Cervical cancer is a common malignant tumor in women worldwide. In 2012, there were an estimated 530,000 new cases worldwide and about 270,000 deaths from cervical cancer. There are about 150,000 new cases of cervical cancer in my country every year. Cervical cancer is dominated by squamous cell carcinoma. The incidence of adenocarcinoma is significantly lower than that of squamous cell carcinoma. However, in recent years, the incidence of adenocarcinoma has been increasing, and the proportion of cervical cancer has risen to 10%-20%, especially in 35-year-olds. The number of young patients below has increased significantly. In 2015, the global incidence of cervical adenocarcinoma was estimated at 56,805 cases. The average age of onset of adenocarcinoma is 44 to 54 years old, and this data is not significantly different from that of squamous cell carcinoma. Previous studies have confirmed that adenocarcinoma has a similar pathogenesis to squamous cell carcinoma. However, unlike the almost 100% HPV infection rate in cervical squamous cell carcinoma, 80% of adenocarcinomas are related to HPV, and 20% of adenocarcinomas are not related to HPV. Similar to squamous cell carcinoma, HPV16 and HPV18 are also the most common subtypes of adenocarcinoma. In addition, HPV45 is more closely related to adenocarcinoma than squamous cell carcinoma. HPV-positive adenocarcinoma patients are common in young patients, and FIGO staging is common in early stages. In contrast, HPV-negative adenocarcinoma is common in older patients, and FIGO staging is common in advanced stages.

　　1. Clinical features

　　Similar to squamous cell carcinoma, early cervical adenocarcinoma often has no symptoms and signs. Patients with cervical adenocarcinoma are easily missed due to the normal appearance of the cervix. As the disease progresses, the following symptoms and signs may appear.

　　1.1 Symptoms

　　1.1.1 Vaginal bleeding

　　The early stage of the disease often manifests as contact bleeding, which usually occurs after sex; as the disease progresses, it may manifest as irregular vaginal bleeding. The amount of bleeding varies according to the extent of the lesion. For example, the invasion of the large interstitial blood vessels by the cancer can cause hemorrhage. Exogenous adenocarcinoma generally bleeds earlier, and endogenous adenocarcinoma bleeds later.

　　1.1.2 Vaginal drainage

　　Adenocarcinoma patients have a higher rate of vaginal discharge than squamous cell carcinoma, and some patients only see this as the only symptom in the early stage. The discharged liquid is white or bloody, as thin as water, in a large amount, with or without fishy smell. Such as adenocarcinoma tissue necrosis with infection, a large number of purulent foul-smelling vaginal discharge can be seen.

　　1.1.3 Late symptoms

　　According to the different accumulation range of the lesions, it shows different symptoms. For example, when the bladder and ureter are accumulated, symptoms such as frequent urination, ureteral obstruction, and hydronephrosis may occur; when the rectum and nerves are accumulated, symptoms such as constipation, blood in the stool, swelling of the lower limbs, and pain may occur. In addition, it can manifest as symptoms of systemic failure such as cachexia and anemia.

　　1.2 Signs

　　Micro-invasive adenocarcinoma may have no obvious lesions by naked eyes, and the cervix is smooth or only shows cervical erosion. More than 50% of cervical adenocarcinomas grow exogenously. As the disease progresses, new cauliflower-like and polyp-like organisms can be seen in the cervix of exogenous adenocarcinoma, which is brittle in texture and has obvious blood contact. A small number of cases showed endogenous growth, manifested as cervical hypertrophy, with diffuse thickening of the cervical canal wall as prominent manifestations. Advanced adenocarcinoma often presents as ulcers or hollows. If the vagina is affected, it can be seen that the vaginal vault disappears, and the vaginal wall sees new organisms, which are hard and bloody. If the uterus is involved, the triad examination can palpate the periuterine thickening, hardness, shortening, and even the formation of frozen pelvis.

　　2. Early diagnosis

　　The adenoepithelial neoplasia of the cervix also has a series of evolution processes. Because glandular epithelial lesions are relatively rare, and the special structure of their tissues, the evaluation of precancerous lesions is more difficult than that of squamous epithelium. In addition, some terminology and histopathological standards have not yet been unified, making the diagnosis of cervical adenocarcinoma and precancerous lesions more difficult than squamous cell carcinoma. The early diagnosis of cervical adenocarcinoma still adopts the “three-step” method of cervical cancer diagnosis recommended by WHO, namely cervical cytology→colposcopy biopsy→pathological diagnosis. If new cervical organisms are visible to the naked eye, a cervical biopsy is performed directly to confirm the diagnosis. After the diagnosis of cervical adenocarcinoma by paraffin pathology section, at least two experienced gynecological oncologists with senior professional titles should carefully examine the body to determine the clinical stage. Depending on the specific situation, CT, MRI and other imaging examinations can be selected to assist in the evaluation of the condition。

　　2.1 Cervical cytology

　　One of the main methods of cervical adenocarcinoma screening. The diagnosis results are classified according to the TBS system. If it suggests abnormal glandular cells, including atypical glandular epithelial cells, atypical glandular epithelial cells tending to become neoplastic, adenocarcinoma in situ, and adenocarcinoma, referral to colposcopy is required. However, compared with cervical squamous cell carcinoma, cytology is of lower diagnostic value in adenocarcinoma. Because cytology sampling may be difficult to collect cell specimens for glandular diseases. According to different studies, only about 41% to 70% of patients with adenocarcinoma have cytological tests that indicate the presence of atypical glandular cells. Because cervical glands are mainly distributed in the cervical canal and transition zone, and glandular epithelial lesions are relatively rare than squamous epithelium, the experience of cytological diagnosis is not as good as that of squamous cell lesions, so the sensitivity is restricted by both sampling and interpretation, leading to the screening of adenoma Check effectiveness is relatively low. Studies have shown that the cytological examination before cervical conization can screen out adenocarcinoma in situ is only 38%-50%.

　　2.2 Human papillomavirus (HPV) detection

　　Currently one of the main methods of cervical cancer screening, the latest cervical cancer screening guidelines still recommend that HPV testing be combined with cervical cytology. The recommended age for the first HPV test is 30. HPV16 and 18 are closely related to the onset of cervical adenocarcinoma. If the HPV test result shows positive type 16 and (or) 18, it is recommended to directly refer to colposcopy.

　　2.3 Colposcopy and cervical biopsy

　　It is recommended to refer to colposcopy for patients with atypical glandular cells and more severe cytology. Common colposcopy abnormalities include villi-like changes, flaky changes, and thick white epithelial changes in the cervical transformation zone. Select suspicious lesion areas for cervical biopsy. If there is no suspicious area, fixed-point four-quadrant biopsy can be performed at 3, 6, 9, 12 o'clock in the transition zone. However, some adenoid tumors occur closer to the inner mouth of the cervical canal, and it is recommended to perform cervical curettage at the same time. Because colposcopy and biopsy are negative, tumor gonadal cell lesions cannot be ruled out. For cases where cytology suggests abnormal glandular cells but the biopsy shows normal, the biopsy should be repeated, and the cytology and HPV should be closely followed up for 3 to 6 months.

　　2.4 Cervical conization

　　Cervical cytology is positive for many times, but cervical biopsy is negative; or biopsy reveals cervical adenocarcinoma in situ, and it is necessary to confirm whether there is invasive cancer, cervical conization should be performed for pathological examination. Cervical conization can choose cold knife conization or cervical circular electrosurgical resection (LEEP).

　　2.5 Pathological diagnosis

　　The precancerous lesions of cervical adenocarcinoma mainly include two major categories, cervical gland dysplasia and adenocarcinoma in situ. At present, for the diagnosis of cervical gland dysplasia, histological diagnostic criteria are not uniform. In view of this, it is generally recommended to perform p16 and Ki67 immunohistochemical staining for this type of lesion to better provide reference for clinical treatment. For adenocarcinoma in situ, in the 2003 WHO classification, this nomenclature is clearly defined: the normal cervical gland is partially or completely replaced by malignant epithelial cells. Most adenocarcinomas in situ are focal, but about 13% to 17% of cases are diffuse or multifocal, and a few cases even show skipping multifocal lesions. The 2003 version of the WHO classification divides cervical invasive adenocarcinoma into typical cervical adenocarcinoma, which is the most common type of cervical adenocarcinoma, accounting for 70% to 80% of cervical adenocarcinoma. Other pathological classifications include mucinous adenocarcinoma, endometrioid adenocarcinoma, clear cell adenocarcinoma, serous adenocarcinoma, slightly biased adenocarcinoma, and adenosquamous carcinoma.

　　3. Facing challenges

　　Because the precancerous lesions of cervical adenocarcinoma are relatively rare, the following challenges exist in the early clinical diagnosis of invasive cervical adenocarcinoma:

　　①The morphological characteristics of adenocarcinoma in situ are not yet clear;

　　②The lesions often involve the cervical canal, making it difficult to obtain materials;

　　③Invasive cervical adenocarcinoma often develops from very small in situ adenocarcinoma lesions;

　　④The histological characteristics of adenocarcinoma in situ are diverse, and the cytological and colposcopy characteristics have not yet formed a broad consensus. Therefore, the low sensitivity of cytology screening, the lack of experience of colposcopy, atypical colposcopy changes, the size and location of the lesions and other factors will affect the early diagnosis of cervical adenocarcinoma and precancerous lesions.