Anal canal cancer is a relatively rare malignant tumor. In 2007, there were 4,650 new cases of anal canal cancer in the United States, accounting for about 1.7% of digestive tract tumors, of which 690 patients died of this disease, and domestic statistics are not available. Compared with the high incidence of gastrointestinal malignancies such as colon cancer and rectal cancer, anal canal cancer is often not taken seriously by clinicians. In the past, clinicians performed radical surgery to treat patients with anal canal cancer, mainly abdominoperineal resection (APR). However, in the past 30 years, the choice of treatment modality for anal canal cancer has been reevaluated, and combined radiotherapy has undoubtedly become the preferred method of anal canal cancer treatment, with surgery usually being used as a rescue operation if the conventional comprehensive treatment is ineffective or the disease recurs. I. Etiology of anal canal cancer Anal canal cancer has been considered to be related to hemorrhoids, anal fistula, anal fissure and other benign diseases, and the research in the last 10 years has shown that, although the above diseases have potential connection with anal canal cancer, they are not directly related to the onset of anal canal cancer, and the occurrence of anal canal cancer is related to a variety of other factors . 1. Human papillomavirus (HPV) infection: Epidemiological and molecular biological studies have shown that HPV infection is the most important causative factor of anal canal cancer.Frisch et al.[3] investigated 386 cases of anal canal cancer patients, and found that the HPV positivity rate of female patients (invasive carcinoma) was as high as 90%, and the positivity rate of male patients (invasive carcinoma) was 63%. 63%.Daling et al. tested 262 anal canal cancer tissues, of which HPV DNA was detectable in 87.9% of the cancer tissues, with no significant difference between male and female rates. Among more than 80 subtypes of HPV, HPVC16 has the closest relationship with anal canal cancer. the exact mechanism of transition from HPV infection to tumorigenesis is not clear, but HPV infection is associated with mild/severe squamous intraepithelial lesions of the anal canal. 2.Immunosuppression Patients applying immunosuppressive drugs for a long time after organ transplantation are at risk of developing squamous cell carcinoma in many parts of the body, and this immunosuppressive state is similar to persistent HIV infection. Some studies showed that the incidence of anal canal cancer increased 100 times after kidney transplantation, and the incidence of anal canal cancer increased in the population using corticosteroid drugs, which was especially significant in the male population with the history of anal intercourse. Sexual behavior Some epidemiological investigations have revealed the relationship between sexual behavior and the incidence of anal canal cancer.Daling et al.[6] used colon cancer as a control in an early investigation (1978~1985).Genital warts or HPV infection or Chlamydia trachomatis were more common in female patients with anal canal cancer, and most male patients with anal canal cancer were unmarried or had a history of anal intercourse. The majority of men with anal canal cancer were consistently unmarried or had a history of anal intercourse. According to the statistics of Danish Cancer Registry, patients with a history of cervical cancer or cervical intraepithelial neoplasia are 3-5 times more likely to develop anal canal cancer than gastric cancer or colon cancer. 4, HIV infection HIV infection is usually accompanied by multiple HPV subtypes, and most patients have HPV-related squamous intraepithelial lesions. The risk of HPV infection in HIV-positive patients is 2 to 6 times higher than that in normal people, regardless of the effect of sexual activity. Although HIV infection increases the chance of HPV infection, it is still unclear whether HIV infection directly leads to the development of anal canal cancer. II. Clinical manifestations and staging of anal canal cancer 1. Clinical manifestations About half of the patients have symptoms of bleeding and are accompanied by pain, but the diagnosis is often delayed because they are thought to be hemorrhoids. Larger tumors may affect the function of anal sphincter, which is manifested as anal incontinence. Clinical examination almost always reveals a mass, most commonly an ulcerated mass with a concave base and elevated margins. Imaging examination is very helpful to understand the invasion of the tumor, regional lymph node metastasis and distant metastasis, the most commonly used is CT examination of the abdomen and pelvis, PET-CT scan can be more sensitive to detect lymph node metastasis, and early detection of lymph node metastasis is of great significance to the staging and selection of radiotherapy dose. Prospective studies show that FDG-PET is a sensitive method for early prediction of treatment effect and prognosis of anal canal cancer. American Joint Committee on Cancer Staging (AJCC) and International Union against Cancer (UICC) have different TNM staging system for anal canal cancer and other intestinal tumors. Unlike the TNM staging of other tumors of the intestinal tract, T in anal canal cancer staging adopts the size of the tumor rather than the depth of tumor infiltration because the size of the tumor tissue of anal canal cancer is an important factor in determining the prognosis. The 5-year survival rate of patients with diameter <2cm (T1~2) is 80%, while the 5-year survival rate of patients with diameter >5cm (T3~4) is less than 20%. C. Treatment of anal canal cancer 1. Combined radiotherapy and chemotherapy Moertel et al. firstly proposed the concept of CRT therapy in 1969 and used it for the treatment of gastrointestinal malignant tumors that could not be surgically resected.In 1974, Nigro et al. of Wayne State University in the U.S.A. [were the first to report on the study of CRT therapy for the treatment of anal canal cancer.The research group conducted adjuvant treatment for 3 cases of anal canal cancer patients before surgery, including continuous infusion of 5-5-hydroxybenzofurane (HFBF). The study team treated three patients with anal canal cancer with adjuvant therapy, including continuous infusion of 5-fluorouracil (5-FU) and mitomycin-C (MMC), in combination with moderate-dose (30Gy) external beam therapy before surgery, and postoperative pathological examination revealed that the tumors had reached pathological complete remission. This encouraging finding made CRT an adjuvant preoperative treatment for anal canal cancer, but in a subsequent study, it was found that after CRT treatment, tumor cells were not found in many postoperative pathological tissues of anal canal cancer, so is there a need for routine radical surgery after CRT treatment? In response to this question, the European Organization for Research and Treatment of Cancer (EORTC) and the United Kingdom Coordinating Committee on Cancer Research (UKCCCR) have developed a new study on the need for radical surgery after CRT treatment. Cancer Research (UKCCCR) conducted two large phase III randomized controlled trials to scientifically evaluate CRT, thus establishing CRT as the treatment of choice for anal canal cancer. Nowadays, the standard regimen of CRT widely accepted by most scholars is continuous radiotherapy (45Gy) combined with 2 cycles of continuous infusion of 5-FU (W1, W5) and MMC (D1, D29). Additional irradiation (5.4Gy to 9.0Gy) is recommended for patients with stage T3 to 4. The National Comprehensive Cancer Network (NCCN) guidelines for the treatment of anal canal cancer, published in 2008, state that for areas of potential microscopic disease, such as the inguinal and pelvic lymph nodes, the recommended radiotherapy dose is 36 Gy to 40 Gy. For patients staged at T1-2, N0, the recommended radiotherapy dose is 45 Gy to 59 Gy. For patients staged at T3-4, N0, or T any but with lymph node metastases, the recommended radiotherapy dose is 55 Gy to 59 Gy. At least 2 cycles of chemotherapy at week 1 and week 5 (5-FU and MMC). 2. Surgery Before the mid-1980s, surgery was considered as the standard treatment for anal canal cancer, and the main surgical procedure was abdominoperineal resection (APR) with or without inguinal lymph node dissection. 5-year survival rate after APR ranged from 40% to 70%, and operative mortality rate was 2.5% to 5%, which was poorer for larger tumors and metastases in lymph nodes. Surgery is not the first choice of treatment for anal canal cancer, but it still plays an important role in the diagnosis and treatment of anal canal cancer. Treatment of adenocarcinoma of anal canal Adenocarcinoma of anal canal is a malignant tumor originated from anal glands, the incidence rate is very low, the incidence rate of male is higher than that of female, and the local recurrence and metastasis rate is higher than that of squamous cell carcinoma of anal canal. Biologically, adenocarcinoma of the anal canal is closer to rectal cancer, and the staging system is the same as that of rectal cancer. The treatment adopts APR surgery combined with postoperative radiotherapy and 5-FU-based chemotherapy, and the 5-year survival rate is about 35%. Treatment of distant metastasis of anal canal cancer After CRT treatment, the rate of distant metastasis of anal canal cancer ranges from 10% to 17%, and the most common metastatic organ is lungs, and the 5-year survival rate after distant metastasis is about 18%. There are fewer studies on the drugs for treating distant metastasis of anal canal cancer, and the drugs usually applied include 5-FU and carboplatin, and drugs such as adriamycin and simastigmine can also be applied for treating other malignant tumors. IV. New progress in the treatment of anal canal cancer 1. Three-dimensional conformal radiation therapy (3D-CRT) The biggest advantage of 3D-CRT is that the distribution shape of high-dose area of radiation therapy is consistent with the shape of lesion (target area) in the three-dimensional direction, which makes the radiotherapy more precise, and the radiotherapy dose can be Vuong et al [14] compared two groups of patients treated with conventional radiotherapy and 3D-CRT, and the local control rate, non-recurrence rate, and overall survival rate of the 3D-CRT group were significantly better than those of the conventional radiotherapy group, and the incidence of toxic reactions was lower. 2.Intensity modulated radiation therapy (IMRT) IMRT, as the mainstream of radiotherapy technology at the beginning of this century, has better conformity and protection of normal organs and tissues than 3D-CRT. This enables the implementation of dose escalation without increasing the amount of normal tissue received and radiotherapy complications, thus obtaining a higher rate of local tumor control. The anal canal is surrounded by numerous important normal tissues, such as the lumbar spine, which stores a large amount of bone marrow, and radiotherapy can also exacerbate chemotherapy-induced myelosuppression, making IMRT ideally suited for the treatment of anal canal cancers.Menkarios et al[15] compared the treatment of anal canal cancer patients with that of 3D-CRT, and IMRT was able to better protect the important tissues, such as the bone marrow of the iliac bone. The preliminary results of a recently published multicenter study also showed the advantages of IMRT combined with chemotherapy in the treatment of anal canal cancer, and a phase II clinical trial (RTOG 0529) currently underway will evaluate IMRT combined with 5-FU and MMC chemotherapy for anal canal cancer. At present, three phase II clinical trials are being conducted in the United Kingdom and the United States, in which the United Kingdom (national research cancer network) and the University of London are cooperating to conduct two studies: ACTII and EXTRA. ACTII, which started in 2001, is the largest clinical trial in anal canal cancer, and its purpose is to evaluate the advantages of CRT (adjuvant chemotherapy) after maintenance chemotherapy (adjuvant chemotherapy). ACTII was initiated in 2001 and is now the largest clinical trial to assess the role of maintenance chemotherapy (adjuvant chemotherapy) after CRT. 600 patients were originally planned to be included, but the sample size has now been expanded to 950, and is expected to be completed in the fall of 2008. EXTRA is a study comparing the CR rate and toxicity of Xeloda in combination with MMC chemotherapy with conventional chemotherapy, and the initial results are more promising. Another anti-tumor drug of great interest is oxaliplatin (Eloxatin), which is used to treat patients with metastatic rectal and colon cancer. A clinical trial conducted at M.D Anderson Cancer Center in the U.S. applied Xeloda plus oxaliplatin chemotherapy combined with radiotherapy to treat patients with anal canal carcinoma (Stage II~IIIB), observing the toxicity response of the patients, the rate of complete remission, the rate of local control and overall survival rate. V. Conclusion In order to achieve the best therapeutic efficacy and the least toxic effect, clinical randomized controlled trials have been carried out continuously, and new antitumor drugs have been applied to the treatment of anal canal cancer successively. Modern molecular biology has provided new ideas for the treatment of anal canal cancer, and strong expression of epidermal growth factor receptor has been observed in anal canal cancer tissues, and the role of molecularly targeted drugs in the treatment of anal canal cancer needs to be verified by clinical trials.