Cervical invasive cancer

　　1. Etiology

　　A large number of studies have been conducted on the epidemiological factors of cervical cancer both domestically and internationally, such as marital and reproductive factors, cervical erosion, smegma, etc. In recent years, research has focused on sexual behavior, sexually transmitted diseases, and viral etiology. The etiology includes:

　　1. Sexual behavior:Early age of first sexual intercourse, multiple sexual partners, and the sexual behavior of male partners are all considered to be related to the occurrence of cervical cancer. It is believed that this is related to the fact that the cervix is in the period of squamous metaplasia during adolescence, which is more sensitive to carcinogens.

　　More than 50 years ago, it was found that cervical cancer is extremely rare among nuns. Subsequent studies have indicated that factors such as marital and reproductive history, as well as sexual promiscuity, such as early first sexual intercourse, multiple sexual partners, and cervical cancer are closely related. In the 1970s, there were reports linking the mortality rate of cervical cancer to the incidence of gonorrhea, thus suggesting that most cervical cancers are caused by sexually transmitted diseases. Among these sexual factors, the number of sexual partners is the most consistently related to cervical cancer (Table 1), as listed in the case-control study results. The research findings indicate that women with cervical cancer have more sexual partners than the control group, and the risk of the disease is directly proportional to the number of sexual partners. The relative risk for those with ≥10 sexual partners is more than three times higher than for those with ≤1 sexual partners. The fact shows that multiple sexual partners are significantly associated with both CIN and cervical cancer, but the correlation with the former is more obvious. Slattery once estimated in a study that 36% of new cases of cervical cancer occur among those with ≥10 sexual partners. When the number of sexual partners is ≥6 and the age of first sexual intercourse is before 15 years, the risk of developing cervical cancer increases by 5 to 10 times or more.

　　流行病学研究还发现初次性交年龄为16岁者，其相对危险性为20岁以上的两倍（表2）。有学者指出初婚年龄在18岁以下者，比25岁以上者的患病率高13。3倍。Biswas（1997）报道初次性交年龄在12岁以下和≥18岁者相比，OR值为3。5，且与宫颈癌的关系不依赖其他因素而独立存在。

　　性关系的特征可能也影响宫颈癌的危险性。一些学者对不同年龄阶段的性伴侣数也进行了分析。Brinton（1987）及Herrero（1990）未发现20岁前的性伴侣数比终生性伴侣具有更多的意义，但Peter（1986）发现终生性伴侣的作用可全部归于20岁前多个性伴侣的作用，他还发现月经初潮及初次性交间隔时间短可提高危险性，较初次性交过早的单独作用还强，但后人未能证实。稳定的性伴侣（时间≥3个月），较不稳定的性伴侣对宫颈癌危险的相关性更大（Brinton，1987；Herrero，1990）。这个现象提示，可能需要更长期地、重复地接触携带性传播疾病的性伴侣，其危险性才增加。Herrero（1990）发现进行肛门性交者患宫颈癌的危险性亦增加，此种相关性是真实的还是仅仅反映了双方性行为的其他方面，还是与性卫生有关还不清楚。

　　2、人乳头瘤病毒感染：人乳头瘤病毒（humanpapillomavirus，HPV）感染是宫颈癌的主要危险因素。流行病学调查及临床资料分析显示，在目前发现的80余种HPV型别中约有30余型与性生殖道病变有关。

　　根据HPV致病力的大小及不同CIN和宫颈癌组织中HPV感染的分布情况，HPV分为高危型和低危型两大类。低危型多导致低度宫颈上皮内瘤变（CINI）及扁平疣类病变，主要有HPV6，11，30，39，42，43及44。高危型主要导致CINⅡ～Ⅲ及宫颈癌的发生，主要有HPV16，18，31，33，35，45，、52，56等。表3中所示与正常宫颈及CIN相比，宫颈浸润癌中HPV16及18型的阳性率最高，CIN次之。而HPV6/11型则多见于CIN中。HPV16、18型在CINⅡ、Ⅲ级中较常见，而HPV6，11型则在CINⅠ级中多见。HPV各亚型在宫颈浸润癌中的分布如表4，以16型最多见，其次为18型，45，31，33型占2％～5％。另有研究指出，宫颈腺癌中以HPV18型最常见，而与鳞癌关系最大的是HPV16型。

　　Reproductive tract HPV infection is mainly transmitted sexually, most common in sexually active young women, with the peak age range of infection being 18-30 years. As a common sexually transmitted disease, HPV infection is mostly transient. Most studies report that the natural clearance time of cervical HPV infection is about 7-12 months, with only a small portion being persistent infection. Many studies show that persistent high-risk HPV infection is a necessary condition for the occurrence of cervical lesions. It has been reported that the risk of developing CINⅢ in persistent high-risk HPV infection patients increases 100-300 times, while the risk of developing HGSIL (including CINⅡ and CINⅢ) in high-risk HPV-negative patients in the following 2 years is very small, and the cytological results during follow-up also changed from mild or borderline abnormalities to normal.

　　Dalstein et al. (2003) reported a prospective study on 781 women with normal/ASCUS/LSIL cervical cytology. The authors used second-generation hybrid capture (HCⅡ) to detect high-risk HPV (HR-IPV) in these 781 women and followed up every 6 months, with an average follow-up of 22 months. The results showed that the average duration of infection in high-risk HPV-positive patients was 7.5 months (3-42 months), and more than 50% of the infections were cleared within 7.5 months. Compared to high-risk HPV-negative patients, HPV transient infection and persistent infection patients had a higher possibility of developing cervical cytology ASCUS and SlL, with relative risks (RR) of 2.38 and 9.13, respectively, and all patients progressing to CIN2/3 or above were persistent high-risk HPV infection patients. At the same time, the authors found that compared to high-risk HPV-negative patients, women with low to moderate viral load of high-risk HPV and those with high viral load were more likely to have cervical cytology abnormalities, with relative risks (RR) of 1.65 and 8.66, respectively.

　　Schlecht et al. (2001) reported the results of a prospective study on the persistence of HPV infection. The study conducted HPV and cervical cytology examinations on 1611 women from 1993 to 2000, with examinations every 4 months in the first year and twice a year thereafter, defining the initial consecutive two positive HPV-DNA tests as persistent infection. The results showed that the relative risk of developing SIL for patients with persistent infection of HPV16 or 18 was 8.68 (95% CI, 5.9-17.6) compared to those with HPV-negative patients; and the relative risk of any high-risk HPV persistent infection developing SIL was 10.17, and the relative risk of developing HSIL was 11.6 compared to those with high-risk HPV-negative patients.

　　The incidence of HPV infection in the reproductive tract has明显 increased in the past 30 years, with the incidence of HPV infection in the Rockester area of the United States rising 8-fold from 1950 to 1978, reaching 106 per 100,000 in 1978 (Chuang, 1984). The number of patients seeking medical treatment for condyloma acuminata in the United States increased 4.5-fold from 1966 to 1984.

　　The survey results in different regions of 6 provinces and cities in China found that the positive rate of HPV16 type DNA detection in cervical cancer tissues by nucleic acid hybridization method was 36% to 64%. Shanxi Province, a high-incidence area, was 64%, and Sichuan Province, a low-incidence area, was 36%. There was a significant difference in the detection rate of HPV16 between the two regions (Zhang Wenhua, 1987). The survey results of Si Jingyi et al. (1992) on cervical cancer in high-incidence areas such as Xinjiang and North China, medium-incidence areas such as Hubei and Heilongjiang, and low-incidence areas such as Guizhou showed that the average positive rate of HPV16 type in cervical cancer was 60.4%, and there was a significant difference in the positive rate of HPV16 in cervical cancer in various regions, which was consistent with the mortality level of cervical cancer in various regions. For example, in Xinjiang, it was as high as 77% (mortality rate of 15.78/100,000), while in Guizhou it was 45% (mortality rate of 4.92/100,000). Further analysis found that the positive rate of HPV16 in rural cervical cancer in Xinjiang was 88%, significantly higher than that in urban areas (66%).

　　Several case-control studies have shown that HPV infection is closely related to the occurrence of CIN and cervical cancer. In a large case-control study conducted in four countries in Latin America, including 759 cases of cervical invasive cancer and 1467 controls, HPV6/11, 16/18 were detected by FISH, the results show that there is a significant correlation between HPV16/18 and cervical cancer. The relative risk is highest when both HPV6/11 and HPV16/18 are positive, and it is also observed that the effects of sexual behavior and HPV infection are independent of other factors (Reeves, 1989).

　　Two case-control studies in the United States (Manos, 1991; Morrison, 1991) also indicate that HPV infection is strongly associated with CINⅠ-Ⅲ. The risk is higher when multiple types of HPV infection coexist. After adjusting for HPV infection factors, the correlation between early first sexual intercourse, multiple sexual partners, oral contraceptives, and smoking disappeared or significantly decreased in both groups. Eileen's 2003 review of the literature suggests that there are different types of HPV coinfections in reproductive tract HPV infections, with a coinfection rate of up to 39%, and coinfections are associated with the severity of lesions. Multiple infections can be seen in approximately 11.8% of women with normal or atypical squamous cells (ASCUS) and 35.4% of women with mild to moderate atypical hyperplasia, and at least one of them is a high-risk HPV type.

　　Schellekens et al. detected 12 types of HPV-DNA in 74 cervical cancer samples, with a HPV infection rate of 96%, 14.1% were infected with 2 to 3 types of HPV, among which at least one was a high-risk type of HPV. At the same time, it was found that multiple infections were more common in adenocarcinoma than in squamous cell carcinoma and adenocarcinoma (P=0.014).

　　Morrison (1991) also pointed out that the risk increases with the increase of viral load, and there is a statistically significant dose-response relationship between the two. Munoz et al. (1992) conducted case-control studies in Colombia and Spain in recent years, using three different hybridization methods to detect HPV-DNA. In both countries, a strong correlation was found between HPV and cervical cancer, and it was observed that the risk of cervical cancer also increased with the increase of viral load. Josefsson et al. reported in 2000 the results of HPV16 viral load measurement in 478 cases of cervical in situ cancer and 608 normal controls using PCR technology. They divided the patients into five groups according to the viral load from low to high, and compared with HPV16-negative cases, the OR value for the occurrence of cervical in situ cancer gradually increased from the low-level viral load group to the high-level viral load group, respectively, 2.0, 4.4, 8.1, 18.7, and 68.8. Ho et al. followed up 100 women in 1999, with a follow-up every 6 weeks for the first 3 months, and then every 3 months, for a total of 15 months, defining consecutive two HPV-positive as persistent infection. Persistent HPV infection is associated with the persistent presence of SIL, with an OR of 3.91 (95% CI, 1.58-9.65), while the OR for persistent high viral load is 4.97 (95% CI, 1.45-17.02). After adjusting for HPV factors, oral contraceptives, early first sexual intercourse, and low education level were still closely related to cervical cancer.

　　Quasi-experimental studies are an ideal method to determine the natural relationship between HPV and cervical cancer. Campion (1986) observed 100 women with CIN for 2 years, using FISH to detect HPV-DNA every 8 months. The results showed that 56% of HPV16/18 positive cases developed into CIN III, while only 20% of HPV6 positive cases did so. Schneider (1987) also reported similar findings. Interestingly, 3 cases of cervical CINⅠ-Ⅱ with HPV16/18 infection disappeared after their partners eliminated HPV16-type infection. Finland followed up 530 women with HPV-positive cervical cancer for an average of 60 months, using cellular atypia and HPV type as indicators of disease progression. The results indicate that HPV16 type is more likely to induce the progression of CIN than other types (HPV16 type with 45% progression, HPV18 type with 27%, HPV6/11 with 0 and 13% respectively) (Syranen, 1990). Murthy (1990) found that in 63 women who progressed from CIN to CIS, the HPV16/18 positivity rate in biopsy specimens diagnosed with CIS was 68.3%. In 44 women with no progression, the HPV16/18 positivity rate at the end of follow-up was 27.3%, with an OR of 5.9, which was statistically significant.

　　The investigation and research by the Cancer Hospital of the Chinese Academy of Medical Sciences in the high-incidence area of cervical cancer in Xiangyuan County, Shanxi Province, shows that high-risk HPV infection of the genital tract is the main risk factor for cervical cancer and cervical intraepithelial neoplasia in local women. In the investigation of 1997 married women aged 35 to 45, there were 12 cases of cervical cancer, 31 cases of CINⅢ, 43 cases of CINⅡ, and 127 cases of CINⅠ. The infection rate of HPV for cervical invasive cancer and CINⅢ was 100% (12/12, 31/31), for CINⅡ was 95.3% (41/43), for CINⅠ was 61.4% (78/127), and for the normal population was 14.2% (253/1784). Bosch and Manos et al. through collecting 1008 cervical cancer biopsy specimens from 22 countries for PCR detection found that HPV-DNA could be detected in 93% of the tumors, and there was no significant difference between countries (Bosch FX, 1995). Recently, Manos et al. (Walboomers JM, 1999) reanalyzed the HPV-negative cases in the study, combined with previous data, excluding the factor of insufficient sample size, and found that the detection rate of HPV in cervical cancer worldwide reached 99.7%.

　　In summary, the etiological relationship between HPV and cervical cancer can be summarized as follows: ① The above studies show that the correlation between the two is strong and consistent; ② The correlation is mainly manifested in a few special types of viruses, that is, high-risk types.

　　3. Menstrual and Delivery Factors:There have been few reports on the relationship between menarche age, menopausal age, and hygiene factors with cervical cancer. Zhang et al. (1989) pointed out that in rural China (Jing'an County), poor hygiene (such as not washing the vulva) and prolonged menstrual periods significantly increase the risk of cervical cancer. Another survey also found that poor hygiene during menstruation and postpartum periods, with an RR of 2.27 (Liao Caisen, 1986) between the case group and the control group, had a significant statistical significance. In addition, more and more facts show that multiple births are closely related to cervical cancer. Many provinces and cities in China report that the lowest incidence rate of the disease is 11.038 per 100,000 after 1 to 3 deliveries, gradually increasing to 19.236 per 100,000 after 4 to 6 deliveries, and significantly increasing to 37.752 per 100,000 after 7 or more deliveries (Yang Dawang, 1985). Brinton (1989) in the survey of Latin America found that after adjusting for socio-economic factors and sexual factors, the risk of cervical invasive cancer in women with ≥12 deliveries was 4 times higher than that in women with 0 to 1 deliveries. Wang (1996) reported that in the Taiwan region of China from 1991 to 1994, the data showed that the risk of women with ≥4 vaginal deliveries was twice as high as that with ≤1. This correlation may be due to the trauma to the cervix during delivery and the effects of endocrine and nutrition during pregnancy. In addition, it was also found that the detection rate of HPV in pregnant women was very high, which is likely due to the decreased immune function during pregnancy, which promotes the activity of the virus.

　　4、男性性行为及有关因素：一些研究说明男性性行为与宫颈癌关系密切。一些学者对比了宫颈癌及健康妇女配偶的性行为及其他行为方面的特点，以研究男性在宫颈癌发病中的作用。所有这些研究均得出了一致的结论：即宫颈癌配偶的性伴侣数远较对照组配偶的性伴侣数为多。研究还指出宫颈癌患者的配偶大多有各种性病史，包括生殖器疣、淋病、生殖器疱疹，而配偶经常用避孕套的妇女则宫颈癌危险性低。对靖安县415例宫颈癌的队列研究结果表明，随着初次性交年龄的提前、本人及丈夫婚外性伴侣的增加，宫颈癌的相对危险性亦上升，丈夫有两个婚外性伴侣者，其妻子宫颈癌的相对危险性上升5倍，306对配对调查（廖彩森，1986）也说明本人及配偶性混乱不论在配对调查中或高、低发区正常人群的对比调查中，病例组均高于对照组，高发区高于低发区。

　　一些学者又进一步研究了宫颈癌的危险度和配偶性行为类型的关系。在欧洲、泰国及中国台湾地区的一些研究者发现，宫颈癌的高度危险性和其配偶嫖娼的次数有关（Buckley，1981；Kjaer，1991；Wang，1996）。Reeves及Quiroz（1987）报道，在拉丁美洲男性配偶嫖娼可以影响性病的流行，因此在高发区更重要的是调查上述性行为的情况，最具说服力的证据是一夫一妻制的妇女患宫颈癌的危险性和她丈夫的性伴侣数直接相关（Buckley，1981）。Skegg（1982）认为传统上婚前保持贞操的妇女（印尼穆斯林）宫颈癌的发病率很高，这是因为其丈夫嫖娼而将致癌因子传给了这些妇女所致。男性生殖器HPV感染与其配偶患宫颈癌的危险亦密切相关。Barrasso等（1987）用阴道镜检查了294例患宫颈扁平湿疣及186例宫颈上皮内瘤变患者的男性伴侣480例，其中64％的男性生殖器有尖锐湿疣及丘疹。宫颈上皮内瘤变患者的性伴侣中32。8％（61例）亦同时有阴茎上皮内瘤变，而扁平疣患者的性伴侣中则仅有1。4％（4例）。60例阴茎丘疹患者中60％（36例）检测出HPV-DNA序列，几乎全部阴茎上皮内瘤变中均发现HPV16及33型，而HPV6，11及42型则只存在于湿疣中。上述事实亦支持宫颈癌及其癌前病变和其男性性伴HPV感染相关的看法。

　　There are also many reports on the impact of male penile cancer on the spouse's cervical cancer. In the death review survey in China in the 1970s, it was found that the consistency of the geographical distribution of the two cancers is statistically very significant (P

　　There is no clear conclusion on the relationship between male circumcision and cervical cancer. Some scholars have statistics that the relative risk of cervical cancer in the wives of circumcised men is extremely low (RR 0.3).

　　5. Smoking:Smoking may be one of the risk factors for cervical cancer. Different epidemiological studies have shown that the risk of invasive precancer and invasive cancer is increased in smokers. After controlling other various factors, it was found that the impact of smoking still exists. In most studies, the risk of cervical cancer in smokers increased by twice, and most high-risk patients are long-term heavy smokers, and it is suggested that there may be a late effect. It is believed that the effect of smoking is only manifested in squamous cell carcinoma patients, and is unrelated to adenocarcinoma or adenosquamous carcinoma. In the detection of cervical mucus in smokers, it was found that the nicotine and cotinine content caused by smoking is very high. Some studies have shown that the number of years smoked, the amount smoked per day, and the age of initial smoking are all related to cervical cancer. Although the inhibitory effect of smoking on the body's immune system should be considered, its biological effects should also be considered, especially that smoking enhances the effects of infectious factors including HPV. ZurHausen (1982) believed that further research is needed on the promotional effect of smoking on HPV.

　　6. Contraceptive methods:The relationship between oral contraceptives and the risk of cervical cancer is influenced by various factors, especially the influence of sexual behavior. Most studies, after considering the effects of relevant factors, have proved that the risk still increases. For those who have taken oral contraceptives for ≥8 years, the risk increases by a factor of 2. Some studies have indicated that the risk of adenocarcinoma in users of oral contraceptives is higher, which is consistent with the increase in the incidence of adenocarcinoma in young women shown in descriptive surveys. The risk of cervical cancer in users of barrier contraception methods (uterine cap, condom) is very low, and it is speculated that this is probably due to a reduction in the opportunity to come into contact with infection, and the protective effect of the uterine cap may be partly due to the simultaneous use of spermicides with antiviral effects.

　　7. Herpesvirus Type Ⅱ (HSV-Ⅱ) and others:HSV-Ⅱ is a virus that was first considered to play an important role in the etiology of cervical cancer. Some units in China have conducted serological epidemiological investigations on HSV-Ⅱ and cervical cancer using various methods, finding that the positivity rate of HSV-Ⅱ antibodies in cervical cancer patients is as high as over 80%, while in the control group it is only 14% to 57.14%. The antigen positivity rate is also much higher than that of normal controls and chronic cervicitis. Detection by in situ hybridization and HSV-Ⅱ DNA probe also found that the HSV-Ⅱ DNA-related sequences in cervical cancer tissues are much higher than those in normal cervical tissues. In addition, HSV-Ⅱ virus particles have been isolated from cervical scraping specimens of cervical cancer patients in Hubei, Hunan, Jiangxi, Beijing and other places, and most of them have been identified as HSV-Ⅱ type. Some scholars have conducted research on cell transformation and mouse-induced cervical cancer using the isolated virus strains, all with positive results. The detection of HSV-Ⅱ antigen and serology in cervical exfoliated cells of urban and mountainous (high-incidence) populations and cervical cancer patients by PAP method has proved that the infection rate of HSV-Ⅱ in mountainous areas is high, and the positivity rate of HSV-Ⅱ antigen in cervical cancer and precancerous lesions in mountainous areas is higher than that of local normal people, indicating that the incidence of cervical cancer is high in areas with HSV-Ⅱ prevalence. Further research has found that the antibody titer of HSV-Ⅱ is significantly higher in high-incidence areas than in urban areas, and the geometric mean of HSV-Ⅱ antibody titer in male serum also shows a significant difference between the two places. Some studies have found that the level of HSV-Ⅱ antibody in serum is significantly correlated with the mortality rate of cervical cancer.

　　Some foreign studies have also observed that the incidence of CIN, CIS, and invasive cancer is higher in women with HSV-Ⅱ antibody positivity than in normal women, and the correlation between HSV-Ⅱ and cervical invasive cancer is stronger than that of CIN. Two studies in the United States (Graham, 1982; Thomas, 1978) showed that the risk of CIS and invasive cancer in HSV-Ⅱ antibody-positive individuals increased after adjusting for other confounding factors. Another case-control study of 23,000 women showed that the risk of cervical cancer in women with HSV-Ⅱ antibody positivity increased by twice (Choi, 1977), but the two similar studies by Vonka (1984) and Adam (1985) failed to prove the correlation. Armstrong (1986) observed a transient positive correlation between HSV-Ⅱ infection and CIN in young women visiting sexually transmitted disease clinics, but this correlation was not confirmed by cytological examination. In a random survey of women in Denmark and Greenland, the results showed that the positivity rate of HSV-Ⅱ antibodies in Greenland women (where the incidence of cervical cancer is 6 times higher than in Denmark) was higher than that in Denmark.

　　In summary, although the etiological relationship between HSV-Ⅱ and cervical cancer cannot be confirmed, it cannot be excluded, especially in terms of possible interactions with HPV. Hildesheim et al. (1991) found that HSV-Ⅱ has a synergistic effect with HPV. Compared with those who are negative for both viruses, the RR of HSV-Ⅱ positive individuals is 1.2, and the RR of HPV 16/18 positive individuals is 4.3. When both HSV-Ⅱ and HPV 16/18 are positive, the RR is 8.8. Meng Xiangjin et al. (1989) used DNA hybridization and PAP methods to simultaneously detect HPV-DNA and HSV-Ⅱ antigen in 50 cases of chronic cervicitis, CIN, and cervical cancer. In some cases, both viruses were present, suggesting that there may be some association between them.

　　Other sexually transmitted diseases related to cervical cancer, such as syphilis, gonorrhea, trichomoniasis, and trachoma, have all been reported, but there have also been opposite results. Some scholars have conducted detection and analysis of five infectious diseases, HPV, HSV-Ⅰ, Ⅱ, HCMV, and Chlamydia, in cervical cancer and control groups, and found that HPV, HSV, HCMV, and Chlamydia infections are strongly associated with cervical cancer. The risk increases with the increase in the types of infection. 35.5% of the patients have 4 or more infections, while the control group has none.

　　2. Pathogenesis

　　1. Pathological characteristics:According to the origin of the tumor, the main pathological type of cervical invasive carcinoma is squamous cell carcinoma, adenocarcinoma, and undifferentiated carcinoma. In recent years, there has been an increasing trend in cervical adenocarcinoma and mucinous adenocarcinoma. The reason is that the routine staining has increased the mucin staining, and it is found that the squamous cell carcinoma tissue in the slices stained with mucin is actually poorly differentiated adenocarcinoma or adenosquamous carcinoma. Therefore, the definition of squamous cell carcinoma is no longer just the tumor resembling stratified squamous epithelium, but should be clearly defined as: Squamous cell carcinoma refers to a type of cancer that has flat epithelial differentiation, i.e., keratinization and cell bridges, without glandular differentiation or mucin secretion. The absence of glandular differentiation or mucin secretion is very important, and these two points can exclude poorly differentiated adenocarcinoma and adenosquamous carcinoma. This new classification not only corrects the diagnosis, tissue genesis, and proportion of different pathological types of cervical cancer, but more importantly, points out the prognosis for clinical practice. Because low-differentiated adenocarcinoma and adenosquamous carcinoma have high malignancy, poor prognosis than squamous cell carcinoma, and mostly occur in young patients, which are the main reasons for poor prognosis and rapid metastasis. From the current clinical diagnosis, squamous cell carcinoma accounts for about 70%, adenocarcinoma accounts for about 20%, and adenosquamous carcinoma accounts for about 10%. In addition, squamous cell carcinoma also has subtypes such as verrucous squamous cell carcinoma, papillary squamous cell carcinoma, etc. Adenocarcinoma has subtypes such as papillary adenocarcinoma, endometrioid adenocarcinoma, clear cell carcinoma, etc., which are all rare in clinical practice.

　　(1) Differentiation degree of cervical squamous cell carcinoma: According to the histological morphology of cervical squamous cell carcinoma, the differentiation degree is summarized into 3 grades, namely: high differentiation, intermediate differentiation, and low differentiation. 50% to 60% of cervical cancers are of intermediate differentiation, while the rest are equally divided between high and low differentiation.

　　① High-differentiated squamous cell carcinoma (squamous cell carcinoma grade I): large cells, with obvious keratin pearl formation, visible cell bridges, less atypical cancer cells, fewer nuclear divisions, and no abnormal nuclear division.

　　② Intermediate-differentiated squamous cell carcinoma (squamous cell carcinoma grade II): large cells, with obvious cell atypia, deeply stained nuclei, irregular, high nuclear-cytoplasmic ratio, more frequent nuclear division, not obvious cell bridges, with a few or no keratin pearls, and single dyskeratotic cells.

　　③ Low-differentiated squamous cell carcinoma (squamous cell carcinoma grade III): large or small cells, without the formation of keratin pearls, nor cell bridges, occasionally scattered single dyskeratotic cells can be found, cell atypia and nuclear division are common, this type of cancer is not easy to be diagnosed as squamous cell carcinoma, but it can be distinguished by immunohistochemistry and electron microscopy. Some low-differentiated squamous cell carcinomas are confirmed to be adenocarcinoma or adenosquamous carcinoma by mucin staining. The stroma around the cancer nests may have varying amounts of lymphocytes, plasma cells, or eosinophils infiltrating. From a histological perspective, a large number of lymphocytes or eosinophils infiltrating have a better prognosis.

　　Under the microscope, most squamous cell carcinomas show a reticular infiltration of stroma in the tumor cells in a cord-like pattern. It also shows various tumor states, cell morphology, and differentiation degrees. The cervical stroma separated by cord-like malignant cells is infiltrated by lymphocytes and plasma cells. These cancer cells can be further divided into keratinizing and non-keratinizing types.

　　Keratinizing squamous cell carcinoma is composed of characteristic whirlpool-like epithelial cells containing central keratinocyte nests (keratin pearls) (Figure 2). The nuclei are large, the chromatin granules are coarse, the nuclei are deeply stained, and there are obvious cell bridges, in addition to transparent keratinous granules and keratinization of the cytoplasm. Only a few mitotic figures are visible.

　　Non-keratinizing squamous cell carcinoma (Figure 3) is characterized by irregular, swollen polygonal cells with serrated infiltration of the stroma, possibly with dyskeratosis and intercellular bridges. There is obvious polymorphism of cells and nuclei, frequent mitotic figures, and no keratin pearls.

　　Other less common types of squamous cell carcinomas include: warty squamous cell carcinoma (also known as verrucous squamous cell carcinoma), papillary squamous cell carcinoma, lymphoepithelioma-like carcinoma, and squamous clear cell carcinoma.

　　Whether it is cervical squamous cell carcinoma or adenocarcinoma, the presence of vascular tumor emboli is evidence of potential invasive growth and is related to the risk of regional lymph node metastasis. Occasional vascular invasion is a sign of poor prognosis and is related to distant metastasis or hematogenous metastasis. Although the cytological features of invasive cervical cancer have been well described, cytology is not a reliable method for diagnosing invasive lesions. The confirmation of lesions in cytological smears requires rich experience, as there are only a few cancer cells among the fragments of cervical cells and blood cells in a single cervical smear. Cervical adenocarcinoma is difficult to identify by cytologists: it can only be detected by cytologists when the cells are extremely atypical. The recognition of individual cell types is more complex. Therefore, the final diagnosis of cervical invasive cancer always relies on histopathological diagnosis. Tissue samples around the tumor are the best for diagnosis, as they are more likely to contain morphologically complete tumor tissue. Biopsy specimens taken from the center of the tumor may contain necrotic tissue, affecting the accuracy of histopathological diagnosis.

　　(2) Gross types of cervical squamous cell carcinoma: According to the growth pattern and morphology of the tumor, there are the following 4 types of gross types of cervical squamous cell carcinoma:

　　① Erosive type: the cervix has visible erosion without visible tumor, with a rough, granular surface, and relatively hard texture. It is easy to bleed upon palpation, and this type is more common in early invasive cancer.

　　② Nodular type: exogenous tumor, the cancer grows from the external orifice of the cervix to the surface of the cervix, forming nodular masses, or multiple nodules融合 together to form large masses, with obvious protuberances. The tumor mass is uneven, often accompanied by shallow and deep ulcers, with relatively hard or hard texture, and bleeding upon palpation.

　　③ Cabbage-like type: also belongs to exogenous tumors, the cancer grows like a cauliflower from the cervix into the vagina, with a large tumor mass, rich blood vessels, and relatively脆 texture. There is obvious bleeding upon contact, often accompanied by infection and the presence of necrotic foci. This type of cancer tends to less frequently invade the para-cervical tissue, and the prognosis is relatively better.

　　④ Ulcerative type: belongs to endogenous tumors, the cancer grows invasively from the cervix into the uterine cavity, forming ulcerative foci and cavities. Sometimes, the entire cervix and vaginal fornix tissue can ulcerate and completely disappear, with irregular edges, necrotic tissue, and relatively hard texture. The secretions have a foul smell. This type is more common in patients with weak physique, thin body shape, and poor general condition.

　　According to the law of tumor development and postoperative pathological examination of the specimen, intraperitoneal metastasis is more common in vascular and lymph node metastasis, and intraperitoneal metastasis often has invasion of the cervical canal and uterine body, while exogenous tumors invading the uterine body are less common.

　　Generally speaking, adenocarcinoma occurs more frequently in the cervical canal, grows outward to form a barrel shape, and the tumor cells have the characteristics of glandular epithelial cells, forming glandular structures and infiltrating the stroma. Squamous cell carcinoma occurs more frequently on the surface of the cervix, especially at the squamous-columnar junction of the epithelium. Understanding the growth pattern and gross pathological typing of the tumor, combined with clinical staging, is of reference value for determining the treatment plan and judging the prognosis.

　　2. Clinical Staging:The clinical staging of cervical cancer began in 1929, and the staging criteria were formulated by the International Federation of Gynecology and Obstetrics (FIGO), the American Cancer Society (AJCC), and the Union for International Cancer Control (UICC). The purpose of staging is to have a unified evaluation standard for the results of treatment from different hospitals and different methods, so that statistical data can be comparable. Strict and accurate clinical staging can select appropriate treatment plans based on the scope of the lesion, correctly evaluate the therapeutic effect, and judge the prognosis.

　　(1) Staging Principles:

　　① The clinical staging should be determined by experienced physicians before treatment based on careful clinical examination. Pelvic examination and bimanual examination are of special importance. Once the staging is established, it cannot be changed due to new findings after treatment.

　　② The basis for determining the staging is to conduct detailed clinical examinations: these examinations include visual inspection, palpation, colposcopy, cervical canal scraping, hysteroscopy, cystoscopy, rectoscopy, intravenous pyelography, X-ray examination of the lungs and bones. For those suspected of being affected by the rectum or bladder, pathological examination for confirmation is required.

　　③ Angiography, lymphography, and laparoscopy are helpful in determining the treatment plan, but the problems found should not be used as the basis for determining the staging.

　　④ When it is impossible to determine the specific stage, the staging should be set at the earlier stage.

　　(2) Clinical Staging: The clinical staging of cervical cancer has a history of over 70 years, having undergone several revisions and gradual improvements. Initially, when the tumor infiltrates the pelvic wall, it was classified as stage IV, or 'frozen pelvis'; however, during the staging revision in 1937, it was reclassified as stage III. In 1950, the revision of staging decided not to use the invasion of the uterine body as a staging criterion (the original staging classified the invasion of the uterine body as stage II); in 1961, the staging criteria clearly defined stage 0 cancer as in situ cancer and intraepithelial cancer, and pointed out that cases of stage 0 cancer were not included in any treatment statistics. In 1970 and 1985, the concept of occult cancer (OCC) emerged, and renal pelvis hydrops or renal dysfunction were added to stage III. Subsequently, explanations were also provided for the criteria of stage 0 and stage IV. In 2003, at the FIGO meeting held in Santiago (Chile), the staging criteria for stage I were revised again. The clinical staging criteria for cervical cancer after this revision are the unified staging criteria used internationally at present, as follows (Figure 4):

　　Stage 0: In situ cancer, intraepithelial cancer (cases in this stage are not included in any treatment statistics).

　　Stage I: The lesion is confined to the cervix (whether the corpus uteri is involved is not considered).

　　Stage Ia: The invasive cancer is only identifiable under the microscope. Any visible lesion, even superficial invasion, belongs to stage I b; the depth of stromal invasion

　　Stage Ia1: The depth of stromal invasion

　　Stage Ia2: The depth of stromal invasion is 3-5 mm, width

　　Stage I b: The clinical examination shows the lesion is confined to the cervix or the preclinical lesion is larger than stage Ia.

　　Stage I b1: The clinical lesion diameter

　　Stage I b2: The clinical lesion diameter is greater than 4 cm.

　　Stage II: The lesion extends beyond the cervix but not to the pelvic wall, and the vaginal invasion does not reach the lower third of the vagina.

　　Stage IIa: There is no obvious parametrial invasion.

　　Stage IIb: There is obvious parametrial invasion.

　　Stage III: The lesion has infiltrated the pelvic wall, there is no space between the tumor and the pelvic wall during rectal examination; the cancer involves the lower third of the vagina; there is hydronephrosis or renal dysfunction without other causes.

　　Stage IIIa: The lesion has not reached the pelvic wall, but involves the lower third of the vagina.

　　Stage IIIb: The lesion has reached the pelvic wall or there is hydronephrosis or renal dysfunction.

　　Stage IV: The lesion has exceeded the true pelvis or has infiltrated the mucosa of the bladder or rectum clinically.

　　Stage IVa: The lesion has spread to adjacent organs.

　　Stage IVb: The lesion has metastasized to distant organs.

　　(3) Points to note for staging:

　　① Stage 0 includes atypical cells in the full thickness of the epithelium, but without stromal invasion.

　　② The diagnosis of stage Ia (Ia1 and Ia2) must be determined based on microscopic observation.

　　③ The diagnosis of stage III should be made when the parametrial invasion reaches the pelvic wall, there is no space between the tumor and the pelvic wall, and the thickening is nodular.

　　④ Even if classified as stage I or II based on other examinations, if there is a cancerous ureteral stricture causing hydronephrosis or renal dysfunction, it should be classified as stage III.

　　⑤ Bladder bullous edema cannot be classified as stage IV. If bladderoscopy shows elevation and grooves, and it can be confirmed at the same time that the elevation or groove is fixed with the tumor through the vagina or rectum, it should be considered as invasion of the submucosa of the bladder. When malignant cells are found in the bladder lavage fluid, a biopsy of the bladder wall should be taken for pathological examination to confirm.

　　3. Points to note for staging:The main route of metastasis for cervical invasive cancer is direct spread and lymphatic spread, with hematogenous spread being rare, but several conditions can coexist in advanced cases.

　　(1) Direct spread: This is the most common way of cervical cancer spread. The tumor invades downward from the cervix, with the fornix being most susceptible. Due to the shallow anterior fornix, invasion of the anterior vaginal wall occurs earlier than the posterior vaginal wall. Once the fornix is involved, the tumor can rapidly spread to the vagina, sometimes showing intermittent or jumping spread. Upward spread can invade the corpus uteri, which occurs relatively late. Since the parametrial tissue is relatively loose and rich in lymphatic vessels, it is easily involved. The tumor spreads along the parametrial tissue and the cardinal ligament from both sides of the cervix, and along the uterosacral ligament posteriorly, forming metastatic foci in the form of plaques, string-like, nodular, or mass-like. It often appears simultaneously with lymph node metastasis. The tumor invades the bladder anteriorly and the rectum posteriorly.

　　In clinical practice, tumor infiltration often coexists with inflammation, and it is necessary to differentiate after systemic anti-inflammatory treatment. Therefore, tissue thickening during pelvic examination is not necessarily cancer infiltration. Only when the paracervical tissue becomes hard, forming nodules, masses, loss of elasticity, or thick fibrous strands, can it be diagnosed as cancer infiltration.

　　(2) Lymphatic metastasis: It is the main route of metastasis for cervical invasive cancer. The tumor spreads along the small lymphatic vessels in the paracervical tissue to the obturator area, then to the common iliac lymph nodes through the internal and external iliac vascular areas, and finally to the celiac lymph nodes around the abdominal aorta. In some cases, it can even ascend to the supraclavicular lymph nodes or retrogradely metastasize to the inguinal lymph nodes. This situation is more common in late cases. The tumor can also spread to the pre-sacral lymph nodes along the lymphatic vessels in the uterosacral ligament. When the tumor invades the lower third of the vagina or the vulva, it spreads to the inguinal lymph nodes along the lymphatic pathways. Figure 5 shows the lymphatic metastasis pathways of cervical cancer.

　　The incidence of lymph node metastasis is proportional to the clinical stage, that is, it rises with the increase of clinical stage (Liu Chiming, 1994). However, it has been found in clinical practice that some very early cases have lymph node metastasis, and some late cases have no lymph node metastasis, which may be related to the body's lymphatic immune function.

　　(3) Hematogenous dissemination: It is relatively rare. Once hematogenous dissemination occurs, it forms distant metastatic foci. Common sites of metastasis are the lungs, liver, bones, and brain. This situation often occurs in cases of advanced cervical cancer, and it is more common in small cell squamous cell carcinoma.

　　Cancer rapidly invades the vagina, invades the corpus uteri in the late stage, and is complicated with infection. The extensive surgery for radical hysterectomy has a wide surgical range and much trauma, so complications are likely to occur during surgery. Common complications include:

　　I. Organ injury during surgery:The uterus is located in the central part of the pelvic cavity, with the bladder in front and the rectum behind. There are many great pelvic vessels around it, so regardless of which type of radical surgery, it is possible to damage the surrounding organs of the uterus, the most common being the injury to the intestinal loops or bladder.

　　II. Bleeding during surgery:The bleeding during radical hysterectomy can be divided into two aspects: one is during the dissection of lymph nodes, where slight carelessness can directly damage arteries or veins around the great pelvic vessels; the other is during the dissection of the cardinal ligament or the free ureteral tunnel, which can lead to bleeding from the pelvic venous plexus. At this time, it is difficult to identify the bleeding point.

　　III. Postoperative complications:

　　1. Postoperative bleeding:Postoperative bleeding is rare because all blood supplies in the pelvic cavity have been hardened after surgery, and the chance of rebleeding is relatively low.

　　2. Urological complications

　　(1) Bladder complications: Fistula formation: If the patient has not received radiotherapy before surgery, it is not common to form a vesicovaginal fistula due to bladder ischemia.

　　(2) Ureteral complications: Ureteral injury is the most serious complication. It is easy to damage the ureteral wall or affect its local blood supply during the dissection of the free ureter. In addition, postoperative secondary infection, poor urination, and other factors can lead to necrosis and shedding at the local site of ureteral injury or due to vascular insufficiency, resulting in ureteral vaginal fistula, vesicovaginal fistula, and extraperitoneal urinary leakage.

　　3, Pelvic lymph cyst:After pelvic lymph node dissection, an invalid cavity remains retroperitoneally, and the refluxed lymphatic fluid accumulates retroperitoneally to form a cyst, known as a pelvic lymph cyst. After a complete and thorough lymph node dissection, there is fluid accumulation in the retroperitoneal space, the composition of which is similar to the exudate on the surface of a third-degree burn, containing blood, lymph, and tissue fluid, with a high concentration of protein. After extensive hysterectomy, a drainage tube should be placed in the retroperitoneal space to aspirate the fluid, the purpose of which is to remove the accumulated large amount of fluid. The drainage tube placed after surgery should be flushed with sterile normal saline to maintain patency.

　　4, Infection:With the rapid development of antibiotics, broad-spectrum antibiotics are given before or during extensive surgery or after surgery as a preventive and therapeutic measure. The incidence of severe infection or severe pelvic adnexal cellulitis after surgery has significantly decreased, in addition to sufficient drainage at the surgical site. The incidence of pelvic adnexal cellulitis after extensive hysterectomy has significantly decreased, about 5% or less. If secondary infection occurs despite the use of prophylactic antibiotics, cultures of the fluid in the vaginal apex and abdominal drainage tubes should be performed. If pathogenic bacteria are found, antibiotics should be selected based on drug sensitivity tests.

　　5, Venous thrombosis and pulmonary embolism:Patients who undergo a radical hysterectomy may develop lower limb venous thrombosis, and the causes include:

　　(1) Changes in blood coagulation after surgery.

　　(2) Venous wall damage.

　　(3) Venous blood stasis.

　　The severity of clinical symptoms and the stage of the disease are related to the early or late stage of the disease. Cervical cancer may be asymptomatic in the early stage. As the disease progresses and the tumor grows in different ways, symptoms gradually appear. The main clinical symptoms of cervical invasive cancer are irregular vaginal bleeding, increased vaginal discharge, and pain. The severity of these symptoms is directly related to the stage of the lesion, the growth pattern of the tumor, the histopathological type, and the overall condition of the patient.

　　Irregular vaginal bleeding is a major clinical symptom of cervical cancer patients, accounting for 80% to 85%. Especially, vaginal bleeding after menopause should be paid more attention to. Vaginal bleeding is often caused by the rupture of tumor blood vessels, especially in cauliflower-type tumors, which show bleeding symptoms earlier and in greater quantities. If bleeding occurs frequently, excessive blood loss can lead to severe anemia. In advanced cases, massive vaginal bleeding can cause shock, which is more common in tumors with invasive growth.

　　Increased vaginal discharge is also a major symptom of cervical cancer patients, which often occurs before vaginal bleeding. In the early stage, vaginal discharge may have no smell. As the tumor grows, the cancer tissue undergoes secondary infection, necrosis, and an increase in the amount of discharge, which may resemble rice water or bloodwater and have a foul smell. When the tumor spreads upwards and involves the endometrium, the discharge is blocked by the cervical cancer tissue and cannot be discharged, which may lead to hydrometra or pyometra. Patients may experience symptoms such as discomfort, pain, lower abdominal pain, and fever.

　　Pain is a symptom of advanced cervical cancer. The tumor extends along the paracervical tissue, invades the pelvic wall, compresses the surrounding nerves, and is clinically manifested as sciatica or persistent pain in one side of the sacral or iliac region. The compression (erosion) of the ureter by the tumor causes stenosis of the tube, obstruction leading to hydronephrosis, manifested as lumbago or severe pain, which may further develop into renal failure and uremia. The invasion of the lymphatic system leads to lymphatic obstruction, the backflow of lymph fluid is blocked, and symptoms such as edema and pain in the lower limbs may occur.

　　The spread of the tumor forward can invade the bladder, causing symptoms such as frequent urination, urgency, dysuria, even坠感和 hematuria, which are often misdiagnosed as urinary system infection and delay the disease. Severe cases can form vesicovaginal fistula. The tumor can spread backward and invade the rectum, causing symptoms such as abdominal distension,坠感, difficulty in defecation, tenesmus, mucous stools, and hematochezia. Further development may lead to rectovaginal fistula, long-term irregular bleeding, chronic consumption can lead to anemia, accompanied by cachexia, significant weight loss, and in the late stage of the lesion, distant metastasis may occur. The symptoms vary with the site of metastasis, with the most common site being the supraclavicular lymph nodes, where nodules or masses may form. The tumor can infiltrate and spread to distant organs through the blood or lymphatic system, resulting in metastatic foci in corresponding areas.

　　Advanced cervical cancer can spread to distant organs through hematogenous dissemination, the most common sites being the lungs, bones, liver, and brain, etc. Patients with lung metastasis may have symptoms such as chest tightness, chest pain, cough, and blood-tinged sputum. Bone metastasis is common in the lumbar spine, pubic bone, and thoracic spine, causing pain and motor impairment in the corresponding areas. Liver metastasis may cause discomfort in the liver area, abdominal fullness, anorexia, and pain in the liver area.

　　The age range of onset of cervical invasive cancer is wide, with cases occurring between 20 and 90 years old. According to the report of FIGO in 1995, the age distribution of 22,428 cases of invasive cervical cancer: below 40 years old accounted for 26%, 40 to 60 years old accounted for 40%, and above 60 years old accounted for 34%. The incidence rate increased rapidly between 20 and 50 years old, and then decreased, with the peak age of onset around 50 years old. In the past 10 years, the incidence rate of women around 30 to 40 years old has increased significantly. There are certain differences in the incidence rates between different regions due to age changes.

　　1. Prognosis

　　The research on the diagnosis and treatment of prognostic cervical cancer has nearly a century of history, with significant efficacy and generally good prognosis. Early cases can achieve good therapeutic effects through surgery or radiotherapy. The 5-year survival rate of stage I surgery is over 90%, and that of stage II is over 70%. Due to the clinical concentration of middle and late-stage cases, radiotherapy is often used and the efficacy is relatively satisfactory. According to the literature reports from various countries, the overall 5-year survival rate of radiotherapy is 55% to 65%, among which stage I is 70% to 90%, stage II is 60% to 80%, stage III is 40% to 55%, and stage IV is 10% to 20%.

　　Treatment outcomes vary among different units, sometimes significantly, reaching 10% to 20%. The reasons include differences in the interpretation of pre-treatment staging, equipment conditions, technical methods and diagnostic experience, and the selection of cases, such as the selection of early cases and those with good general condition for surgical treatment, those with complications and advanced cases undergoing radiotherapy, resulting in natural differences in survival rates. The FIGO conducted a comprehensive analysis of 96023 cases of cervical cancer in 130+ units in 1985, 1988, and 1991, with a total 5-year survival rate of 55.0% to 53.5%. The percentage of those who died of cervical cancer within 5 years was 34.7% to 35.9%, indicating that the treatment of cervical cancer has not yet reached the desired level. Jacobsen (1991) stated that the treatment of cervical cancer has nearly stagnated over the past 20 years, which seems to be reasonable.

　　2. Factors affecting prognosis

　　There are many factors that affect the prognosis of cervical cancer, such as age of onset, general condition, psychological state, size of the tumor, pathological type, growth pattern, depth of invasion, presence or absence of metastasis, and whether the patient's treatment methods are standardized, such as the selection and scope of surgical indications, radiation therapy methods and doses, chemotherapy drugs and combinations, comprehensive treatment, careful nursing, symptomatic supportive treatment, and psychological comfort. All these are factors affecting prognosis. However, clinical staging, tumor grading, and lymph node metastasis are considered important factors affecting prognosis.

　　1. Cervical exfoliated cytology examination:Currently, it is the most effective screening method for early cervical cancer in China. Since most early cancer patients have no symptoms, it is difficult for doctors to identify the presence of tumors solely by visual observation during clinical examination. Therefore, early cancer is often not detected in time. The cervix is exposed at the top of the vagina, making it easy to observe and collect samples. Therefore, at present, in clinical practice, routine vaginal exfoliated cell examination is performed for all married women during gynecological examination or cancer screening. As a screening method, due to the limitations of the Papanicolaou (Pap) smear test, the false-negative rate can be as high as 25%. The application of the Bethesda TBS system and liquid-based cytology in 1988 greatly improved the positive diagnosis rate of early cervical cancer, reaching over 90%. To improve the accuracy of the smear diagnosis, special attention should be paid to collecting samples from the commonly affected areas of cervical cancer, that is, the junction of flat epithelium and columnar epithelium. Since the junction area of flat and columnar epithelium in elderly women moves upward into the cervical canal, in addition to scraping the cervical-vaginal area, special attention should be paid to collecting samples from the cervical canal to detect cancer within the cervical canal and avoid misdiagnosis. In the past, cervical scraping was often done with a small spatula, later with a double scraper, and now with the liquid-based cytology thin-preparation technique, which has greatly improved the positive diagnostic rate of cytology to a large extent.

　　采取标本时应注意的问题：

　　1、取标本前24h内勿性交，不做阴道检查。

　　2、取标本前3天停止阴道冲洗和阴道上药。

　　3、送检单如患者姓名，年龄，病案号，末次经期，避孕措施，是否经内分泌治疗及物理疗法等，应认真填写。

　　4、以窥器轻轻暴露宫颈，以棉棍轻轻沾取宫颈表面的黏液，避免碰伤出血影响取材。

　　5、将取材器放入宫颈管内，顺时旋转360°，涂片时应朝一个方向均匀涂抹，切忌反复涂抹以至标本制片太厚或重叠，影响诊断。

　　6、如为常规涂片，则待涂片晾干约1～2min后将涂片放入95％酒精里固定。

　　阴道脱落细胞检查异常时，并不一定都是宫颈癌，慢性炎症，重度感染，物理疗法的影响，避孕工具等引起细胞形态改变，以及细胞学制片欠佳，染色过淡及污染等造成的假阳性或异常时，应做进一步检查，如果阴道明显存在炎症或原虫感染，应给予抗炎和对症处理后再取宫颈刮片，必要时定期检查或隔3个月重复细胞学涂片。

　　凡是细胞学检查在巴氏Ⅱ级以上，或是ASCUS（没有决定意义的非典型鳞状细胞），或宫颈上皮内低度瘤变（CINI），或涂片发现癌细胞者（相当于巴氏Ⅳ～V级），都应在阴道镜下多点活检，送病理检查。

　　二、碘试验

　　将浓度为2％的碘溶液直接涂于子宫颈和阴道黏膜上，观察碘染色的情况，不着色处为阳性，以帮助提供活检的部位，此方法在无条件开展阴道镜检查的地方，当宫颈细胞涂片检查异常或临床可疑时，可以借助碘试验帮助发现异常部位。

　　三、鳞状上皮细胞癌抗原（SCC）

　　当肿瘤细胞产生的蛋白进入血液循环时，可以从周边血液测出这些蛋白的含量，作为一种肿瘤标志目前在临床较广泛使用，SCC主要存在于鳞癌成分的宫颈癌中，与临床分期，肿瘤大小及预后有关，许多学者的研究表明：SCC>4ng/ml者淋巴结转移的危险性是SCC

　　四、阴道镜检查

　　阴道镜是一种内窥镜，在强光源下用双目立体放大镜（6～40倍），一般放大20倍左右直接观察宫颈上皮和血管的细微形态变化，凡阴道（宫颈）脱落细胞学巴氏Ⅱ级以上，ASCUS或宫颈上皮内低度瘤变以及临床可疑癌或癌前病变时均应进行阴道镜检查，目的是协助定位活检，提高取材的阳性率，此外亦可用于宫颈癌术后，放疗后的随诊观察。

　　Five, biopsy

　　All the examinations conducted in the clinical diagnosis of cervical cancer are important links, but the biopsy is the most reliable basis for diagnosing cervical cancer. When performing a biopsy, attention should be paid to the following issues:

　　1, Early cervical cancer should be sampled at suspicious or abnormal epithelial and vascular sites under colposcopy to improve the detection rate of biopsy.

　　2, If there are no conditions for colposcopy, perform an iodine test (Schiller test), apply iodine solution to the surface of the cervix. Normal cells contain glycogen and appear black, while abnormal cells do not contain glycogen and do not stain, which is the site for biopsy sampling.

　　3, When a tumor is complicated with infection, sampling should be taken from the fresh tumor tissue or the edge of the lesion to prevent the sampling of necrotic or inflammatory tissue from covering the deep tumor substance.

　　4, Even if the clinical signs and local lesions are very similar to cancer, a biopsy should be performed. Some benign lesions such as chronic cervicitis, cervical tuberculosis, and cervical hemangioma look very similar to tumors, and diagnosis cannot be made solely by naked eye observation. It must be confirmed by biopsy, and if necessary, the tissue inside the cervical canal should be scraped and sent for pathological examination.

　　5, If the cervical tumor is obviously present, but even after multiple biopsies and multiple sampling under colposcopy, the results are still negative, deep sampling or biopsy should be taken to help clarify the diagnosis to avoid missed diagnosis.

　　6, Conization of the cervix: If cancer cells are found multiple times in cervical smear examination or vaginal exfoliated cell cytology examination, but the positive results of the biopsy under colposcopy are negative, and the multiple cervical biopsy is in situ cancer, but the clinical condition cannot exclude invasive cancer, conization of the cervix can be performed. This method can achieve both diagnostic and therapeutic purposes and is considered a win-win method, which is currently more commonly used in the diagnosis and treatment of cervical intraepithelial neoplasia.

　　Six, cystoscopy, rectoscopy, renal scan, renal pelvis angiography, chest X-ray, pelvic image, and in recent years, electronic computerized tomography (CT) and magnetic resonance imaging (MRI) are increasingly used in clinical diagnosis and differential diagnosis (not as the basis for clinical staging). CT scan can assist in understanding the situation of pelvic and para-aortic lymph nodes, while MRI examination can assist in distinguishing the difference between cervical cancer and normal cervix.Some scholars believe that in patients with cervical cancer where the full thickness of the cervix and the lower uterine segment is involved, as shown by clinical MRI, 94% have parametrial invasion, especially in patients with large-volume cervical cancer, who can directly choose simple radiotherapy to avoid misdiagnosis as early cancer and inappropriate treatment. The above auxiliary examinations are very necessary for determining the extent of the lesion, choosing appropriate treatment methods, and improving the treatment rate and judging the prognosis.

　　Attention should be paid to reasonable nutrition in diet, with a variety of foods, including high-protein, vitamin and trace element-rich, low animal fat, easily digestible foods, as well as fresh fruits and vegetables. Avoid eating too much salty and spicy food, and do not eat overheated, cold, expired, or deteriorated food.

　　Pay attention to avoiding staying up late, avoiding unclean sexual life, and avoiding multiple abortions in daily life.

　　Prevention:Early diagnosis, active treatment, and good follow-up.

　　Close and regular follow-up after the treatment of cervical invasive cancer is very important for understanding the changes in the condition, providing further treatment, and judging the prognosis.

　　First, Follow-up Time:Generally, a return visit to the hospital for re-examination is required one month after the end of treatment. If additional radiotherapy is needed, the interval should not be too long. Supplemental treatment is usually given within 2 to 4 weeks. If the condition is stable, a check-up should be performed once every 2 to 3 months within half a year; once every 3 to 6 months within one year; once every half year within two years; and at least once a year thereafter. When the condition changes, the follow-up time should be flexibly controlled.

　　Second, Follow-up Content:

　　1. General Examination:Whether there is enlargement of superficial lymph nodes, abdominal condition, and whether the lower limbs are edematous, etc.

　　2. Postoperative Follow-up:Mainly observe the recovery of the patient's general condition, whether the wound has completely healed, and whether there is lymphedema formation, etc.

　　Third, Rehabilitation Guidance:Rehabilitation treatment includes psychological treatment and physical treatment, which aims to help patients build confidence, face diseases with a positive and optimistic attitude, and engage in appropriate physical exercise, nutrition, and necessary self-care (such as: protecting wounds, maintaining hygiene, and vaginal irrigation after radiotherapy). Proper guidance is provided for the recovery of sexual life after treatment, and the understanding and cooperation of family members are obtained. According to a survey of 316 patients who have survived more than 10 years after radiotherapy at Xi'an Jiaotong University Medical College, 180 cases (57%) of patients have recovered their original labor capacity, and 119 cases (37.7%) of patients have partially recovered their labor capacity, indicating that although radical radiotherapy can cause certain organic and functional changes in women's bodies, most patients (94%) can fully or partially recover their labor capacity. To improve the quality of life, patients who have lost ovarian function and entered menopause prematurely should be relieved of concerns, given targeted treatment, and hormone replacement therapy may be performed under the guidance and observation of a doctor if necessary.