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Literature review current through: Sep 2016. | This topic last updated: Jul 11, 2016.
INTRODUCTION — Cervical intraepithelial neoplasia (CIN) is a premalignant condition of the uterine cervix . The ectocervix (surface of the cervix that is visualized on vaginal speculum examination) is covered in squamous epithelium, and the endocervix, including the cervical canal, is covered with glandular epithelium. CIN refers to squamous abnormalities. Glandular cervical neoplasia includes adenocarcinoma in situ and adenocarcinoma. (See "Cervical cytology: Evaluation of atypical and malignant glandular cells" and "Cervical adenocarcinoma in situ" and "Invasive cervical adenocarcinoma".)
Screening tests for cervical cancer include cervical cytology and testing for oncogenic subtypes of human papillomavirus (table 1). Follow-up of abnormalities in screening tests with colposcopy and cervical biopsy may result in a diagnosis of CIN, glandular neoplasia, or cervical cancer .
CIN may be low grade (CIN 1) or high grade (CIN 2,3). Women with low-grade CIN have a low potential for developing cervical malignancy, while those with high-grade lesions are at higher risk of progression to malignancy. In managing women with CIN, the goal is to prevent possible progression to invasive cancer while avoiding overtreatment of lesions that are likely to regress.
Choosing a treatment option for CIN and follow-up after treatment is reviewed here. Evaluation and management of low-grade and high-grade CIN is discussed separately. (See "Cervical intraepithelial neoplasia: Management of low-grade and high-grade lesions".)
Other related issues include:
●Cervical cancer screening (see "Screening for cervical cancer")
●Evaluation of abnormal screening tests and diagnosis of CIN (see "Cervical cytology: Evaluation of atypical squamous cells (ASC-US and ASC-H)" and "Cervical cytology: Evaluation of low-grade squamous intraepithelial lesions (LSIL)" and "Cervical cytology: Evaluation of high-grade squamous intraepithelial lesions (HSIL)")
●Techniques for CIN treatment (see "Cervical intraepithelial neoplasia: Procedures for cervical conization" and "Cervical intraepithelial neoplasia: Ablative therapies")
●Reproductive effects of CIN treatment (see "Cervical intraepithelial neoplasia: Reproductive effects of treatment")
●Diagnosis of cervical cancer (see "Invasive cervical cancer: Epidemiology, risk factors, clinical manifestations, and diagnosis")
TREATMENT OPTIONS — The mainstays of treatment of high-grade cervical intraepithelial neoplasia (CIN) are excision and ablation of the transformation zone of the cervix (an anatomic area that contains the transition from the squamous epithelium of the ectocervix to the glandular epithelium of the endocervix). Hysterectomy is an option for women who are incompletely treated with excision or ablation or who have recurrent CIN. Nonsurgical treatments are investigational.
Cervical excision versus ablation — Ablation is rarely performed in the United States because it has few advantages compared with loop electrosurgical excision procedure (LEEP). Both types of procedures can be performed in an office setting and are associated with a low morbidity rate. Excisional procedures provide a diagnostic specimen, which is a significant advantage. There is no evidence that either ablation or excision is more effective, but the available studies have methodologic limitations and do not clearly address CIN 1 and CIN 2,3 separately.
●Excisional treatments are referred to as cone biopsies or cervical conization, because they typically consist of the removal of a cone-shaped specimen that includes the transformation zone and a portion of the endocervix. Cold knife conization (performed with a scalpel) has been largely replaced by LEEP, also called large loop excision of the transformation zone (LLETZ). Laser conization is another technique. Conization techniques and decisions regarding the choice of excisional procedure are discussed separately. (See "Cervical intraepithelial neoplasia: Procedures for cervical conization", section on 'Comparison of methods'.)
●Ablative treatments use an energy source (eg, cryotherapy, laser) to destroy the transformation zone. Ablative techniques and decisions regarding the choice of ablative method are discussed separately. (See "Cervical intraepithelial neoplasia: Ablative therapies", section on 'Choosing an ablation technique'.)
For women who are candidates for either excisional or ablative therapy, the choice of procedure type depends primarily upon whether a diagnostic specimen is needed and on future reproductive risks. There are few high-quality studies comparing the efficacy of excision versus ablation. Additional factors that influence the decision are risk of adverse effects, cost, and convenience.
The sections below review the evidence and clinical considerations regarding the choice of excisional or ablative therapy.
Women with CIN 2,3 — Treatment is required for CIN 2,3, with the exception of selected young women. For young women with CIN 2,3 and an adequate colposcopy, either observation or treatment is acceptable. (See "Cervical intraepithelial neoplasia: Management of low-grade and high-grade lesions", section on 'Management' and "Cervical intraepithelial neoplasia: Management of low-grade and high-grade lesions", section on 'Young women'.)
For most women with CIN 2,3 with an adequate colposcopy, we suggest treatment with excision rather than ablation. In general, LEEP is preferred over cold knife cone because it can be performed in the office setting. For women with CIN 2,3 with an inadequate colposcopy, recurrent CIN 2,3, or endocervical sampling with CIN 2,3, we recommend excision rather than ablation.
Data are limited regarding the efficacy of excision versus ablation for CIN 2,3. However, in our practice, we prefer excision for all women treated for CIN 2,3 because it provides a diagnostic specimen, and these women have a higher risk of progression to invasive disease. (See "Cervical intraepithelial neoplasia: Management of low-grade and high-grade lesions", section on 'Risk of malignant disease'.)
Women with CIN 1 — For women with CIN 1, management is guided by the results of the preceding cytologic testing. For women with CIN 1 with a prior cytologic sample reported as atypical squamous cells of undetermined significance (ASC-US), low-grade squamous cell intraepithelial lesion (LSIL), or normal cytology in the presence of human papillomavirus (HPV) 16 or 18, recommended follow-up is cotesting with cytology and an HPV test at one year. For women with CIN 1 and a preceding cytologic test of high-grade squamous intraepithelial lesion (HSIL) or atypical squamous cells, cannot rule out HSIL (ASC-H), either an excisional procedure or observation with cotesting at 12 months and 24 months are recommended. Women with CIN 1 that persists for at least two years may continue follow-up or may undergo treatment. (See "Cervical intraepithelial neoplasia: Management of low-grade and high-grade lesions", section on 'Low-grade lesions: CIN 1'.)
For women with CIN 1 who undergo treatment, we suggest LEEP rather than conization. LEEP is preferred to conization because LEEP can be performed in an office setting and is associated with less morbidity. (See 'Cervical excision versus ablation' above and 'Future obstetric risks' below.)
Efficacy — The efficacy rate for both ablation and excision is approximately 90 to 95 percent [3,4]. There are few high-quality data comparing excision with ablation, and the randomized trials that exist do not provide information regarding use of these techniques in women with CIN 1 compared with CIN 2,3.
A meta-analysis of randomized trials of treatment in women with any degree of CIN included five trials that compared an excisional method with an ablative method . There were insufficient data to make an overall comparison between excision and ablation.
LEEP was found to superior to cryotherapy in one trial, although the results were not analyzed by CIN grade. In this trial, LEEP resulted in a significantly lower rate of residual disease at 12-month follow-up compared with cryotherapy (3.6 versus 11.2 percent; relative risk 0.32, 95% CI 0.13-0.78); however, this was based on few events (six cases of residual disease in the LEEP group and 18 in the cryotherapy group) .
There was no significant difference in the rate of residual disease between methods in most trials, but the majority of these lacked statistical power. Because of this limitation, it remains unclear whether laser ablation is as effective as conization. In women with high-grade disease, the risk of forgoing diagnostic information and missing a cervical cancer requires that use of any therapy other than excision be supported by high quality evidence.
Diagnostic specimen — The principal difference between the two types of procedures is that no specimen is removed in ablative procedures, and thus, there is no diagnostic information and no information regarding whether disease is present at the margins of the treated area. For this reason, an excisional procedure is required for diagnostic purposes in the following situations:
●High risk of invasive disease – For women in whom cervical cancer is suspected, it is crucial to obtain diagnostic information and evaluation of surgical margins. Use of p-16 staining may improve classification and risk stratification of these lesions. However, reporting of p-16 status is not universally available. (See 'Positive margins' below and "Cervical intraepithelial neoplasia: Management of low-grade and high-grade lesions", section on 'Terminology'.)
The incidence of occult squamous carcinoma and glandular disease detected by conization was illustrated in a study of 1189 patients who underwent LEEP; six patients (0.5 percent) had microinvasive squamous carcinoma and 15 (1.3 percent) had adenocarcinoma in situ . Two (33 percent) of the squamous carcinomas and 10 (67 percent) of the adenocarcinomas in situ were not recognized by cytology and colposcopy. Another series of 3738 women who underwent laser ablation for CIN reported nine cervical cancers (0.24 percent) during follow-up .
●Glandular disease is present – Glandular disease may be located in the transformation zone or endocervical canal and lesions are often not contiguous ("skip lesions"), so colposcopically directed biopsy of the transformation zone is insufficient for diagnosis. As noted in the study of 1189 patients described above, this may result in occult glandular neoplasia . (See "Cervical cytology: Evaluation of atypical and malignant glandular cells".)
●Diagnostic uncertainty – A specimen is needed for diagnosis for patients with inconsistent findings on cytology versus colposcopy, ie, high-grade findings on cervical cytology (ASC-H or HSIL) followed by a colposcopic finding of no lesion or CIN 1. In addition, women with an inadequate colposcopic examination may require a diagnostic excisional biopsy.
Future obstetric risks — Excision has been associated with an increased risk of adverse obstetric outcomes (second trimester pregnancy loss, preterm premature rupture of membranes, preterm delivery) in large observational studies. In clinics in which ablation is not available, LEEP is the preferred excisional method because it appears to be associated with a lower risk of preterm delivery than cold knife conization. These issues are discussed in detail separately. (See "Cervical intraepithelial neoplasia: Reproductive effects of treatment".)
Morbidity — Excisional methods are typically thought to be associated with greater morbidity than ablative therapy. However, the meta-analysis of randomized trials found no significant difference in adverse effects (eg, hemorrhage, pain) and some trials showed a trend toward less morbidity with excisional methods (eg, LEEP versus laser ablation) .
However, women planning a subsequent pregnancy may prefer to take some risk of disease recurrence to offset the risk of preterm delivery. These women should be offered the choice of either laser ablation or excision and counseled about the risks and benefits of each. (See 'Future obstetric risks' above.)
Hysterectomy — Hysterectomy is not a first-line treatment for CIN because the risk of significant morbidity with hysterectomy is higher than with less invasive treatment modalities (excision, ablation). Hysterectomy is reserved for women with CIN 2,3 with a positive conization margin who have completed childbearing and who would benefit from a definitive procedure. For women with a histologic diagnosis of recurrent or persistent CIN 2,3, either a repeat diagnostic excisional procedure or hysterectomy is appropriate. Hysterectomy may be necessary in women with scarring or shortening of the cervix from prior treatments that prohibits a repeat excisional procedure. Scarring may increase the risk of complications of a repeat conization or limit the results of further testing (ie, scarring may obscure premalignant cells). In addition, a definitive procedure is preferable for women who are not willing or able to comply with long-term follow-up.
If invasive disease is suspected, a conization may be performed and sent for frozen section prior to hysterectomy to confirm that cervical cancer is not present and that a radical hysterectomy is not indicated.
Other treatments — Several alternative methods for treatment of CIN have been developed, all of which are currently investigational. Such techniques include photodynamic therapy [8,9], cyclooxygenase-2 inhibitors , vaccines , environmental alterations , use of topical agents (eg, cidofovir, difluoromethylornithine, all-trans retinoic acid, trichloroacetic acid [13-16]), and oral agents .
OUTCOME — Cervical treatments (excisional or ablative) for women with cervical intraepithelial neoplasia (CIN) can reduce the risk of invasive cancer of the cervix by 95 percent in the first eight years after therapy . Most failures occur within two years, but recurrences may occur up to 20 years later [4,19].
The risk of invasive cervical cancer among these women remains greater than that among the general population of women, and the increased risk persists for as long as 20 to 25 years (56 per 100,000 woman-years versus 5.6 per 100,000 woman-years in the general population) [20-25].
Overall, the rate of recurrent or persistent CIN is 5 to 17 percent despite therapy with any of the excisional or ablative techniques . Higher rates of persistent disease are associated with large lesion size (eg, greater than two-thirds of the surface of the cervix) , endocervical gland involvement , positive margin status [28,29], and continuing human papillomavirus (HPV) DNA positivity (especially with HPV 16 ) six months or more posttreatment, while the risk is much lower in the absence of these characteristics [28,31-35].
The prognosis after treatment of CIN differs based upon the presence of CIN at the margin of a conization specimen; the margin status is unknown following ablative therapy.
Negative margins — CIN has a high rate of cure when the entire lesion has been excised. This was illustrated in one of the few studies with long-term follow-up. In this study, 4417 women with CIN 3 and negative margins after cold knife conization were followed with colposcopy, cytology, and pelvic examination for a mean of 18 years (range, 5 to 30 years) :
●New high-grade cytologic or histologic lesions (high-grade squamous intraepithelial lesion on cytology, CIN 2,3) developed in 15 (0.35 percent) patients after a median of 8.9 (range, 3.3 to 16.8) years. In two of these women, high-grade glandular intraepithelial lesions developed 14 and 17 years after conization.
●The remaining 4402 (99.7 percent) patients remained free of high-grade cervical neoplasia.
Positive margins — Studies have consistently shown that patients with a positive margin after an excisional procedure of the cervix are at significantly higher risk for residual disease, as determined at subsequent hysterectomy or with repeat excision, than patients with clear margins [28,36-48]. The outcome in women with positive margins was demonstrated in a meta-analysis of 66 studies involving over 35,000 women who underwent an excisional procedure for any grade of CIN . Follow-up was less than two years in most studies. Compared with women with clear or uncertain margins, women with positive margins were at significantly increased risk of any-grade posttreatment CIN (relative risk [RR] 5.47, 95% CI 4.37-6.83). This effect was also seen if posttreatment CIN 2,3 was used as the endpoint (18 versus 3 percent; RR 6.09, 95% CI 3.87-9.60).
The risk of residual disease is highest if both the excised specimen and the endocervical curettage show high-grade histology [38,41,49]. The risk of residual disease is also increased if both the ecto- and endocervical margins are positive. A study of 390 patients with involved margins after cold-knife conization for CIN 3 reported that the combined risk of persistent, recurrent, or progressive disease when ectocervical, endocervical, or both margins were positive was 17, 21, and 52 percent, respectively, after 6 to 30 years of follow-up . Five patients developed microinvasive disease and one patient developed stage 1B carcinoma.
Negative excisional specimen — A completely negative excisional specimen raises concern that the lesion was missed. The clinical significance of this situation was illustrated by a study in which 14 percent of 674 loop electrosurgical excision procedure (LEEP) specimens performed for biopsy-proven, high-grade CIN had no evidence of CIN . The recurrence rate after a negative LEEP was similar to that after a LEEP with a positive margin (24 versus 27 percent), and 24 percent of these patients had subsequent neoplastic findings, including two carcinomas and eight high-grade lesions, after a median follow-up of two years. These patients should be followed similarly to those with positive margins.
Recurrence — Recurrences in women with positive margins can occur years after treatment. In a retrospective study of women after LEEP, mean time to recurrence in women with positive margins was almost four years .
FOLLOW-UP AFTER TREATMENT
Routine follow-up — The evaluation approach presented here is provided by the 2012 consensus guidelines of the American Society for Colposcopy and Cervical Pathology in collaboration with multiple professional societies and government organizations in the United States and Canada, including the American College of Obstetricians and Gynecologists, Society of Obstetricians and Gynaecologists of Canada, Society of Gynecologic Oncologists, American Cancer Society, Centers for Disease Control and Prevention, and the US Food and Drug Administration. The algorithms for the consensus guidelines can be found online.
After treatment with excision or ablation, women with cervical intraepithelial neoplasia (CIN) 2,3 should be followed with [2,51]:
●Human papillomavirus (HPV)/cervical cytology cotesting at 12 and 24 months.
•If both cotests are negative, cotesting should be repeated in three years. If cotesting is again negative, the patient may resume routine screening.
•If there is abnormal cytology or a positive HPV test during follow-up, colposcopy with endocervical sampling should be performed.
●Routine screening is recommended for at least 20 years even if screening continues beyond age 65 years.
●If CIN 2,3 is identified at the margins of an excisional procedure or postprocedure endocervical curettage (ECC), cytology and ECC at four to six months is preferred, but either repeat excision or hysterectomy may be performed.
Women who have positive margins on the excised specimens or positive findings in the concomitant ECC specimen should be counseled about the risks and benefits of observation versus further treatment, taking into account patient preference and plans for future childbearing [52-54]. (See 'Positive margins' above.)
Observational studies have consistently reported that posttreatment HPV testing at 6 to 12 months post-therapy is highly sensitive (sensitivity, 90 percent ) in identifying persistent/recurrent CIN and more sensitive than cytology (sensitivity, 70 percent ) [4,31-34,55-62]. Whether combined cytology plus HPV testing is superior remains to be proven.
A long-term, multi-cohort study of 435 women treated for CIN 2,3 demonstrated the value of combined cervical cytology and high-risk HPV testing at 6 and 24 months postprocedure; the referral threshold for cytology was either cytology test that was atypical squamous cells (ASC) or worse or a positive HPV test . If both tests were negative at six months, the risk of persistent or recurrent CIN 2,3 was 4.6 percent; if both tests were negative at 6 and 24 months, the risk was 1.8 percent. By contrast, if either test was positive at six months, the risk of persistent CIN 2,3 or worse was 45 to 60 percent, indicating the need for immediate evaluation and treatment for these patients.
Subsequent screening — Women who have a history of CIN 2, CIN 3, or adenocarcinoma in situ and who have been appropriately treated or had spontaneous regression of cervical neoplasia should be routinely screened for at least 20 years following diagnosis, even if this extends screening past age 65 years, based upon guidelines from the American College of Obstetricians and Gynecologists, the American Society for Colposcopy and Cervical Pathology, the American Cancer Society, and the American Society for Clinical Pathology [64,65]. Women with a history of CIN 2,3 in the past 20 years appear to have a 5- to 10-fold higher risk of cervical cancer compared with the general population. This is based upon data from longitudinal studies. One retrospective study included over 37,000 women in a British Columbia, Canada database. At 18 years after treatment, the rate of cervical cancer was higher in women treated for CIN (81 percent with CIN 2,3, the remainder had CIN 1) compared with women without CIN (37 versus 6 per 100,000 woman-years) . In addition, a systematic review of retrospective studies of women treated for CIN reported a rate of cervical cancer of 56 per 100,000 woman-years until 20 years after treatment; only three studies followed women for 16 to 20 years .
While the professional societies' recommendation for prolonged screening applies only to women with CIN 2,3, a major limitation of the data cited above is that they include women treated for CIN 1. Other data show that the risk of cervical cancer following CIN 1 is significantly lower than for CIN 2,3. (See "Cervical intraepithelial neoplasia: Management of low-grade and high-grade lesions", section on 'Risk of malignant disease' and "Cervical intraepithelial neoplasia: Management of low-grade and high-grade lesions", section on 'Risk of malignant disease'.)
An additional challenge regarding screening women with CIN 2,3 for 20 years is that confirmation of this diagnosis is often difficult. Many women do not recall their history over this period of time or may not have been told a specific diagnosis, and medical records are not always accessible. In our practice, we ask all patients about their cervical cancer screening history. If the patient is certain that she had a conization or loop electrosurgical excision procedure, we regard her as having a history of CIN 2,3. If she reports a history of cryotherapy or a history of "an abnormal Pap smear," we regard her history as uncertain. In addition, some women with a history of CIN 2,3 may report a normal screening history. We obtain medical records whenever possible.
Cervical cancer screening is discussed in detail separately. (See "Screening for cervical cancer".)
Special follow-up issues
Delayed treatment — Many women do not follow up promptly after abnormal cervical cytology. In a retrospective study of over 8000 women with abnormal cervical cytology, 19 percent were lost to follow-up, including 8 percent of those with high-grade squamous intraepithelial lesions (HSIL) . During a period of time when a patient is lost to follow-up, lesions may regress or worsen and re-evaluation is often necessary.
When a patient is diagnosed with CIN 2,3 and treatment is delayed, in our practice, we proceed with the planned treatment without re-evaluation if the interval from the time of diagnosis is up to 6 to 12 months. Once the treatment delay has been more than 12 months, we reassess the patient with cervical cytology, colposcopy, biopsy, and ECC. In such cases, the goals of reevaluation are to:
●Exclude the development of a lesion suspicious for microinvasive or invasive carcinoma. In the case of a suspected microinvasive carcinoma, a conization would be indicated. In the case of a gross lesion suspicious for cancer, all that may be needed is a cervical biopsy to confirm the diagnosis, and conization of a gross lesion would and should be avoided.
●Assess the patient for potential resolution of her high-grade lesion. As discussed above, regression is particularly likely in the postpartum patients and young women and particularly important for any young patient who is desirous of future fertility for whom the treatment-associated risk of preterm delivery has to be considered in the context of higher spontaneous regression rates of CIN 2,3. (See "Cervical intraepithelial neoplasia: Management of low-grade and high-grade lesions", section on 'Risk of malignant disease' and "Cervical intraepithelial neoplasia: Management of low-grade and high-grade lesions", section on 'Young women'.)
Posthysterectomy — The risk of vaginal intraepithelial neoplasia (VAIN) or vaginal cancer is extremely low in women who have undergone total hysterectomy (removal of the uterus and cervix) for benign disease (excluding CIN 2,3) and for this reason, screening guidelines in the United States from the US Preventive Services Task Force, the American Cancer Society, and the American College of Obstetricians and Gynecologists concur that most women do not need posthysterectomy vaginal cytology [64,67-69]. Vaginal cytology for vaginal cancer screening is advisable in women with CIN 2,3 prior to, or diagnosed at the time of, total hysterectomy [64,67-70]. The American College of Obstetricians and Gynecologists recommends ongoing screening of these women for at least 20 years after treatment of CIN 2,3 . (See "Screening for cervical cancer", section on 'Prior hysterectomy'.)
Interpretation of vaginal cytology results is discussed separately. (See "Cervical and vaginal cytology: Interpretation of results (Pap test report)", section on 'Vaginal cytology'.)
HPV vaccination in women with CIN — For women and girls who are candidates for human papillomavirus (HPV) vaccination, the United States Centers for Disease Control and Prevention (CDC) recommends vaccination regardless of a history of abnormal cervical cancer screening results or genital warts.
This is discussed detail separately. (See "Recommendations for the use of human papillomavirus vaccines", section on 'Immunization in females with pre-existing cervical abnormalities or genital warts'.)
Vaccination does not have a therapeutic effect on an existing HPV infection or cervical neoplasia. Some data suggest that HPV vaccination is associated with a lower rate of cervical intraepithelial neoplasia (CIN) recurrence. As an example, a retrospective cohort study reported that women who underwent a loop electrosurgical excision procedure (LEEP) and received HPV vaccination were less likely to recur at a median follow-up of 3.5 years, even among women positive for HPV 16 or 18 at baseline (vaccinated: 2.5 versus nonvaccinated: 8.5 percent) .
Management of sexual partners
Male partners — HPV testing in men is not commercially available. Studies of women with CIN have found the following prevalence of associated conditions in their male sexual partners: high-risk HPV infection (58 percent ) and penile intraepithelial neoplasia (9 to 33 percent [73,74]). Randomized trial data show that condom use promotes regression of HPV-associated lesions in women with CIN and their male sexual partners [75,76]. As an example, in a randomized trial, women with CIN and their male sexual partners who did versus did not use condoms had higher rates of regression of CIN lesions (53 versus 35 percent) and clearance of high-risk HPV infection (23 versus 4 percent) .
A detailed discussion of penile premalignant lesions and penile cancer can be found separately. (See "Carcinoma of the penis: Clinical presentation, diagnosis, and staging".)
Female partners — HPV infection occurs in women who have sex with women, including those who have had not sexual contact with men [77,78]. Strategies to prevent persistence and reinfection of HPV have not been identified for women with CIN who have sex with women. (See "Medical care of women who have sex with women".)
Subsequent fertility and pregnancy — Treatment of CIN with ablation or excision may impact subsequent fertility or pregnancy. There are few studies regarding how long women should wait to conceive after treatment.
We suggest an interval of three months or longer from an excisional procedure to conception of a pregnancy. Reproductive effects of CIN treatment are discussed in detail separately. (See "Cervical intraepithelial neoplasia: Reproductive effects of treatment".)
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Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Beyond the Basics topics (see "Patient education: Management of a cervical biopsy with precancerous cells (Beyond the Basics)" and "Patient education: Follow-up of low-grade abnormal Pap tests (Beyond the Basics)" and "Patient education: Follow-up of high-grade abnormal Pap tests (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Cervical intraepithelial neoplasia (CIN) is a premalignant condition of the uterine cervix. CIN refers to squamous, not glandular, abnormalities. (See 'Introduction' above.)
●The mainstays of treatment of CIN are excision or ablation of the transformation zone of the cervix (an anatomic area that contains the transition from the squamous epithelium of the ectocervix to the glandular epithelium of the endocervix). Hysterectomy is an option for women who are incompletely treated with excision or ablation. (See 'Treatment options' above.)
●For women with CIN 1, follow-up is required. Women with CIN 1 that persists for at least two years may continue follow-up or may undergo treatment. For women with CIN 1 who undergo treatment, we suggest loop electrosurgical excision (LEEP) rather than conization or ablation (Grade 2C). (See "Cervical intraepithelial neoplasia: Management of low-grade and high-grade lesions".)
●For most women with CIN 2,3 with an adequate colposcopy, we suggest treatment with excision rather than ablation (Grade 2B). For women with CIN 2,3 with an inadequate colposcopy, recurrent CIN 2,3, or endocervical sampling with CIN 2,3, we recommend excision rather than ablation (Grade 1B). (See "Cervical intraepithelial neoplasia: Management of low-grade and high-grade lesions".)
●Hysterectomy is not a first-line treatment for CIN. Hysterectomy is a reasonable option only for women with CIN 2,3 who have a positive conization margin, who have completed childbearing, and who value a definitive procedure more than avoiding potential operative complications. (See 'Hysterectomy' above.)
●Cervical treatments (excision or ablation) reduce the risk of invasive cancer of the cervix by 95 percent in the first eight years after therapy. Most failures occur within two years, but recurrences may occur up to 20 years later. (See 'Outcome' above and 'Subsequent screening' above.)
●After treatment with excision or ablation, women with CIN 2,3 should be followed with human papillomavirus (HPV) and cervical cytology cotesting in 12 and 24 months. (See 'Follow-up after treatment' above.)
●Patients with positive conization margins are at sixfold risk of residual disease. (See 'Positive margins' above.)
●For women and girls who are candidates for HPV vaccination, a diagnosis of CIN is not a contraindication because the vaccine may protect against viral types to which the patient has not yet been exposed. (See 'HPV vaccination in women with CIN' above.)
ACKNOWLEDGMENT — The authors and editors would like to recognize Dr. Christine Holschneider, who contributed to previous versions of this topic review.
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- Montz FJ. Management of high-grade cervical intraepithelial neoplasia and low-grade squamous intraepithelial lesion and potential complications. Clin Obstet Gynecol 2000; 43:394.
- Massad LS, Einstein MH, Huh WK, et al. 2012 updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors. J Low Genit Tract Dis 2013; 17:S1.
- Martin-Hirsch PP, Paraskevaidis E, Bryant A, Dickinson HO. Surgery for cervical intraepithelial neoplasia. Cochrane Database Syst Rev 2013; :CD001318.
- Paraskevaidis E, Arbyn M, Sotiriadis A, et al. The role of HPV DNA testing in the follow-up period after treatment for CIN: a systematic review of the literature. Cancer Treat Rev 2004; 30:205.
- Chirenje ZM, Rusakaniko S, Akino V, Mlingo M. A randomised clinical trial of loop electrosurgical excision procedure (LEEP) versus cryotherapy in the treatment of cervical intraepithelial neoplasia. J Obstet Gynaecol 2001; 21:617.
- Ferenczy A, Choukroun D, Arseneau J. Loop electrosurgical excision procedure for squamous intraepithelial lesions of the cervix: advantages and potential pitfalls. Obstet Gynecol 1996; 87:332.
- Pearson SE, Whittaker J, Ireland D, Monaghan JM. Invasive cancer of the cervix after laser treatment. Br J Obstet Gynaecol 1989; 96:486.
- Yamaguchi S, Tsuda H, Takemori M, et al. Photodynamic therapy for cervical intraepithelial neoplasia. Oncology 2005; 69:110.
- Bodner K, Bodner-Adler B, Wierrani F, et al. Cold-knife conization versus photodynamic therapy with topical 5-aminolevulinic acid (5-ALA) in cervical intraepithelial neoplasia (CIN) II with associated human papillomavirus infection: a comparison of preliminary results. Anticancer Res 2003; 23:1785.
- Hefler LA, Grimm C, Speiser P, et al. The cyclooxygenase-2 inhibitor rofecoxib (Vioxx) in the treatment of cervical dysplasia grade II-III A phase II trial. Eur J Obstet Gynecol Reprod Biol 2006; 125:251.
- Garcia F, Petry KU, Muderspach L, et al. ZYC101a for treatment of high-grade cervical intraepithelial neoplasia: a randomized controlled trial. Obstet Gynecol 2004; 103:317.
- Velema JP, Ferrera A, Figueroa M, et al. Burning wood in the kitchen increases the risk of cervical neoplasia in HPV-infected women in Honduras. Int J Cancer 2002; 97:536.
- Vlastos AT, West LA, Atkinson EN, et al. Results of a phase II double-blinded randomized clinical trial of difluoromethylornithine for cervical intraepithelial neoplasia grades 2 to 3. Clin Cancer Res 2005; 11:390.
- Ruffin MT, Bailey JM, Normolle DP, et al. Low-dose topical delivery of all-trans retinoic acid for cervical intraepithelial neoplasia II and III. Cancer Epidemiol Biomarkers Prev 2004; 13:2148.
- Van Pachterbeke C, Bucella D, Rozenberg S, et al. Topical treatment of CIN 2+ by cidofovir: results of a phase II, double-blind, prospective, placebo-controlled study. Gynecol Oncol 2009; 115:69.
- Geisler S, Speiser S, Speiser L, et al. Short-Term Efficacy of Trichloroacetic Acid in the Treatment of Cervical Intraepithelial Neoplasia. Obstet Gynecol 2016; 127:353.
- Del Priore G, Gudipudi DK, Montemarano N, et al. Oral diindolylmethane (DIM): pilot evaluation of a nonsurgical treatment for cervical dysplasia. Gynecol Oncol 2010; 116:464.
- Soutter WP, de Barros Lopes A, Fletcher A, et al. Invasive cervical cancer after conservative therapy for cervical intraepithelial neoplasia. Lancet 1997; 349:978.
- Jakobsson M, Gissler M, Paavonen J, Tapper AM. Long-term mortality in women treated for cervical intraepithelial neoplasia. BJOG 2009; 116:838.
- Kalliala I, Anttila A, Pukkala E, Nieminen P. Risk of cervical and other cancers after treatment of cervical intraepithelial neoplasia: retrospective cohort study. BMJ 2005; 331:1183.
- Soutter WP, Sasieni P, Panoskaltsis T. Long-term risk of invasive cervical cancer after treatment of squamous cervical intraepithelial neoplasia. Int J Cancer 2006; 118:2048.
- Wang SS, Sherman ME, Hildesheim A, et al. Cervical adenocarcinoma and squamous cell carcinoma incidence trends among white women and black women in the United States for 1976-2000. Cancer 2004; 100:1035.
- Strander B, Andersson-Ellström A, Milsom I, Sparén P. Long term risk of invasive cancer after treatment for cervical intraepithelial neoplasia grade 3: population based cohort study. BMJ 2007; 335:1077.
- Melnikow J, McGahan C, Sawaya GF, et al. Cervical intraepithelial neoplasia outcomes after treatment: long-term follow-up from the British Columbia Cohort Study. J Natl Cancer Inst 2009; 101:721.
- Rebolj M, Helmerhorst T, Habbema D, et al. Risk of cervical cancer after completed post-treatment follow-up of cervical intraepithelial neoplasia: population based cohort study. BMJ 2012; 345:e6855.
- Mitchell MF, Tortolero-Luna G, Cook E, et al. A randomized clinical trial of cryotherapy, laser vaporization, and loop electrosurgical excision for treatment of squamous intraepithelial lesions of the cervix. Obstet Gynecol 1998; 92:737.
- Demopoulos RI, Horowitz LF, Vamvakas EC. Endocervical gland involvement by cervical intraepithelial neoplasia grade III. Predictive value for residual and/or recurrent disease. Cancer 1991; 68:1932.
- Ghaem-Maghami S, Sagi S, Majeed G, Soutter WP. Incomplete excision of cervical intraepithelial neoplasia and risk of treatment failure: a meta-analysis. Lancet Oncol 2007; 8:985.
- Manchanda R, Baldwin P, Crawford R, et al. Effect of margin status on cervical intraepithelial neoplasia recurrence following LLETZ in women over 50 years. BJOG 2008; 115:1238.
- Gök M, Coupé VM, Berkhof J, et al. HPV16 and increased risk of recurrence after treatment for CIN. Gynecol Oncol 2007; 104:273.
- Paraskevaidis E, Koliopoulos G, Alamanos Y, et al. Human papillomavirus testing and the outcome of treatment for cervical intraepithelial neoplasia. Obstet Gynecol 2001; 98:833.
- Nagai Y, Maehama T, Asato T, Kanazawa K. Persistence of human papillomavirus infection after therapeutic conization for CIN 3: is it an alarm for disease recurrence? Gynecol Oncol 2000; 79:294.
- Chua KL, Hjerpe A. Human papillomavirus analysis as a prognostic marker following conization of the cervix uteri. Gynecol Oncol 1997; 66:108.
- Nobbenhuis MA, Meijer CJ, van den Brule AJ, et al. Addition of high-risk HPV testing improves the current guidelines on follow-up after treatment for cervical intraepithelial neoplasia. Br J Cancer 2001; 84:796.
- Kaufman RH. Is there a role for human papillomavirus testing in clinical practice? Obstet Gynecol 2001; 98:724.
- Reich O, Pickel H, Lahousen M, et al. Cervical intraepithelial neoplasia III: long-term outcome after cold-knife conization with clear margins. Obstet Gynecol 2001; 97:428.
- Paterson-Brown S, Chappatte OA, Clark SK, et al. The significance of cone biopsy resection margins. Gynecol Oncol 1992; 46:182.
- Felix JC, Muderspach LI, Duggan BD, Roman LD. The significance of positive margins in loop electrosurgical cone biopsies. Obstet Gynecol 1994; 84:996.
- Park JY, Lee SM, Yoo CW, et al. Risk factors predicting residual disease in subsequent hysterectomy following conization for cervical intraepithelial neoplasia (CIN) III and microinvasive cervical cancer. Gynecol Oncol 2007; 107:39.
- Mohamed-Noor K, Quinn MA, Tan J. Outcomes after cervical cold knife conization with complete and incomplete excision of abnormal epithelium: a review of 699 cases. Gynecol Oncol 1997; 67:34.
- Husseinzadeh N, Shbaro I, Wesseler T. Predictive value of cone margins and post-cone endocervical curettage with residual disease in subsequent hysterectomy. Gynecol Oncol 1989; 33:198.
- Lapaquette TK, Dinh TV, Hannigan EV, et al. Management of patients with positive margins after cervical conization. Obstet Gynecol 1993; 82:440.
- Livasy CA, Maygarden SJ, Rajaratnam CT, Novotny DB. Predictors of recurrent dysplasia after a cervical loop electrocautery excision procedure for CIN-3: a study of margin, endocervical gland, and quadrant involvement. Mod Pathol 1999; 12:233.
- Phelps JY 3rd, Ward JA, Szigeti J 2nd, et al. Cervical cone margins as a predictor for residual dysplasia in post-cone hysterectomy specimens. Obstet Gynecol 1994; 84:128.
- Lopes A, Morgan P, Murdoch J, et al. The case for conservative management of "incomplete excision" of CIN after laser conization. Gynecol Oncol 1993; 49:247.
- Maluf PJ, Adad SJ, Murta EF. Outcome after conization for cervical intraepithelial neoplasia grade III: relation with surgical margins, extension to the crypts and mitoses. Tumori 2004; 90:473.
- Moore BC, Higgins RV, Laurent SL, et al. Predictive factors from cold knife conization for residual cervical intraepithelial neoplasia in subsequent hysterectomy. Am J Obstet Gynecol 1995; 173:361.
- Kalogirou D, Antoniou G, Karakitsos P, et al. Predictive factors used to justify hysterectomy after loop conization: increasing age and severity of disease. Eur J Gynaecol Oncol 1997; 18:113.
- Reich O, Lahousen M, Pickel H, et al. Cervical intraepithelial neoplasia III: long-term follow-up after cold-knife conization with involved margins. Obstet Gynecol 2002; 99:193.
- Livasy CA, Moore DT, Van Le L. The clinical significance of a negative loop electrosurgical cone biopsy for high-grade dysplasia. Obstet Gynecol 2004; 104:250.
- http://www.asccp.org/ (Accessed on March 22, 2012).
- Murdoch JB, Morgan PR, Lopes A, Monaghan JM. Histological incomplete excision of CIN after large loop excision of the transformation zone (LLETZ) merits careful follow up, not retreatment. Br J Obstet Gynaecol 1992; 99:990.
- Monk A, Pushkin SF, Nelson AL, Gunning JE. Conservative management of options for patients with dysplasia involving endocervical margins of cervical cone biopsy specimens. Am J Obstet Gynecol 1996; 174:1695.
- Buxton EJ, Luesley DM, Wade-Evans T, Jordan JA. Residual disease after cone biopsy: completeness of excision and follow-up cytology as predictive factors. Obstet Gynecol 1987; 70:529.
- Wright TC Jr, Massad LS, Dunton CJ, et al. 2006 consensus guidelines for the management of women with cervical intraepithelial neoplasia or adenocarcinoma in situ. Am J Obstet Gynecol 2007; 197:340.
- American College of Obstetricians and Gynecologists. ACOG Practice Bulletin number 66, September 2005. Management of abnormal cervical cytology and histology. Obstet Gynecol 2005; 106:645.
- Zielinski GD, Bais AG, Helmerhorst TJ, et al. HPV testing and monitoring of women after treatment of CIN 3: review of the literature and meta-analysis. Obstet Gynecol Surv 2004; 59:543.
- Zielinski GD, Rozendaal L, Voorhorst FJ, et al. HPV testing can reduce the number of follow-up visits in women treated for cervical intraepithelial neoplasia grade 3. Gynecol Oncol 2003; 91:67.
- Chao A, Lin CT, Hsueh S, et al. Usefulness of human papillomavirus testing in the follow-up of patients with high-grade cervical intraepithelial neoplasia after conization. Am J Obstet Gynecol 2004; 190:1046.
- Houfflin Debarge V, Collinet P, Vinatier D, et al. Value of human papillomavirus testing after conization by loop electrosurgical excision for high-grade squamous intraepithelial lesions. Gynecol Oncol 2003; 90:587.
- Coupé VM, Berkhof J, Verheijen RH, Meijer CJ. Cost-effectiveness of human papillomavirus testing after treatment for cervical intraepithelial neoplasia. BJOG 2007; 114:416.
- Park JY, Kim DY, Kim JH, et al. Human papillomavirus test after conization in predicting residual disease in subsequent hysterectomy specimens. Obstet Gynecol 2009; 114:87.
- Kocken M, Helmerhorst TJ, Berkhof J, et al. Risk of recurrent high-grade cervical intraepithelial neoplasia after successful treatment: a long-term multi-cohort study. Lancet Oncol 2011; 12:441.
- Committee on Practice Bulletins—Gynecology. ACOG Practice Bulletin Number 131: Screening for cervical cancer. Obstet Gynecol 2012; 120:1222.
- Saslow D, Solomon D, Lawson HW, et al. American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer. CA Cancer J Clin 2012; 62:147.
- Singhal R, Rubenstein LV, Wang M, et al. Variations in practice guideline adherence for abnormal cervical cytology in a county healthcare system. J Gen Intern Med 2008; 23:575.
- Saslow D, Runowicz CD, Solomon D, et al. American Cancer Society guideline for the early detection of cervical neoplasia and cancer. CA Cancer J Clin 2002; 52:342.
- US Preventive Services Task Force. Screening for cervical cancer: recommendations and rationale. Agency for Healthcare Research and Quality, Rockville, MD 2003. www.ahrq.gov/clinic/3rduspstf/cervcan/cervcanrr.pdf (Accessed on October 11, 2011).
- Stokes-Lampard H, Wilson S, Waddell C, et al. Vaginal vault smears after hysterectomy for reasons other than malignancy: a systematic review of the literature. BJOG 2006; 113:1354.
- Schockaert S, Poppe W, Arbyn M, et al. Incidence of vaginal intraepithelial neoplasia after hysterectomy for cervical intraepithelial neoplasia: a retrospective study. Am J Obstet Gynecol 2008; 199:113.e1.
- Kang WD, Choi HS, Kim SM. Is vaccination with quadrivalent HPV vaccine after loop electrosurgical excision procedure effective in preventing recurrence in patients with high-grade cervical intraepithelial neoplasia (CIN2-3)? Gynecol Oncol 2013; 130:264.
- Bleeker MC, Hogewoning CJ, Berkhof J, et al. Concordance of specific human papillomavirus types in sex partners is more prevalent than would be expected by chance and is associated with increased viral loads. Clin Infect Dis 2005; 41:612.
- Aynaud O, Ionesco M, Barrasso R. Penile intraepithelial neoplasia. Specific clinical features correlate with histologic and virologic findings. Cancer 1994; 74:1762.
- Barrasso R, De Brux J, Croissant O, Orth G. High prevalence of papillomavirus-associated penile intraepithelial neoplasia in sexual partners of women with cervical intraepithelial neoplasia. N Engl J Med 1987; 317:916.
- Hogewoning CJ, Bleeker MC, van den Brule AJ, et al. Condom use promotes regression of cervical intraepithelial neoplasia and clearance of human papillomavirus: a randomized clinical trial. Int J Cancer 2003; 107:811.
- Bleeker MC, Hogewoning CJ, Voorhorst FJ, et al. Condom use promotes regression of human papillomavirus-associated penile lesions in male sexual partners of women with cervical intraepithelial neoplasia. Int J Cancer 2003; 107:804.
- Marrazzo JM, Koutsky LA, Kiviat NB, et al. Papanicolaou test screening and prevalence of genital human papillomavirus among women who have sex with women. Am J Public Health 2001; 91:947.
- Marrazzo JM, Koutsky LA, Stine KL, et al. Genital human papillomavirus infection in women who have sex with women. J Infect Dis 1998; 178:1604.