening. A diagnostic excisional procedure is recommended for women with CIN 1 preceded by a HSIL or AGC-NOS cytology in whom the colposcopic examination is unsatisfactory, except in special populations (e.g., pregnant women). (BII)
CIN 1 in Special Populations
Adolescent Women
Follow-up with annual cytological assessment is recommended for adolescents with CIN 1. (AII) At the 12 month follow-up, only adolescents with HSIL or greater on the repeat cytology should be referred to colposcopy. At the 24 month follow-up, those with an ASC-US or greater result should be referred to colposcopy. (AII) Follow-up with HPV DNA testing is unacceptable. (EII)
Pregnant Women
The recommended management of pregnant women with a histological diagnosis of CIN 1 is follow-up without treatment. (BII) Treatment of pregnant women for CIN 1 is unacceptable. (EII)
Recommended Management of Women with CIN 2, 3
Initial Management
Both excision and ablation are acceptable treatment modalities for women with a histological diagnosis of CIN 2,3 and satisfactory colposcopy, except in special circumstances (see following text). (AI) A diagnostic excisional procedure is recommended for women with recurrent CIN 2,3. (AII) Ablation is unacceptable and a diagnostic excisional procedure is recommended for women with a histological diagnosis CIN 2,3 and unsatisfactory colposcopy (AII). Observation of CIN 2,3 with sequential cytology and colposcopy is unacceptable, except in special circumstances (see following text). (EII) Hysterectomy is unacceptable as primary therapy for CIN 2,3. (EII)
Follow-up after Treatment
Acceptable post-treatment management options for women with CIN 2,3 include HPV DNA testing at 6 to 12 months. (BII) Follow-up using either cytology alone or a combination of cytology and colposcopy at 6 month intervals is also acceptable. (BII) Colposcopy with endocervical sampling is recommended for women who are HPV DNA positive or have a repeat cytology result of ASC-US or greater. (BII) If the HPV DNA test is negative or if 2 consecutive repeat cytology tests are "negative for intraepithelial lesion or malignancy," routine screening for at least 20 years commencing at 12 months is recommended. (AI) Repeat treatment or hysterectomy based on a positive HPV DNA test is unacceptable. (EII)
If CIN 2,3 is identified at the margins of a diagnostic excisional procedure or in an endocervical sample obtained immediately after the procedure, reassessment using cytology with endocervical sampling at 4 to 6 months after treatment is preferred. (BII) Performing a repeat diagnostic excisional procedure is acceptable. (CIII) Hysterectomy is acceptable if a repeat diagnostic procedure is not feasible.
A repeat diagnostic excision or hysterectomy is acceptable for women with a histological diagnosis of recurrent or persistent CIN 2,3. (BII)
CIN 2,3 in Special Populations
Adolescent and Young Women
For adolescents and young women with a histological diagnosis of CIN 2,3 not otherwise specified, either treatment or observation for up to 24 months using both colposcopy and cytology at 6 month intervals is acceptable, provided colposcopy is satisfactory. (BIII)
When a histological diagnosis of CIN 2 is specified, observation is preferred but treatment is acceptable. When a histological diagnosis of CIN 3 is specified or when colposcopy is unsatisfactory, treatment is recommended. (BIII)
If the colposcopic appearance of the lesion worsens or if HSIL cytology or a high-grade colposcopic lesion persists for 1 year, repeat biopsy is recommended. (BIII) After 2 consecutive "negative for intraepithelial lesion or malignancy" results, adolescents and young women with normal colposcopy can return to routine cytological screening. (BII)
Treatment is recommended if CIN 3 is subsequently identified or if CIN 2,3 persists for 24 months. (BII)
Pregnant Women
In the absence of invasive disease or advanced pregnancy, additional colposcopic and cytological examinations are acceptable in pregnant women with a histological diagnosis of CIN 2,3 at intervals no more frequent than every 12 weeks. (BII) Repeat biopsy is recommended only if the appearance of the lesion worsens or if cytology suggests invasive cancer. (BII) Deferring reevaluation until at least 6 weeks postpartum is acceptable. (BII) A diagnostic excisional procedure is recommended only if invasion is suspected. (BII) Unless invasive cancer is identified, treatment is unacceptable. (EII) Reevaluation with cytology and colposcopy is recommended no sooner than 6 weeks postpartum. (CIII)
Recommended Management of Women with Adenocarcinoma in Situ (AIS)
Hysterectomy is preferred for women who have completed child-bearing and have a histological diagnosis of AIS on a specimen from a diagnostic excisional procedure. (CIII) Conservative management is acceptable if future fertility is desired. (AII) If conservative management is planned and the margins of the specimen are involved or endocervical sampling obtained at the time of excision contains CIN or AIS, reexcision to increase the likelihood of complete excision is preferred. Reevaluation at 6 months using a combination of cervical cytology, HPV DNA testing, and colposcopy with endocervical sampling is acceptable in this circumstance. Long-term follow-up is recommended for women who do not undergo hysterectomy. (CIII)
Definitions:
Rating the Recommendations
Strength of Recommendation*
- Good evidence for efficacy and substantial clinical benefit support recommendations for use.
- Moderate evidence for efficacy or only limited clinical benefit supports recommendation for use.
- Evidence for efficacy is insufficient to support a recommendation for or against use, but recommendations may be made on other grounds.
- Moderate evidence for lack of efficacy or for adverse outcome supports a recommendation against use.
- Good evidence for lack of efficacy or for adverse outcome supports a recommendation against use.
Quality of Evidence*
- Evidence from at least one randomized controlled trial
- Evidence from at least one clinical trial without randomization, from cohort or case-controlled analytic studies (preferably from more than one center), or from multiple time-series studies, or dramatic results from uncontrolled experiments
- Evidence from opinions of respected authorities based on clinical experience, descriptive studies, or reports of expert committees
Terminology**
Recommended: Good data to support use when only one option is available.
Preferred: Option is the best (or one of the best) when there are multiple other options.
Acceptable: One of multiple options when either there are data indicating that another approach is superior or when there are no data to favor any single option.
Unacceptable: Good data against use.
*Modified from Gross PA, Barrett TL, Dellinger EP, et al. Purpose of quality standards for infectious diseases. Infectious Diseases Society of America. Clin Infect Dis 1994;18:421 and Kish MA. Guide to development of practice guidelines. Clin Infect Dis 2001;32:8511.
**The assignment of these terms represents an opinion ratified by the Consensus Conference.
