Cervical intraepithelial neoplasia

　　First, etiology

　　1. Human papillomavirus infection:In recent years, with the continuous deepening of research on the relationship between human papillomavirus (HPV) infection and the lower genital tract, it has been found that HPV infection is associated with the occurrence of cervical precancerous lesions. HPV infection, as a special type of sexually transmitted disease, is a cause of CIN. Molecular biology and epidemiological studies have shown that human papillomavirus has carcinogenic potential. HPV can be classified into different types based on its carcinogenicity: HPV16, 18, 45, 56 are high-risk types, HPV31, 33, 35, and 11 other types are intermediate-risk types, and HPV6, 11, 26, and 8 other types are low-risk types. CINⅠ and subclinical HPV infection are often caused by HPV6 and 11 types, while 80% of CINⅢ is caused by HPV16 type infection.

　　In cases of severe atypical hyperplasia of the uterine cervix, the cells often have integrated HPV genes, thereby initiating the E1 and E2 genes, leading to the expression of viral genes within the cervical epithelium. Subsequently, the E6 and E7 genes encode multifunctional proteins that interfere with cell growth, playing an important role in the carcinogenic process of high-risk HPV types 16 and 18. The high-risk HPV E6 protein can bind to the tumor suppressor gene p53, causing p53 degradation. The product of the E7 gene is a nuclear phosphoprotein that binds to the tumor suppressor gene retinoblastoma (PRb), leading to its inactivation and thus affecting its inhibitory effect on cell growth.

　　2. Other factors

　　(1) Smoking: Smoking is related to the occurrence of CIN, and its metabolite nicotine, similar to that causing lung cancer, plays an important role in the occurrence of CIN by exerting a刺激性 effect on the cervix.

　　(2) Microbial infection: Gonococcus, Herpes simplex virus (HSV), and trichomoniasis infections can increase susceptibility to HPV, thereby being related to the occurrence of cervical intraepithelial neoplasia (CIN).

　　(3) Endogenous and exogenous immune defects: The infection of immune deficiency viruses can increase the occurrence of CIN, such as in Hodgkin's disease, leukemia, collagen vascular disease, and HPV infectious diseases.

　　Second, Pathogenesis

　　1. Cervical atypical hyperplasia:The atypical hyperplastic cells of squamous epithelium have both atypia and differentiation ability. The microscopic characteristics are: ① The cell nuclei are enlarged and deeply stained, with uneven size and shape; ② The chromatin increases and becomes coarse; ③ The nuclear-cytoplasmic ratio increases; ④ The number of nuclear divisions increases; ⑤ The cell polarity is disordered or disappears. According to the degree of cell atypia and the extent of epithelial involvement, cervical atypical hyperplasia is divided into mild, moderate, and severe degrees (or grades).

　　(1) Mild atypical hyperplasia (or grade I): The cell atypia is slight, and the abnormal proliferating cells are limited to the lower 1/3 of the epithelial layer, with normal cells in the middle and superficial layers.

　　(2) Moderate atypical hyperplasia (or grade II): The cell atypia is obvious, and the abnormal proliferating cells are limited to the lower 2/3 of the epithelial layer, without involving the surface layer.

　　(3) Severe atypical hyperplasia (or grade III): The cell atypia is significant, and the abnormal proliferating cells occupy more than 2/3 of the epithelium or reach the full layer.

　　2. Cervical condyloma is histologically divided into 3 types:

　　(1) Exophytic type, showing papillary growth under the microscope.

　　(2) Endophytic type, the epithelium grows into the stroma.

　　(3) Flat type, the most common type, lacking the characteristics of the above two types, but the cells have atypical changes, easy to be misdiagnosed as CIN.

　　The main microscopic characteristics described by Meisels et al. for the first time were:

　　(1) Empty cells appear in the superficial layer of the epithelium, the cells increase in size, the nucleus shows atypia, and double nuclei or multinuclei can be seen. There are irregular halo areas around the nucleus, while the peripheral cytoplasm is dense.

　　(2) Acanthosis.

　　(3) Overkeratinization or incomplete keratinization cells are visible on the surface layer.

　　(4) Papillary proliferation of the stroma protrudes to the surface. Among them,挖空细胞 are the most typical manifestation of HPV. In 1981, the author pointed out again that挖空细胞 is the main differential point between condyloma acuminatum and atypical hyperplasia, and described the histological manifestations of挖空细胞 in detail.

　　3. Cervical in situ carcinoma

　　(1) The basic characteristics of cervical in situ squamous cell carcinoma: The cancer cells are limited to the epithelium, with an intact basement membrane and no stromal invasion. The pathological features are: ① Disordered cell arrangement, without polarity; ② Large cell nuclei with increased nuclear-cytoplasmic ratio; ③ Large nuclear atypia with uneven staining depth; ④ Abnormal mitotic figures are common, and can be found in all layers of the epithelium.

　　(2) Different types of cell types are formed according to the site of occurrence: ① Large cell keratinizing type; ② Large cell non-keratinizing type; ③ Small cell type. In situ carcinoma involving glands is very common and still has the characteristics of intact basement membrane and no stromal invasion. In situ carcinoma involving glands refers to the atypical hyperplastic squamous epithelial cells extending to the basal side, involving the glandular neck in the cervical canal mucosa, with clear tumor boundaries, no inflammatory reaction in the surrounding stroma, and visible residual tall columnar glandular epithelium. If the involved glands are significantly enlarged, deformed, or fused with each other, and the cell differentiation is poor, infiltration is likely to occur, which should be paid attention to and distinguished from microscopic infiltration.

　　(3) The pathological features of in situ adenocarcinoma described by Friedll and Mckay are:

　　① It often occurs near the transition zone of the lower segment of the cervix.

　　② It can also be limited to a cervical canal mucosal polyp.

　　③ It can involve a group of glandular structures or a single gland, growing into the stroma in bud-like manner, causing the glands to become sieve-like, and the papillae composed of epithelial cells can also penetrate into the glands or protrude on the surface of the cervix, but it is not invasive.

　　④ In situ adenocarcinoma is composed of pseudostratified columnar epithelium.

　　4, CIN Grading

　　(1) CIN is also divided into three grades according to the degree of atypicality of the cells:

　　① CINⅠ grade: Equivalent to very mild and mild atypical hyperplasia.

　　② CINⅡ grade: Equivalent to moderate atypical hyperplasia.

　　③ CINⅢ grade: Equivalent to severe atypical hyperplasia and in situ carcinoma.

　　(2) Recently, some authors have proposed that CIN cells can be divided into three subtypes according to their degree of maturation: ① Keratinizing type; ② Non-keratinizing type; ③ Small cell type. It is believed that this classification will provide a more comprehensive morphological basis for the correlation between histopathology and cytopathology, and is related to the hypothetical pathways of carcinogenesis of cervical cancer.

　　CINⅠ: Epithelial maturation, few nuclear abnormalities, and few mitotic figures, as shown in Figure 1. Undifferentiated cells are limited to the deep layer of the epithelium (lower 1/3). Mitotic figures can be seen, but not many, and the cytological changes of HPV infection can be observed throughout the full layer of the epithelium.

　　CINⅡ: The changes of atypical hyperplasia are mainly in the lower 1/2 or 1/3 of the epithelium, with more obvious nuclear abnormalities than CINⅠ, as shown in Figure 2. Mitotic figures can be seen in the lower 1/2 of the subepithelium.

　　CINⅢ: Epithelial differentiation and stratification may be lacking or only appear in 1/4 of the epithelial surface, accompanied by many mitotic figures, nuclear abnormalities may be present throughout the epithelium, and many mitotic figures are abnormal.

　　Intercommunication among cytologists, pathologists, and colposcopists can improve the reporting standards of three levels of CIN. It is especially helpful in distinguishing mild CIN.

　　Complications of cervical intraepithelial neoplasia: atypical hyperplasia in situ carcinoma often coexists with invasive carcinoma.

　　In situ carcinoma, also known as Bowen's disease, or intraepithelial carcinoma. It is more common in the elderly, often occurring at the junction of the cornea and conjunctiva, with clear boundaries between the tumor and adjacent normal tissue. It develops slowly, can be limited to the epithelium for several years, and pathological examination shows irregular epithelial hyperplasia, belonging to true intraepithelial carcinoma. The slices show disordered polarity of epithelial cells, with normal epithelial cells replaced by many atypical or multinucleated abnormal cells, common keratinization and incomplete morphological division phases, complete epithelial basement membrane, and generally good prognosis.

　　Invasive cervical cancer is often found during gynecological examination and confirmed by pathological biopsy and histological examination. Some cervical cancers are asymptomatic and have no visible abnormalities, and are called preclinical invasive cervical cancer.

　　CIN generally has no obvious symptoms and signs, and some may have increased leukorrhea, leukorrhea with blood, contact bleeding, and manifestations of chronic cervicitis such as cervical hypertrophy, congestion, erosion, polyps, etc., and the normal cervix also accounts for a considerable proportion (10% to 50%). Therefore, it is impossible to diagnose CIN solely by naked eye observation. Most literature reports that about half of in situ cancer patients have no clinical symptoms. Shuyi Jing (1995) statistically analyzed 172 cases of in situ cancer, of which only 5.2% had contact bleeding, 12.2% had small amounts of irregular bleeding, and the rest were asymptomatic. Li Nan et al. (2001) statistically analyzed 150 cases of CIN, among whom 26.0% had increased leukorrhea and 20.7% had contact bleeding, and 38.0% were asymptomatic.

　　In the past 20 years, the introduction of advanced methods such as thin-layer liquid-based cytology, cervical cytology Bethesda (TBS) reporting system, and hybrid capture (HCII) testing for human papillomavirus (HPV) has greatly improved the diagnostic level of cervical intraepithelial neoplasia. In terms of diagnosis, a basic point is to follow the 'three-step' model, that is, to carry out diagnosis according to the order of cervical cytology screening and HPV detection (if necessary) - colposcopy - cervical biopsy/cervical canal curettage (ECC). In treatment, the principle of individualization should also be followed. The treatment of cervical intraepithelial neoplasia includes observation and follow-up, cryotherapy, laser therapy, electrocoagulation, loop electrosurgical excision procedure, cervical conization, hysterectomy, as well as drug and photodynamic therapy, etc. How to standardize and reasonably select treatment is a common and very important clinical issue. The choice of treatment method should be comprehensively considered based on factors such as the grade of the lesion, the extent of the lesion, the patient's age, marital and childbearing status, follow-up conditions, and technical equipment. Regardless of the method of treatment, strict follow-up of the patient must be carried out.

　　Prognosis:

　　Richart pointed out that the higher the atypical degree of CIN and the deeper the involvement of the epidermal thickness, the greater the possibility of developing invasive cancer. Conversely, lower-grade CIN has more opportunities to revert to normal. CIN has three outcomes: ① regression (or reversal); ② persistence (or disease stability); ③ progression (or carcinogenesis).

　　1. Factors related to CIN progression

　　1. HPV types:Studies have suggested that HPV types are related factors in the progression of CIN (Richart et al., 1987). The risk of developing cervical cancer due to persistent high-risk HPV infection increases 250 times. Campion et al. (1986) followed up 100 cases of CINⅠ for more than 2 years, and among those with positive high-risk HPV16, 18 types, 56% progressed to CINⅢ, while only 20% of those with positive low-risk HPV6 types had progression.

　　2. The degree of CIN:With the increase of CIN grade, the probability of developing invasive carcinoma increases. Generally, 15% of CIN can develop into cervical cancer, among which the risk of developing cancer for CIN Ⅰ, Ⅱ, and Ⅲ grades is 15%, 30%, and 45%, respectively, as shown in Table 7. Mill et al. (1992) reported that the risk of progression from CIN Ⅰ, Ⅱ, and Ⅲ grades to invasive carcinoma was 4, 14.5, and 46.5 times higher than that of normal women.

　　3. Age:With the increase of age, the reversal rate of CIN lesions decreases. Mill et al. found that the overall reversal rate of CIN patients aged 35 to 39 was 77%, while for those over 40, it was 61%.

　　4. Other:such as intervention treatment for CIN, follow-up time, etc.

　　Second, regarding the outcome of SPI:Most scholars believe that SPI has similar clinical and biological characteristics to CIN. Although there are controversies about the outcome of SPI, several reports since the 1980s suggest that HPV also has three outcomes, which are related to the type of HPV. Rome and Chanan et al. (1987) reported on 259 cases of untreated SPI, followed up for 18 months, of which 16% had progression, 39% remained unchanged, and 45% regressed. Syrjanen et al. (1987) reported that among 513 cases of cervical cytology diagnosed with HPV type Ⅰ, 25% progressed to CIN, 60% remained unchanged, and 14% regressed.

　　Third, the outcome of cervical in situ carcinoma:Most believe that in situ carcinoma can progress to invasive carcinoma, while only a few naturally regress or disappear after biopsy. Some authors also believe that in situ carcinoma will not regress naturally. Mcindoe et al. (1984) reported on 300 cases of untreated in situ carcinoma, followed up for 10 to 20 years, with progression rates to invasive carcinoma of 18% and 36%, respectively. Yang Xuechang et al. (1992) observed 69 patients with in situ carcinoma who refused treatment, among whom 26% developed invasive carcinoma within an average of 5.2 years.

　　First, cytological examination:

　　Since Papanicloaou and Traut established the method of using vaginal exfoliated cytology for diagnosis in 1941, long-term clinical practice has proven that this method is simple, easy to perform, economical and effective, and can be repeated multiple times. It has become an important part of gynecological routine examination and the first choice for primary screening in cervical cancer screening. From a clinical perspective, the following points are worth paying attention to:

　　1. The accuracy of diagnosis:The positive diagnostic rate of cytology is as high as 95.4%, but the accuracy reported by different authors varies greatly (67% to 92.6%), and there is a certain degree of false-negative and false-positive results. The false-negative rate for detecting CIN is 10% to 35%, and even up to 50% (Coppleson, 1992). The accuracy of cytological diagnosis mainly depends on the following factors:

　　(1) Sampling site: It is the key factor affecting the quality of the smear. The routine sampling is at the squamous-columnar junction of the cervical external os, but because a certain proportion of cervical cancers originate from the cervical canal, especially adenocarcinoma and women before and after menopause, or women with local cervical treatment, the squamous-columnar junction may move upwards. Therefore, attention should be paid to the sampling of the cervical canal. Currently, it is advocated to use double smear method (i.e., simultaneous sampling of cervical and cervical canal smears) and repeated smears, which help to improve the quality of the smears and the positive rate. Some scholars reported that random use of cervical 'double sampler' and small foot plate sampling, and the comparison results showed that the detection rate of abnormal cells had a significant difference, respectively, 85.7% and 42.8%. The 'double sampler' has the advantages of easy use and one-time completion of double smears, but it is difficult to sample the cervical canal when the cervix atrophies. Shanghai has adopted the small spear-type scraper, which is considered suitable for elderly patients. Some studies have found that more than 80% of cells are discarded with the sampling device in routine smears, indicating that the cytological sampling tools still need to be improved.

　　(2) Strengthen quality control, improve the quality of preparation, staining technology, and diagnostic level: Poor smear quality affects the accuracy of diagnosis, accounting for 40%. Liquid-based cytology almost retains all the specimens on the sampling device, and the thin-layer smears produced improve the quality of the smears, making it easier to observe and read.

　　2. Unify diagnostic criteria and use new reporting methods (TBS):For a long time, most foreign countries have adopted the traditional Papanicolaou five-grade classification method. With the progress of cytopathology, it has gradually been felt that the Papanicolaou grading method can no longer meet the diagnostic and clinical requirements of the disease. In 1988, WHO proposed to use descriptive reports and a reporting system consistent with CIN, and the same year, the National Cancer Institute of the United States proposed the Bethesda system TBS reporting method, which is gradually improving in clinical practice.

　　3. Diagnosis of cervical warts:It was gradually recognized in the late 1970s. Meisels (1981) proposed that atypical warts are precancerous lesions. The positive rate of cytological detection of warts is low, with a detection rate of 3% to 4% in general surveys. Meisels (1992) reported that warts accounted for 3.23% in general surveys, and atypical warts accounted for 0.57%. The cytological morphology of warts is similar to that of CIN, and the vacuolated cells are easily mistaken for cancer cells. Atypical warts are often misdiagnosed as invasive squamous cell carcinoma and should be paid attention to. Attention should be paid to identification. The cytological characteristics of warts are as follows:

　　(1) Perinuclear vacuolated cells or挖空 cells.

　　(2) Dyskeratotic cells.

　　(3) Warts external basal cells.

　　4. Pay attention to the cytological diagnosis of cervical adenocarcinoma:Most people believe that cervical adenocarcinoma is not easily detected or diagnosed early, and it is often unexpectedly found during histological examination after cytological prediction of CIN. The positive rate of cytological diagnosis of adenocarcinoma is low, around 48%, and in recent years, the positive predictive value of cytology has been reported to be between 71% and 79% (Laverty, 1988). Routine scraping of the cervical external os and cervical canal smears may improve the detection rate of adenocarcinoma.

　　II. Observation of acetic acid application with the naked eye (VIA)

　　VIA refers to the direct observation of the degree of reaction of the cervical epithelium to 3% to 5% acetic acid solution under non-magnification conditions with the naked eye. The judgment is made according to the thickness, boundary contour, and rate of disappearance of the acetic acid white epithelium. This method has been used for cervical cancer screening in developing countries and economically backward regions since the 1990s. Belinson et al. (2001) reported that the sensitivity and specificity of VIA in cervical cancer screening were 70.9% and 74.3%, respectively. This method is simple, easy to perform, and economically effective.

　　III. Iodine solution test

　　Also known as the Schiller test, it involves applying iodine solution to the cervix and observing the stained areas. The normal cervical squamous epithelium contains glycogen, which, when mixed with iodine, produces a deep chestnut brown or deep brown color. Non-staining is positive. The squamous epithelium of cervicitis, precancerous lesions, and cervical cancer lacks glycogen or does not contain glycogen, and does not stain after applying iodine, which helps to locate the abnormal epithelium, identify dangerous lesions, and determine the site of tissue sampling for examination.

　　After determining the abnormal site of the cervix, the peripheral and distal boundaries should be determined. Through the application of the above solutions, the lower pole of the lesion can usually be identified under colposcopy, but occasionally the lesion can extend to the vaginal fornix. The upper edge of the lesion can be observed at the squamous-columnar junction using colposcopy.

　　IV. Colposcopy and biopsy under colposcopic guidance

　　1. Colposcopy:Colposcopy is a simple and effective method for diagnosing whether there are lesions in the cervix. Abnormal epithelium and abnormal capillaries that cannot be seen with the naked eye can be clearly seen through colposcopy. The characteristics of abnormal epithelium under colposcopy include:

　　(1) Increased cell and nuclear density.

　　(2) The contour of the squamous epithelium is irregular, accompanied by special vascular changes, which appear as punctation or mosaic. The former is due to the distortion or bending of capillaries within the epithelium reaching the surface obliquely, and the latter is due to the expansion of vessels, arranged in a honeycomb pattern, with the inner epithelial islands separated.

　　(3) White epithelium is the first feature of CIN, with a thick layer of keratin protein on the surface of the epithelium.

　　Colposcopy can further help identify the site of the lesion, thereby guiding the correct biopsy of the cervical site, but it cannot distinguish between in situ cancer and atypical hyperplasia. The accuracy of the colposcopic examination is related to whether the transitional zone is fully observed.

　　2. Cervical biopsy under colposcopic guidance:Cervical biopsy is the most reliable method for diagnosing CIN. The best method for confirming the diagnosis of CIN is to perform multiple biopsies at suspicious sites under colposcopic guidance. The biopsy tissue removed should have sufficient depth, including squamous epithelium and an adequate amount of stromal tissue, and it is best to obtain the surrounding tissue as well.

　　V. Cervical biopsy and cervical canal scraping

　　The diagnosis of CIN and cervical cancer must be based on the pathological examination of cervical living tissue.

　　1, When performing cervical biopsy, the following points should be noted:

　　(1) Multiple biopsies should be performed at multiple points under iodine staining, VIA, or colposcopy, and marked for pathological examination separately;

　　(2) Sampling includes the lesion and surrounding tissue;

　　(3) Bite the cervical epithelium and sufficient stroma tissue;

　　(4) Repeat biopsy or incisional biopsy should be performed when clinical or cytological suspicion is present.

　　2, Cervical canal scraping (ECC):Scrape the endometrial tissue of the cervical canal for pathological examination, which helps to clarify whether there are lesions in the cervical canal and whether CIN or cancer has involved the cervical canal. However, whether it should be a routine examination is currently not consistent. Indications for cervical canal scraping include:

　　(1) Abnormal cytology or clinical suspicion in perimenopausal women, especially when adenocarcinoma is suspected;

　　(2) Lesions involving the cervical canal under colposcopy;

　　(3) Multiple positive or suspicious cytology, negative or unsatisfactory colposcopy, or negative biopsy under colposcopy.

　　Sixth, cervical cone resection

　　It is a traditional and reliable diagnostic method for cervical cancer, due to the widespread use of colposcopy, the rate of diagnostic conization has decreased significantly. In the 1990s, several groups of foreign reports compared the role of colposcopic biopsy and cone biopsy in the diagnosis of CIN and invasive cancer, with similar results. Indications for diagnostic conization include:

　　1, Multiple positive cytological tests, normal colposcopic examination or unable to see the entire transformation zone, or negative biopsy under colposcopy and ECC.

　　2, Cytological report does not match the result of biopsy under colposcopy or cervical canal scraping.

　　3, Vaginal application with acetic acid (VIA) or biopsy under colposcopy suggesting early invasion.

　　4, CIN lesions with higher grade extending into the cervical canal.

　　5, Suspected adenocarcinoma, clinical or colposcopic examination showing suspicious invasive cancer is a contraindication for surgery.

　　Since the 1990s, the loop electrosurgical excision procedure (LEEP) and large loop excision of the transformation zone (LLETZ) of the cervix have been widely used in the diagnosis and treatment of CIN, so they also have both diagnostic and therapeutic effects.

　　First, dietary therapy for cervical intraepithelial neoplasia

　　1, Astragalus 12 grams, Angelica sinensis 15 grams, Codonopsis pilosula 9 grams, Atractylodes macrocephala 9 grams, Asparagus cochinchinensis 9 grams, Poria 9 grams, Dioscorea opposita 9 grams, Radix paeoniae alba 6 grams, Ligusticum chuanxiong 6 grams, Glycyrrhiza uralensis 5 grams. Decoct and take one dose a day. Mainly for patients with cervical cancer due to deficiency of Qi.

　　2, Smilax glabra 30 grams, Taraxacum mongolicum 30 grams, Poria 25 grams, Inula japonica 25 grams, Atractylodes macrocephala 15 grams, Angelica sinensis 9 grams, Radix paeoniae alba 9 grams, Bupleurum chinense 4.5 grams, Alisma orientale 9 grams. Decoct and take one dose a day. Coix lacryma-jobi 60 grams, Cnidium monnieri 30 grams, Dendranthema indicum 30 grams, Lonicera japonica 30 grams, Angelica dahurica 15 grams, Acorus calamus 15 grams. Boil with appropriate amount of water.

　　3, Arisaema 30 grams (boiled for 2 hours first), Poria 24 grams, Lobelia chinensis 30 grams, Hedyotis diffusa 30 grams, Fraxinus chinensis 12 grams, Atractylodes macrocephala 24 grams, Curcuma 15 grams, Angelica sinensis 12 grams, Cyperus rotundus 12 grams, Moutan Cortex 12 grams, Citrus reticulata 12 grams. Decoct and take one dose a day.

　　4, Scorpion 10 grams, Beehive 10 grams, Snake skin 10 grams. First, soak the scorpion in cold water for 24 hours (change the water 2-3 times), then dry it in the sun and toast it slightly with low heat, and slightly fry the beehive and snake skin separately. Grind into powder, make into pills with water, 2 grams each time, twice a day.

　　5, Lamb 300 grams, fresh river fish 1 piece (500 grams), white radish 1 piece. Cut the lamb into large pieces, put it in boiling water, boil with sliced radish for 15 minutes, discard the soup and radish. Put the lamb in the pot, add water (about 2/3 of the pot capacity), scallion, ginger, wine, and boil until tender. If the soup is too little, add an appropriate amount of boiling water. Fry the fish with soybean oil until golden, then put it in the lamb pot and boil for 30 minutes. Add salt, coriander, green onion, and chopped scallion to the soup, and it becomes a delicious and delicious lamb and fish soup. Mainly used for postoperative recuperation after cervical cancer surgery.

　　6, Sangjisheng 30 grams, Huangjing 15 grams, Taizishen 15 grams, Xuduan 15 grams, Yiren 12 grams, Baizhu 9 grams, Gouji 9 grams, Chenpi 9 grams, Shengma 3 grams. Decocted in water, one dose per day. Mainly used for obvious sinking of the middle Qi in the cervix.

　　7, Baihuasheshecao 30 grams, Banjigong 15 grams, Huai Shan 15 grams, Caoheshua 15 grams, Shengdi 12 grams, Zhimu 9 grams, Zexie 9 grams, Hanliancao 15 grams, Xuanshen 9 grams, Huangbai 4.5 grams. Decocted in water, one dose per day.

　　8, Lingfen Congee: Boil 100 grams of sticky rice with an appropriate amount of water, add 30-60 grams of lingfen when the congee is half-cooked, add a little brown sugar, and cook into congee. Eating congee made with lingzhi powder not only invigorates the spleen and stomach but can also be used as an auxiliary dietary prevention and treatment measure for esophageal cancer, gastric cancer, breast cancer, and cervical cancer.

　　9, Tufuling 50 grams, sugar (or honey) as needed. Add two and a half bowls of water to Tufuling, simmer over low heat until one bowl, add sugar or honey for taste when using. Mainly used for increased leukorrhea in cervical cancer.

　　10, Renshen 18 grams, Biejia 18 grams, Huajiao 9 grams. Grind into fine powder, take 7 grams each time, once a day, mixed with warm water for administration, 24 days as one course.

　　11, Honghua 6 grams, Baifan 6 grams, Wapu 30 grams. Decocted, first fumigate, then wash the external genitalia, once or twice a day, 30-60 minutes each time, reheat before using, one dose can be used for three to four days. Mainly used for early cervical cancer.

　　12, Kunchong 3 grams, Hai藻 3 grams, Xiangfu 5 grams, Baizhu 5 grams, Fuling 5 grams, Danggui 6 grams, Baishao 10 grams, Chaihu 3 grams, Quanxie 3 grams, Wugong 2 pieces. Decocted in water, three doses per week. Mainly used for early cervical cancer.

　　13, Quail eggs 20 pieces, half an onion, carrot 80 grams, asparagus 80 grams, bell pepper 4 pieces, green pepper 1 piece. Boil the eggs and use the shells. Cut the vegetables into small pieces. Boil the carrots until just cooked. Put 200 milliliters of soup ingredients, 40 grams of sugar, 45 milliliters of vinegar, 15 milliliters of wine, 20 grams of tomato sauce, 5 milliliters of sesame oil, 10 grams of Jeifen, and mix into a sauce. Heat 30 milliliters of oil in a pot, stir-fry the eggs and vegetables for a second, then pour in the sauce and cook for a while before serving. Mainly used for anemia caused by chronic bleeding in cervical cancer.

　　14, Xianfucao 30 grams, Shandougen 30 grams, Pollen 15 grams, Qiye Yizhihua 30 grams, Qiancao 15 grams, Chaihu 15 grams, Yimu 9 grams, Sanleng 9 grams. Decocted in water, one dose per day. Mainly used for cauliflower type and ulcerative cervical cancer.

　　15, 15 grams of angelica sinensis, 15 grams of bupleurum chinense, 15 grams of chicken gizzards, 30 grams of codonopsis pilosula, 9 grams of atractylodes macrocephala, 9 grams of white peony root, 9 grams of poria cocos, 9 grams of citrus reticulata, 9 grams of lindera aggregata, 7 grams of glycyrrhiza uralensis. Decoct and take one dose per day. It is used to treat cauliflower-type and erosive-type cervical cancer.

　　16, 30 grams of cantharidin, 30 grams of plantago asiatica, 30 grams of talc, 30 grams of clematis. Grind into fine powder, make into pills with water, take 0.1-0.12 grams per dose, once a day.

　　17, 30 grams of houttuynia, 30 grams of white mugwort root, 15 grams of salvia miltiorrhiza, 9 grams of angelica sinensis, 30 grams of oyster, 60 grams of hedyotis diffusa, 9 grams of salvia miltiorrhiza, 15 grams of codonopsis pilosula, 9 grams of atractylodes macrocephala, 9 grams of white peony root, 9 grams of rhizoma alismatis, and 9 grams of radix tieguainen. Decoct and take one dose per day.

　　18, 1 pigeon, an unlimited amount of vinegar, 30 grams of turtle shell, 30 grams of Chinese yam. After the pigeon is slaughtered, remove the internal organs and chop them. Boil with the latter two ingredients in water until tender, season with salt, and drink the soup and eat the meat. It is applicable to other gynecological tumors in addition to cervical cancer.

　　19, 1 eel, 60 grams of fresh vervain (30 grams of dried). Remove the internal organs of the eel and boil with vervain (wrapped in cloth) in an appropriate amount of water for one hour. Remove the medicine, season with salt and oil, and drink the soup and eat the fish. It is used to treat cervical cancer with irregular menstruation and red and white leukorrhea.

　　20, 250 grams of black-bone chicken, 30 grams of sea cucumber, 30 grams of scallion whites. First, cut the chicken into pieces and cook with sea cucumber in a pot with an appropriate amount of water. Cook until the chicken is tender, add scallion whites, salt, and oil, and boil for 15 minutes. Drink the soup and eat the meat. It is used to treat cervical leukorrhea with red and white, foul-smelling discharge and vaginal cancer.

　　21, 1 chicken, 12 grams of mugwort绒, 15 grams of Chinese wolfberry. Kill the chicken according to common methods and remove the internal organs. Put the mugwort (wrapped in cloth) and Chinese wolfberry into the chicken's abdomen, seal with bamboo skewers, and simmer in water until tender. Remove the mugwort, season with salt, and drink the soup and eat the meat. It is used to treat cervical cancer with weakness.

　　22, 60 grams of lean pork, 30 grams of fish glue, 60 grams of glutinous rice. Cut the pork and fish glue (soaked for one day) into strips, cook with rice, and season with salt and oil for consumption. It is used to treat cervical and ovarian cancer with weakness and lack of appetite.

　　23, 25 grams of mugwort leaves, 2 eggs. Boil mugwort leaves and eggs in an earthen pot (avoid using iron utensils) over low heat. After the eggs are cooked, remove the shell and boil for another 10 minutes. It is used to treat chronic cold pain in the lower abdomen of cervical cancer.

　　Secondly, what should cervical intraepithelial neoplasia patients eat to benefit their health

　　1, Early cervical cancer (uterine cervical cancer) generally has little impact on digestive function. The main focus should be on enhancing the patient's ability to resist disease and improving the immune function. Nutrients such as protein, sugar, fat, and vitamins should be consumed reasonably. When the patient has excessive vaginal bleeding, foods that help with blood replenishment, hemostasis, and anti-cancer effects should be taken, such as lotus root, Job's tears, hawthorn, black fungus, and umeboshi. When the patient has excessive, watery leukorrhea, it is advisable to take nourishing foods, such as turtle, pigeon eggs, and chicken. When the patient has excessive, sticky leukorrhea with an unpleasant smell, it is advisable to eat light and diuretic foods, such as Job's tears, red bean, and white mugwort root.

　　2, After surgery, diet adjustment should focus on nourishing Qi and blood, and boosting the essence with foods such as yam, longan, mulberry, goji, pork liver, turtle, sesame, and donkey hide glue.

　　3. Vitamin malnutrition. Some people have observed that the level of B-carotene in the blood of cervical cancer patients is lower than that in the control group, and low intake of B-carotene is a risk factor for cervical cancer. In addition, vitamin C is also related to the incidence of cervical cancer. Chinese investigations show that when the intake of vitamin C increases, the risk of cervical cancer decreases.

　　4. Trace elements. It has now been found that copper, zinc, and selenium are related to trace elements. The Cancer Prevention and Treatment Institute of Guizhou Province found that there were significant differences in cervical cancer and breast cancer, and the plasma copper in the recent and long-term recurrence group was significantly higher than that in the non-recurrence long-term survival group and normal people. The plasma copper in the long-term recurrence group was significantly higher than that in the non-recurrence group. The copper ratio was the highest in the long-term recurrence group. The copper-zinc ratio in the current group was also significantly higher than that in the normal and non-recurrence groups. Plasma copper and copper-zinc ratio can be used as indicators for the diagnosis of cervical cancer and malignant tumors and prognosis. Some people have investigated that the incidence of cervical cancer is related to high copper intake, which may be due to the antagonistic effect of copper on selenium, and high doses of copper can produce selenium deficiency symptoms in animals. Therefore, attention should be paid to supplementing vitamins in daily diet, and appropriate attention should be paid to supplementing foods containing zinc and selenium.

　　Third, what should cervical intraepithelial neoplasia patients avoid eating for their health

　　1. Cervical cancer is caused by blood and Qi stasis, phlegm and dampness aggregation, and toxic heat accumulation. Diet should avoid fatty, sweet, spicy, smelly, and oily fried and roasted foods that produce dampness, phlegm, and dry heat, which are easy to cause bleeding.

　　2. When patients have a lot of watery leukorrhea, they should avoid eating cold and raw foods, fruits, cold foods, and hard-to-digest foods; when leukorrhea is sticky and has an unpleasant smell, they should avoid eating greasy and sticky foods.

　　First, treatment

　　1. Treatment Principles

　　The treatment strategy for CIN in modern times tends to be conservative, for the following reasons:

　　The comprehensive diagnostic level of CIN and early cancer has improved;

　　The occurrence and development of cervical cancer take a relatively long time, about 10 years;

　　20% to 50% of atypical hyperplasia can be reversed or spontaneously regressed;

　　The vast majority of CIN lesions are localized, and the one-time cure rate of conservative treatment is as high as about 90%;

　　The 5-year survival rate of in situ carcinoma is 100%, but to this day, there are many controversies about the treatment of CIN in China and abroad.

　　(1) There is no consensus on whether to treat CINⅠ or cervical SPI. Studies on the natural course of CIN suggest that low-grade CIN has a high rate of spontaneous regression, most of which are related to low-risk HPV infection, with an extremely rare chance of progressing to cancer. In recent years, it is considered that CINⅠ is an unstable state, and these earliest precancerous lesions should be observed without treatment (Jordan, 1989; Shuyi Jing, 1995). Conversely, many authors believe that all CIN patients should be treated, regardless of their relationship with the virus and typing, mainly from the perspective of cervical cancer prevention and treatment, a positive attitude should be held and appropriate precancerous blocking treatment should be given.

　　Syrjaen (1987) advocated that the treatment of SPI should be the same as that of CIN. The Cancer Hospital of the Medical Academy, combining literature and its own experience, believes that conservative treatment can be adopted for the following situations:

　　Cervical condyloma with CIN;

　　CINⅠ associated with high-risk HPV (16, 18, 31, 33, 45...);

　　③ For those with a large extent of the lesion, without follow-up conditions, or those who are mentally tense and refuse to be observed, it must be pointed out that excessive aggressive treatment plans should not be adopted.

　　(2) There is a significant difference in the conservative treatment of CINⅢ: The failure rate of conservative treatment is reported to be high in foreign literature. Ostergard (1980) reported that the failure rate of cryotherapy for CINⅢ was up to 39.0%, and Benedet et al. (1981) reported the occurrence of invasive cancer after cryotherapy, so it is considered that CINⅢ is not suitable for cryotherapy. Another author studied 343 cases of CINⅢ conization specimens, and 99.7% of the glands were involved in the depth

　　However, considering the following reasons:

　　① The opportunity for CINⅢ to progress to cancer is significantly increased, with more than 65% of severe atypical hyperplasia developing into in situ cancer, and 18% to 36% of in situ cancers progressing to invasive cancer.

　　② CINⅢ often coexists with early invasive or invasive cancer, and differences in diagnostic levels may lead to insufficient diagnosis and missed diagnosis.

　　③ Patients with CINⅢ who have received conservative treatment need close follow-up, while most patients in China come from rural areas and lack long-term follow-up conditions.

　　Therefore, for those with CINⅢ who have no fertility requirements, total hysterectomy is the best treatment choice.

　　(3) Cervical conization is used for the treatment of in situ cancer, and there are still different opinions about it. It is widely used abroad, but most of the literature reports that the recurrence rate after conization is higher than that after total hysterectomy. Demopoulos et al. (1991) reported that 96 cases of CINⅢ were treated with cervical conization, with a positive margin rate of 39.6%. The hysterectomy was performed 8 weeks after the operation, and 38.5% had residual lesions. Parson (1978) reported that the residual or recurrent cancer after conization was 3.2% to 9.1%. Coppleson et al. (1992) collected data from 13 authors, and the residual lesion rate after the operation was 12% to 60%. Chang studied the pathological specimens of 172 cases of hysterectomy after cervical conization and found that the incidence of positive margins and residual lesions in high-grade squamous intraepithelial lesions (HSIL, including Ⅱ and Ⅲ) were 18.6% and 23.3%, respectively. The proportion of residual lesions in positive margins was significantly higher than that in negative margins, respectively, 84.8% and 10.1%. It can be seen that the treatment of in situ cancer with conization is not thorough and there is a possibility of missing invasive cancer. In recent years, there have also been many reports that traditional conization (CKC) has successfully treated in situ cervical cancer (Mohamed et al., 1997).

　　In summary, the treatment of CIN should also follow the principle of individualization. The choice of treatment method mainly depends on the level of CIN, the extent of the lesion, age, fertility requirements, medical conditions, and the experience of the physician. The general treatment strategy is: for CINⅠ and Ⅱ, local treatments such as cryotherapy and laser therapy are adopted; for CINⅢ, in China, the main treatment is the surgical removal of the uterus, while some foreign countries advocate local treatment. For young patients with CINⅠ who have fertility requirements and a small extent of the lesion, follow-up observation can be performed, while for those with localized lesions, young age, fertility requirements, or the desire to preserve the uterus, conization can be performed.

　　The effectiveness of local treatment for CIN is mainly related to the following factors: ① CIN level, size of the lesion; ② Treatment depth; ③ Whether the entire transformation zone is removed; ④ Coexisting recurrent or persistent HPV infection (especially high-risk HPV); ⑤ Whether the cervical canal is involved; ⑥ Cure standards, follow-up time, physician experience, etc.

　　Therefore, the following points should be paid attention to when local treatment is adopted:

　　① A detailed examination must be conducted before treatment, an accurate diagnosis must be made, and invasive cancer must be excluded;

　　② ECC examination should be performed before treatment;

　　③ Perform the treatment 5-7 days after the menstrual period is clean;

　　④ Treatment should be performed under the direct vision of iodine staining, VIA, or colposcopy;

　　⑤ The treatment should reach a sufficient depth, not less than 4mm, and the treatment range should include the entire lesion of the cervix (it is better to exceed the lesion by 3-5mm), the whole transformation zone, and the lower segment of the cervical canal;

　　⑥ Long-term follow-up after treatment should include cytology, colposcopy, and pathology.

　　2. Common treatment methods for CIN

　　(1) Cryosurgery: There are many literature reports on cryotherapy for CIN. The cure rate of CINⅠ and Ⅱ can reach 90% to 97%, while the treatment effect of CINⅢ is poorer, 80% to 90%, but there are also reports that it can reach 96% (Levine, 1985). Coppleson et al. (1992) statistically analyzed the treatment results of 15 authors, with a total cure rate of 83.5%, among which the cure rates of CINⅡ and Ⅲ are 91% and 77.8%, respectively, indicating that the cure rate decreases significantly with the increase of CIN levels.

　　Cryotherapy is simple and effective, and the biggest advantage of cryotherapy is that it does not cause pain like electric cauterization. The depth of treatment is the same as electric cauterization, which can reach 3-4mm, but some patients may still feel uncomfortable due to the need for repeated treatment, especially when deep treatment is performed, which may be the result of uterine contraction. Richard and other researchers, as well as the most reported 16 authors, believe that cryotherapy for all CIN has a failure rate of 1% to 8%, with CINⅠ having a zero failure rate. It is noteworthy that after failure, re-cryotherapy can reduce the failure rate of CINⅡ to 3% and the failure rate of CIN to 7%. The cryogen used in cryotherapy, carbon dioxide (carbondioxide) or nitrous oxide (nitrousoxide), results are the same. Only the pressure during treatment should not be as low as 40kg/cm2, and the part of the probe contacting the cervix, except for the middle part which is papillary, should be 4-5mm wide. At the same time, to ensure uniform and rapid freezing, it is more ideal to apply a thin layer of water-soluble lubricating oil to the probe part.

　　It is generally believed that cryotherapy is suitable for CINⅠ and Ⅱ with localized lesions. To improve the cure rate and reduce recurrence, the following points should be noted in cryotherapy:

　　① Select the appropriate cryoprobe according to the cervical morphology and the extent of the lesion. It is advisable to cover the entire lesion. A thin layer of water-soluble lubricant should be applied to the tip of the cryoprobe as a medium to improve its penetrability and increase uniform contact with the cervix, allowing for rapid temperature transfer.

　　② The cryogen is CO2 or liquid nitrogen, with a temperature below -75°C. Pressure is an important factor for the success of cryotherapy and must always be maintained above 3.92×10^6 Pa (40 kgf/cm^2) to ensure the cryogenic capacity. A cold ball with a thickness of 4-5mm should be formed around the probe within 1.5-2 minutes.

　　③ Apply treatment twice, i.e., two freezing and thawing cycles, to achieve better efficacy.

　　(2) Laser treatment: Bellina and Poleshchuk applied CO2 laser therapy for gynecological tumors in the 1970s, and foreign literature reported the effectiveness of laser treatment for CIN in the 1980s. Towensend (1983) compared the results of laser and cryotherapy for CIN (each with 100 cases), with failure rates of 11% and 7%, respectively. Coppleson summarized the literature and reported a cure rate of 76% to 98%. The Shanghai Medical University Hospital reported that 220 cases of CIN were treated with laser therapy, with a normalization rate of 65.5%, higher than other therapies, and a recurrence rate of 5.8%.

　　Laser treatment is generally performed under colposcopy, with the energy emitted by the laser released from a pinpoint beam and absorbed by the tissue. It can destroy the tissue and evaporate it, and the ablation medium of the laser is also carbon dioxide. Continuous treatment is more effective than intermittent treatment, with a depth of up to 5-7mm. However, flammable items such as alcohol and disinfectants should not be used during treatment. In addition, the smoke produced during treatment can be blown away with a straw to provide a clearer view. Apart from the benefits of deeper tissue destruction, laser treatment has at least two drawbacks: it is more painful than electrocautery and cryotherapy, which is an inevitable phenomenon after deep tissue destruction, and therefore results in more bleeding. According to the report by Parashevadis et al., the overall failure rate is 5.6% (119/2130), with the highest failure rate in patients over 40 years old and those with CINⅢ, reaching 75%, while the lowest failure rate is 7% in CINⅠ. Three patients were found to have invasive cancer after 2 years of laser treatment. In addition, Townsend and Richard reported that 100 patients were treated with laser therapy, and another 100 patients were treated with cryotherapy, with 11 and 7 failures, respectively, indicating no statistical difference. Therefore, their conclusion is that since the treatment outcomes of both methods are similar, they can be considered for outpatient treatment, which is convenient for patients, less painful, and cost-effective. The most painless and cost-saving method is cryotherapy and electrocautery.

　　Laser therapy has the advantages of simple operation, precise treatment, fast tissue healing, and few complications. In the 1990s, there were reports of using CO2 laser fibers to transmit laser, which is convenient to operate and can enter the cavity for treatment. Baggish et al. (1985) applied a comprehensive treatment of laser cutting and ablation for CIN, with a cure rate of 97%, which has little impact on childbirth. Some scholars have used laser conization to treat 473 cases of CIN, followed up for more than 5 years, with a cure rate of 96.6% and a recurrence rate of 3.4%. It is believed that laser conization is suitable for patients with positive cervical canal scraping, unsatisfactory colposcopy, large CIN area, over 35 years old, and those who refuse conservative treatment.

　　(3) Electrocoagulation diathermy: Many foreign reports have used electrocoagulation therapy for CIN. In the United States, Europe, and Australia, it was very common from the beginning and later spread to all corners of the world. The effectiveness of electrocoagulation therapy for CIN should be undoubtedly effective, as the depth of electrocautery can reach 3 to 4mm. There are almost no reports of failure in the treatment of CINⅠ and CINⅡ, but a small number of CINⅡ cases may have CINⅢ or even invasive cancer. Therefore, careful examination should be performed before treatment, including colposcopy and even biopsy, as well as dilation and curettage (D&C) of the cervix when necessary. For CINⅢ, the failure rate of treatment is about 13%, and there is no difference between the early-stage cancer with or without glandular invasion. Chanen and Rome reported the largest number of cases, reaching 1734, with only a 3% failure rate among all patients (CINⅠ to CINⅢ), all of whom were treated on an outpatient basis. Only a few patients require deep electrocautery to destroy deeper lesions including glands, which may require anesthesia and possibly hospitalization. As for the possible occurrence of cervical stenosis, it is actually very rare, but the possibility is higher after deep electrocautery. It is not advisable to perform cervical dilation and curettage at the same time as electrocautery, which can reduce the occurrence of this side effect. The advantages are that the treatment area is wider, the depth can reach 3 to 4mm, and the therapeutic effect can reach 90% to 95%. Chanen and Rome (1983) reported that 1864 cases of CIN were treated with electrocoagulation, of which two-thirds were CINⅢ, with a cure rate of 97% in a single treatment. However, electrocoagulation should not be too deep, otherwise it may cause pain and postoperative hemorrhage, so anesthesia is often required during treatment.

　　(4) Loop electrosurgical excision procedure (LEEP) or large-loop excision of the transformation zone (LLFTZ): LEEP was first proposed by the French scholar Cartier (1981) and is a new type of electroresection therapy. Since the 1990s, the use of LEEP for the treatment of CIN has been reported陆续 abroad. ALVarez et al. (1994), Messing et al. (1994) conducted a randomized study on the treatment of 110 cases of CIN110 with three methods: conization, laser, and LEEP. The results suggest that LEEP has the advantages of being fast, simple, inexpensive, with fewer complications, and convenient for outpatients. In recent years, more clinical studies have been conducted on the indications, excision range, and existing problems of LEEP. Combining literature and experience, it is considered that the following indications are more appropriate.

　　① Indications for LEEP surgery:

　　A. Indications for LEEP as a diagnostic method:

　　a. Cytology shows ASCUS or AGC, and colposcopic examination shows no obvious abnormalities.

　　b. Suspicion of HSIL based on cytology or colposcopic examination.

　　c. Unsatisfactory colposcopic examination and cytological abnormalities.

　　B. Indications for LEEP treatment:

　　a. Patients with persistent CINⅠ without follow-up conditions, or CINⅠ accompanied by high-risk HPV infection.

　　b. CIN II.

　　c. In CIN III with moderate to severe atypical hyperplasia, there are reports that the recurrence rate of LEEP treatment for cervical in situ adenocarcinoma is 29.0%, therefore, in situ carcinoma, especially in situ adenocarcinoma, is not suitable for LEEP treatment (Widrich et al., 1996).

　　② Scope and effectiveness of LEEP treatment: The cone resection range of LEEP should exceed 1mm beyond the cervical lesion, with a depth of 7mm and a cervical canal depth of about 15mm. If it is used for CIN I or ASC, the cervical depth and cervical canal depth can be 4mm each (Wan Meilu et al., 2000). The cure rate of LEEP treatment for CIN is 89.4% to 93.3%, and the incidence rate of complications is 2.7% to 14.1%, mainly postoperative hemorrhage.

　　③ Issues with LEEP: The application of this new treatment method, LEEP, has been relatively short, and there are many issues, such as whether LEEP can be used as a diagnostic method to exclude invasive cancer, whether it is suitable for the treatment of in situ carcinoma, whether thermal injury affects the pathological evaluation of the tissue at the edge of cone resection, insufficient or excessive treatment, etc. The literature reports are inconsistent, and further exploration is needed.

　　(5) Cervical cone resection: It is a traditional treatment method commonly used in China. It was widely used in the treatment of CIN in Europe. However, due to the high incidence of residual lesions and recurrence reported by many authors after cone resection, as well as certain complications, most scholars advocate that the indications for cone resection should be strictly controlled. It still has a certain status in the treatment of in situ carcinoma in young, childless patients. In addition, cone resection can also be adopted for CIN III patients with localized lesions, who refuse or cannot tolerate major surgery.

　　Cone resection is particularly suitable for severe CIN and CIS, which can both diagnose and treat. In cases of microscopic invasive cancer, even if there is only a little invasion, cone resection can also be considered. This operation is performed through the vagina, and if the removed cervical canal is viewed upside down, it presents a conical shape, hence the name cone resection or cone section. During the operation, the transformation zone of the cervix, where squamous epithelium and columnar epithelial cells intersect, must be visible. The specimen from endocervical curettage must not contain cancer cells. To do this job well, it is usually necessary to first expose the cervix, then use a cotton swab soaked in saline to clean the mucus on the surface of the cervix, and finally apply 4% acetic acid evenly on the cervix. The acetic acid condenses the protein produced by the lesion in the epithelial layer and appears white. The edge of the resected part must cover all the white areas, so the shape may not necessarily be round. The incision is based on the lesion, of course, more margin is needed, which means there should be no residual lesion at the edge. It is best to perform this operation under the guidance of a colposcope. However, if the general clinical physician has already had a good colposcopy examination result, the operation can use acetic acid to assist in the determination of the scope, cut off enough margin, which can reduce residual lesions and recurrence. When the edge of the cone resection specimen still contains cancer cells, a second resection is needed because there may be invasive cancer at the problematic edge. Our other suggestion is to do a smear first. If the smear results are normal, observation can be done first. Unless cervical stenosis affects the results of the smear, a second resection should be performed.

　　Since conization always requires a simultaneous cervical canal dilation and curettage operation, anesthetic drugs can be used, including general anesthesia and local anesthesia. Deep sedatives can be used for 15 to 20 minutes. There are many types of surgical blades used, such as electrocautery, general blades, and laser blades. There is almost no difference in hemostasis and pathological interpretation. For the relatively common bleeding problems, electrocautery indeed has a good hemostatic effect. Before the operation ends, if a hemostatic mesh (surgicel) or foam gel (gelfoam) is placed on the wound, the hemostatic effect is even better. Conversely, the hemostatic effect of the suture method (Sturmdorfsuture) that wraps the epithelium of the cervix from above and below inward and around is generally poor. Currently, these complications are not common. After conization, it may cause cervical stenosis and incomplete cervix (incompetent cervix), which is even rarer. As for CIN patients with difficult-to-read resection margins, if the smear is normal in the first year after surgery, the effect is good, and the probability of abnormal smears appearing later is only 0.4%. Kolstad et al. followed up 795 cases of in situ carcinoma (CIS) that underwent conization for 5 to 25 years and found that the recurrence rate of in situ carcinoma was only 2.3% (19/795), and invasive cancer was 0.9% (7/795). Bjerre et al. reported a recurrence rate of in situ carcinoma of only 0.6% and invasive cancer of 0.6%. According to the statistics of Taipei荣民General Hospital (1998), among 775 cases of in situ carcinoma followed up for more than 5 years, the recurrence rate of in situ carcinoma was 0.25% (2/775), and invasive cancer was 0.13% (1/775).

　　Loop electrosurgical excision procedure (LEEP) was popular in the 1990s and is another method of conization. After seeing the transformation zone of the cervix, a circular excision is made, generally with a depth of 5 to 8 mm, which also has diagnostic and therapeutic effects.

　　After the 1990s, the traditional cervical conization was referred to as cold knife conization (CKC) in literature. In today's emphasis on the quality of life, the update of concepts and the improvement of technology have led people to re-understand the value of cold knife conization in the diagnosis and treatment of CIN. Currently, the clinical application of CKC has increased, and it has become an important treatment method for CIN patients.

　　To reduce the recurrence after cone resection, the following points should be emphasized during cone resection:

　　① It is recommended to perform the operation under iodine staining, VIA, and/or colposcopy.

　　② The resection range includes abnormal lesions seen under colposcopy, the entire transformation zone, the entire squamocolumnar junction, and the lower part of the cervical canal. The resection width is 0.5 cm outside the lesion, and the depth is below the internal os of the cervical canal, generally about 2.0 cm.

　　③ The cone resection specimen must be examined in detail, especially the edges and the tip of the cone, to check for any residual lesions.

　　The main immediate complications after cone resection are bleeding (5% to 10%), and long-term complications include cervical canal stenosis, relaxation of the cervical internal os, leading to late abortion or preterm delivery, etc.

　　(6) Total hysterectomy: It is the most commonly used and thorough treatment method for cervical in situ cancer. For patients with precancerous lesions, especially CINⅡ and CINⅢ, who no longer want to give birth, or those with other uterine, ovarian, and fallopian tube diseases, such as benign tumors, total hysterectomy is usually performed; if there is a uterus prolapse, which was more common in the past, most likely a total hysterectomy will be performed through the vagina (vaginal hysterectomy). Regarding in situ cancer, Kolstad et al. reported that among 238 patients who underwent hysterectomy, the long-term follow-up results from 5 to 25 years: recurrence rate (in situ cancer) 1.2% (3/238), invasive cancer 2.1% (5/238). Compared with cone resection, although there are numerical differences, there is no statistical difference. It is almost the same as the view of Bjerre et al. (3729 people): the recurrence rate of in situ cancer after hysterectomy is 0.9%, and the invasive cancer is 0.3%.

　　As for surgery, in order to reduce recurrence, in the past, doctors would usually resect part of the upper vagina. After analyzing 861 patients, Creasman and Rutledge et al. emphasized that there is no need for this. They believe that the recurrence of cervical in situ cancer is not related to the amount of vaginal resection. The number of patients analyzed by each author is listed in the table for reference (Tables 4, 5, 6).

　　For patients with CINⅢ who have no fertility requirements or are middle-aged or elderly, total hysterectomy is also a preferred treatment method. However, there is still disagreement on whether to simultaneously remove part of the vagina. Greasman and Rutledge once found that the recurrence of in situ cancer is unrelated to the resection of the vaginal wall, advocating that there is no need to expand the operation. Parson et al. (1978) emphasized the removal of an appropriate amount of vaginal wall to minimize the risk of recurrence. However, people have noticed the issue of

　　(7) Radiotherapy: For patients with in situ adenocarcinoma who have surgical contraindications or refuse surgery, simple intracavitary radiotherapy can be used.

　　(8) Management of in situ adenocarcinoma and intraductal adenoma: Due to the limited understanding of the natural history of adenocarcinoma, there are few reports on the management of ACIS and CIGN. However, recent studies are worth attention. Poynor et al. (1995) reported that 40% of 28 ACIS cone biopsy specimens had residual lesions, 43% of those with negative cone biopsy margins recurred, with a total recurrence rate of 47%, of which 13.3% were invasive cancers, suggesting that ACIS has a multi-focal characteristic, often coexisting with invasive adenocarcinoma. Kenned et al. (1996) reported atypical glandular cells (AGUS) with no clear significance in cytological diagnosis, of which at least 4% had invasive cancer, 13% had precancerous lesions, and one case was found to have adenocarcinoma within 4 months. The authors believe that further evaluation is needed for these 'high-risk' patients, including colposcopy, cervical canal scraping, and endometrial pathological examination. Azodi et al. reported the treatment outcomes of 40 cases of in situ adenocarcinoma, with positive cervical canal margins after cold knife cone biopsy, LEEP, and laser cone biopsy at 24%, 75%, and 57% respectively. For patients with the desire for childbirth, the authors recommend CKC evaluation of in situ adenocarcinoma to exclude invasive adenocarcinoma. In addition, for in situ adenocarcinoma with negative cone biopsy margins and ECC, it is also advocated to perform type I hysterectomy. As there is no consensus on the management of ACIS and CIGN, it is advisable to provide appropriate management that is not identical to CIN after careful examination, comprehensive evaluation, and accurate diagnosis.

　　II. Prognosis

　　Richart pointed out that the higher the atypical degree of CIN, the deeper the involvement of the epithelial thickness, the greater the possibility of developing invasive cancer. Conversely, the lower the grade of CIN, the more opportunities there are for reversal to normal. CIN has three outcomes: ① Regression (or reversal); ② Persistent unchanged (or disease stabilization); ③ Progression (or cancerous change).

　　1. Related factors in the progression of CIN

　　(1) HPV types: Some studies suggest that HPV types are related factors in the progression of CIN (Richart et al., 1987). The risk of developing cervical cancer due to persistent high-risk HPV infection increases 250 times. Campion et al. (1986) followed up 100 cases of CINⅠ for more than 2 years, and 56% of those with positive high-risk HPV16, 18 types progressed to CINⅢ, while only 20% of those with positive low-risk HPV6 types had progression.

　　(2) The Degree of CIN: as the level of CIN increases, the probability of developing invasive carcinoma increases. Generally, 15% of CIN can develop into cervical cancer, among which the risk of CINⅠ,Ⅱ,Ⅲ developing into cancer is 15%, 30%, and 45% respectively, as shown in Table 7. Mill et al. (1992) reported that the risk of CINⅠ,Ⅱ,Ⅲ progressing to invasive carcinoma is 4 times, 14.5 times, and 46.5 times higher than that of normal women.

　　(3) Age: as age increases, the reversal rate of CIN lesions decreases. Mill et al. found that the total reversal rate of CIN patients aged 35 to 39 was 77%, and for those over 40, it was 61%.

　　(4) Other: such as intervention treatment for CIN, follow-up time, etc.

　　2. The Outcome of SPI

　　Most scholars believe that SPI has similar clinical and biological characteristics to CIN. Although there are controversies about the outcome of SPI at present, several reports since the 1980s suggest that HPV also has three outcomes, and they are related to the type of HPV. Rome and Chanan et al. (1987) reported 259 cases of untreated SPI, followed up for 18 months, among whom 16% had progression, 39% remained unchanged, and 45% regressed. Syrjanen et al. (1987) reported that among 513 cases of cervical cytology diagnosed with HPV type Ⅰ, 25% progressed to CIN, 60% remained unchanged, and 14% regressed.

　　3. The Outcome of Cervical In Situ Carcinoma

　　Most believe that in situ carcinoma can progress to invasive carcinoma, only a few can regress naturally or disappear after biopsy, and some authors believe that in situ carcinoma will not regress naturally. Mcindoe et al. (1984) reported 300 cases of untreated in situ carcinoma, followed up for 10 to 20 years, with a rate of progression to invasive carcinoma of 18% and 36% respectively. Yang Xuechang et al. (1992) observed 69 patients with in situ carcinoma who refused treatment, among whom 26% developed invasive carcinoma within an average of 5.2 years.