CIN is quite common in women of reproductive age, and inappropriate management of CIN may increase the risk of cervical cancer, or overtreatment may lead to complications. Therefore, scientific and reasonable management of CIN is a key component of cervical cancer prevention.
I. Diagnosis
The standardized diagnosis procedure of CIN is “cytology-colposcopy-histopathology”.
Cervical cytology is the first step in the “three-step” diagnosis of cervical lesions, and the management of abnormal epithelial cells in TBS can be referred to the guidelines of the American Society for Colposcopy and Cervical Pathology (ASCCP) in 2006; colposcopy is required for Pap smear grade II and above, and colposcopic biopsy is required if necessary. Histopathology.
Colposcopy: This is the key step in the “three-stage” diagnosis. It involves observation of the transformation zone, epithelium and blood vessels, observation of acetic acid and iodine tests, and biopsy of the lesion. There are two main problems; one is the misuse of colposcopy; the other is the low rate of compliance between colposcopic biopsy and postoperative pathology, which is questioned.
3.Histopathological examination: It is the “gold standard” to determine CIN or cervical cancer.
(1) Cervical biopsy: histopathological diagnosis is the gold standard for confirming CIN. Select colposcopic biopsies of suspicious lesions and, if necessary, multi-point biopsies or biopsies of unstained areas by iodine test to improve the diagnosis rate.
(2) ECC by cervical canal scratching: ECC can help to identify occult invasive cervical cancer. ECC can be chosen in the following cases: suspicious lesions in the cervical canal (e.g. high vaginal drainage, enlarged cervical canal, etc.); Pap grade III or higher or HSIL with satisfactory colposcopic images/no lesions seen; when colposcopic images are unsatisfactory at follow-up colposcopy after treatment for CIN2/3. In principle, colposcopy during pregnancy is contraindicated for ECC.
(3) Diagnostic conical hysterectomy: For indications, see the 2006 ASCCP designated guidelines for.
(i) If the histological biopsy is CIN1 and colposcopy is unsatisfactory;
(ii) CIN1 on histologic biopsy with persistent lesions for more than 1 year;
③ Those with a confirmed diagnosis of HSIL (CIN2/3 and carcinoma in situ CIS) on histological biopsy;
④Those with inconsistent diagnostic results of the three-step technique;
(⑤) ECC indicates positive lesions in the cervical canal;
(6) Those with positive cut margins of cone specimens (4-6 months colposcopic follow-up or ECC is preferred, or repeat cones can be performed);
(7) Those with high suspicion of invasive cancer during pregnancy (only diagnostic hysterectomy is advocated, not major conization, LEEP or cold knife conization is recommended).
(4) Scraping: Scraping is feasible in patients ≥35 years old with AGC suspected of endometrial lesions.
II. Treatment
The principle of individualized treatment is emphasized. Treatment is based on.
(1) CIN grade;
(2) site and extent of lesion;
(3) Age and physiological requirements for fertility;
(4) Prior cytologic findings;
(5) High-risk HPVDNA test results;
(6) Medical resources, technical level, and physician experience;
(7) Follow-up conditions;
(8) Special population.
1, CIN1 treatment.
Treatment principles: follow-up is the main focus and treatment is discretionary. For CIN1 diagnosed by histology, the medical history and colposcopic images should be reviewed again, and comprehensive consideration should be made based on cytology, HPVDNA test results and type of migratory zone, patient’s age, reproductive requirements, and the presence of obvious abnormal colposcopic presentations.
(1) If the cytology is HSIL or AGC-AOS and colposcopic images do not exclude cervical invasive carcinoma, cervical cone biopsy should be performed.
(2) If colposcopic images are satisfactory and no special abnormalities are seen, follow-up or laser vaporization treatment can be performed.
(3) If colposcopic images are unsatisfactory and no special abnormalities are seen, cervical canal scratch biopsy should be performed.
(4) If the colposcopic images are unsatisfactory and there are abnormal colposcopic images and there may be more serious lesions, conical biopsy of the cervix is recommended.
(5) Young people with fertility requirements can be followed up regularly with cytology and colposcopy for a period of 24 months.
(6) Key points in the management of CIN1 lesions involving glands: It is recommended to follow CIN2/3 and not to simply follow up.
Key points of follow-up.
(1) If colposcopic findings (images) are satisfactory and no higher grade CIN is seen, follow-up is optional with repeat cytology at months 6 and 12 and repeat high risk HPVDNA at month 12. If cytology results are ASC and higher grade lesions or positive HPVDNA, further colposcopy should be performed. If two repeat cytology smear results are negative, or 1 negative HPVDNA, refer to routine follow-up.
(2) Pregnant women: CIN1 with unsatisfactory colposcopy results may be followed up regularly.
(3) Adolescent (≤20 years) and young women: 12-month repeat cytologic follow-up is used. If the cytology result is HSIL or above at month 12, colposcopy is done; if the cytology result is still ASC or above change at month 24, colposcopy is done. Follow-up by HPVDNA testing method is not advisable.
Precautions.
(1) For CIN1 confirmed by biopsy, the treatment options include ablation or excision of cervical lesions, but cervical canal scraping should be performed before treatment.
(2) For CIN1 that recurs after treatment with ablation, cervical lesion excision is the best option.
(3) For CIN1 with unsatisfactory colposcopic findings, focal resection is preferable to ablative treatment. This is because there may be occult high-grade CIN or lesions in the cervical canal, and the detection rate of CIN2, CIN3 is 10% in the cone specimens of such patients.
(4) Hysterectomy should not be used as the first and main treatment.
2. Management of CIN2/3.
Treatment principles
(1) For patients with satisfactory colposcopic findings of CIN2/3, hysterectomy or ablation of cervical lesions can be chosen after excluding invasive cancer. To ensure efficacy, this operation should remove the entire migratory zone, not just the colposcopically visible lesion. Cervical lesion excision allows obtaining a pathological diagnosis of the excised specimen and reduces the risk of missing occult invasive carcinoma.
(2) In patients with CIN 2/3 with unsatisfactory colposcopic findings, diagnostic cervical conization resection is currently recommended because there is up to a 7% chance of occult invasive carcinoma, which can be detected during diagnostic cervical conization.
Key points of follow-up
(1) For 2/3 of patients after treatment, follow-up can be done by cytology or a combination of cytology and colposcopy at an interval of 4-6 months. If cytology follow-up is used and the result is ≥ASC, further colposcopy with ECC is performed. 2 consecutive negative cytology results may be followed up with routine cytology screening. HPVDNA testing at an interval of at least 6 months may be chosen as the follow-up method. Colposcopy with ECC is recommended if high-risk HPVDNA is positive. routine screening follow-up is available for negative HPVDNA test results. A colposcopic evaluation is required at 6 and 12 months after treatment, and concurrent ECC is recommended.
(2) In cases with marginal tissue involvement after cervical conization, follow-up with colposcopy along with ECC at an interval of 4-6 months is preferred. For patients who opt for further treatment, repeat cervical lesion excision may be performed. Total hysterectomy is used only in cases where repeat hysterectomy of the cervical lesion is not appropriate.
(3) CIN2/3 in pregnancy rarely develops into invasive cancer and has a high rate of spontaneous regression after delivery. In contrast, the incidence of surgical complications of CIN in pregnancy is high;
(1) severe intraoperative bleeding;
(ii) low chance of complete resection of the lesion, leading to a high recurrence rate or persistent lesion presence. Therefore, in principle, treatment of CIN during pregnancy should be avoided; the only indication for cervical conization during pregnancy is the suspected diagnosis of invasive cervical cancer. Colposcopy is performed to exclude cervical invasive carcinoma and follow-up is performed, with further management at a follow-up visit 6 weeks after termination of pregnancy. If the diagnosis of invasive carcinoma is made, the treatment protocol for cervical cancer in pregnancy will be followed.
(4) For CIN2/3 in adolescence, both cervical conization and regular follow-up are possible; for those diagnosed with CIN2, follow-up is preferred; for those diagnosed with CIN3 or those with unsatisfactory colposcopic images, cervical conization is preferred. For regular follow-up, colposcopy and cytology are recommended at 6-month intervals, with a time limit of no more than 24 months; those with 2 negative cytology results and normal colposcopy findings may enter the routine screening cycle. If colposcopy reveals aggravated lesions or cytology of Pap grade III or higher or HSIL, or if colposcopic lesions persist for 1 year, a repeat biopsy is recommended; if the histopathological diagnosis is CIN3 or if CIN2/3 has persisted for up to 24 months from the initial diagnosis, cervical conization is recommended.
Precautions
(1) CIN2/3 should not be observed by serial cytology and colposcopy, except in special populations.
(2) Total hysterectomy should not be used as the primary or initial treatment for CIN2 and CIN3.
(3) Repeat conization or total hysterectomy based on 1 positive HPVDNA result is not appropriate.