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 if necessary, colposcopic biopsies should be taken for histopathological examination. 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 conformity between colposcopic biopsy and postoperative pathology, which is questioned.
3. Histopathological examination: it is the “gold standard” for determining CIN or cervical cancer. 1) Cervical biopsy: histopathological diagnosis is the gold standard for confirming CIN. Select colposcopic biopsy of suspicious lesions and, if necessary, multi-point biopsy or biopsy of unstained areas by iodine test to improve the diagnosis rate. 2) ECC by cervical canal scratching: ECC can help to identify occult cervical invasive cancer. ECC can be chosen in the following cases: suspicious lesions in the cervical canal (e.g. high vaginal drainage, cervical canal dilatation, 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, ECC is contraindicated during colposcopy in pregnancy.3) Diagnostic conical hysterectomy: see the guidelines specified by the 2006 ASCCP for indications: (i) CIN1 on histological biopsy with unsatisfactory colposcopy; (ii) CIN1 on histological biopsy with lesions persisting for more than 1 year; (iii) HSIL (CIN2/3 and CIS in situ) confirmed by histological biopsy; (iv) three step technique with inconsistent diagnostic results; ⑤ those with ECC suggesting positive lesions in the cervical canal; ⑥ those with positive cut margins of conization specimens (4-6 months colposcopic follow-up or ECC is preferred, repeat conization is also possible); ⑦ those with high suspicion of invasive cancer during pregnancy (only diagnostic cervical excision is advocated, not major conization, LEEP or cold knife conization is recommended). 4) Scraping. Scraping is feasible in ≥35-year-old AGC patients with suspected endometrial lesions.
II. Treatment
The principle of individualized treatment is emphasized. Treatment is based on 1) CIN level; 2) lesion site and extent; 3) age and physiological requirements for fertility; 4) previous cytology results; 5) high-risk HPV DNA test results; 6) medical resources, technical level, and physician experience; 7) follow-up conditions; and 8) special populations.
1. CIN1 Treatment.
Treatment principle: follow-up is the main focus, with discretionary treatment. For CIN1 diagnosed by histology, the medical history and colposcopic images should be reviewed again, and a comprehensive consideration should be made based on cytology, HPV DNA test results and type of migratory zone, patient age, reproductive requirements, and the presence of obvious abnormal colposcopic manifestations.
(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 cervical biopsy should be performed.
5) Young people with fertility requirements can be followed up regularly with cytology and colposcopy for a period of 24 months.
(6) Key points of management of CIN1 lesions involving glands: It is recommended to follow CIN2/3 and not to follow up alone.
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 HPV DNA at month 12. further colposcopy should be performed if the cytology results are ASC and higher grade lesions or if HPV DNA is positive. If two repeat cytology smear results are negative, or 1 negative HPV DNA, 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 will be done; if the cytology result is still ASC or above change at month 24, colposcopy will be done. Follow up by HPV DNA 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 prior to 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 ablation. 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, Treatment of CIN2/3.
Treatment principles
(1) For patients with satisfactory colposcopic findings of CIN2/3, hysterectomy or ablation of the cervical lesion 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 to obtain a pathological diagnosis of the excised specimen and reduces the risk of missed diagnosis of occult invasive carcinoma.
(2) In patients with CIN 2/3 with unsatisfactory colposcopic findings, diagnostic cervical conization excision is now mostly recommended because there is up to a 7% chance of occult invasive carcinoma, which can be detected during diagnostic cervical conization.
Key points for 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. HPV DNA testing at an interval of at least 6 months may be chosen as the follow-up method. Colposcopy with ECC is recommended if positive for high-risk HPV DNA. routine screening follow-up is available for negative HPV DNA test results. A colposcopic evaluation is required at 6 and 12 months after treatment, and concurrent ECC is recommended.
2) In cases of tissue margin involvement after cervical conization, colposcopy with concomitant ECC is preferable for follow-up at 4-6 months interval. For patients who opt for further treatment, repeat cervical lesion excision may be performed. Total hysterectomy is used only in cases where repeat hysterectomy for cervical lesions is not appropriate.
(3) CIN2/3 in pregnancy rarely develops into invasive carcinoma and has a high rate of spontaneous regression after delivery. In contrast, CIN during pregnancy has a high rate of surgical complications; (i) severe intraoperative bleeding; and (ii) low chance of complete excision of the lesion, leading to a high recurrence rate or the presence of persistent lesions. 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 treatment and regular follow-up can be performed; for those diagnosed with CIN2, follow-up observation 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 findings and normal colposcopy results can enter the routine screening cycle. If colposcopy reveals aggravation of the lesion or cytology of Pap grade III or higher or HSIL, or if the colposcopic lesion persists for 1 year, a repeat biopsy is recommended; if the histopathological diagnosis is CIN3 or if CIN2/3 has persisted for 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 result of HPV DNA is not appropriate.