Worldwide, cervical cancer is now the fourth most common female malignancy in both incidence and mortality, following breast, colorectal, and lung cancers, and results in approximately 527 600 new cases and 265 700 deaths annually [1]. It is the second most commonly diagnosed cancer and third most common cause of cancer death among females in low-resource countries. More than 85% of new cases are diagnosed in economically disadvantaged people. Nearly 90% of cervical cancer deaths occur in low-resource regions of the world. The cervix is the lower aspect of the uterus. It is roughly cylindrical in shape, projects through the superior-anterior vaginal wall, and communicates with the vagina through the endocervical canal, which terminates in the external os located at the top of the vagina. Cancer of the cervix may originate from the mucosa of the surface of the cervix or from within the canal. Carcinoma of the uterine cervix grows locally and may extend in continuity to the uterus and paracervical tissues, and pelvic organs. Cervical cancer may spread to regional lymph nodes, and only later metastasize hematogenously to distant structures. Studies on sentinel lymph nodes show that the cervix is drained into the following first echelon nodal stations most commonly: external iliac (43%), obturator (26%) and parametrial (21%), from where they drain to the common iliac nodes. From the common iliac nodes, lymph drainage goes to the para-aortic nodes. The most common sites of distant spread include the para-aortic, mediastinal and supraclavicular nodes, the lungs, liver, and skeleton. FIGO staging is based on clinical examination. The FIGO staging guidelines were most recently updated in 2009 (Table 1) [2]. Stage 0 is no longer included in the FIGO 2009 staging. A thorough pelvic examination is mandatory to provide information for FIGO staging, and this rarely requires anesthesia. When there is doubt as to which stage a particular cancer should be allocated, the earlier stage is mandatory. The following examinations are permitted for the determination of FIGO staging, as indicated by presenting characteristics (see sections below): palpation, inspection, colposcopy, endocervical curettage, hysteroscopy, cystoscopy, proctoscopy, intravenous pyelography, ultrasound of the renal tract, and X-ray examination of the lungs and skeleton. Blood tests should include full blood count, and renal and liver functions. Syphilis and HIV serology need to be considered, based on discussion with the patient about risk factors. The diagnosis of both Stage IA1 and IA2 should be based on microscopic examination of removed tissue, preferably a cone biopsy, which must include the entire lesion. The depth of invasion should not be greater than 5 mm taken from the base of the epithelium, either surface or glandular, from which it originates. The second dimension, the horizontal spread, must not exceed 7 mm. Vascular space involvement, either venous or lymphatic, should not alter the staging, but should be specifically recorded because it may affect treatment decisions. Macroscopically obvious lesions, and those with larger dimensions, should be staged as IB. It is impossible to clinically determine if a cancer of the cervix has extended to the corpus. Extension to the corpus should therefore be disregarded for staging purposes. The diagnosis of Stage IA1 or IA2 disease can only be made on the basis of a cone biopsy with negative margins, or on a trachelectomy or hysterectomy specimen. If the margins of the cone biopsy are positive for cervical intraepithelial neoplasia (CIN) III or invasive cancer, a second cone biopsy should be performed or the patient treated as for Stage IB1 disease [3]. Visible lesions require a biopsy to confirm a diagnosis of cervical carcinoma. A patient with a growth apparently fixed to the pelvic wall by a short and indurated, but not nodular, parametrium should be allotted to Stage IIB. Stage III should be defined for cases where the parametrium is nodular to the pelvic wall or if the growth itself extends to the pelvic wall. The presence of hydronephrosis or non-functioning kidney(s) resulting from obstruction of the ureter(s) by cancer also permits a case to be allotted to Stage III. In cases of grossly invasive disease, a chest X-ray, and evaluation of hydronephrosis (with renal ultrasound, intravenous pyelography, CT, or MRI) are mandatory. The bladder and rectum are evaluated by cystoscopy and sigmoidoscopy only if the patient is clinically symptomatic. Cystoscopy is also recommended in cases of endocervical growth with a barrel-shaped surface and in cases where the growth has extended to the anterior vaginal wall. Suspected bladder or rectal involvement should be confirmed by biopsy and histologic evidence. The presence of bullous edema, as such, should not permit a case to be allotted to Stage IV. Imaging evaluation may be of additional benefit to clinical examination in practice areas where resources allow. Imaging may allow for identification of additional prognostic factors and help direct selection of therapy. MRI provides the best radiologic assessment of primary tumors greater than 10 mm, but is not mandatory [4–8]. Level of Evidence B CT and/or MRI and/or positron emission tomography (PET) may provide information on nodal status or systemic spread, but are not mandatory. Compared with CT and MRI, PET-CT is a more accurate imaging method for detecting nodal metastasis that are greater than 10 mm [5,9–12]. Isolated and unexpected areas of PET enhancement should be further investigated with tissue diagnosis, if possible, to confirm or exclude the presence of distant metastatic disease [11,13,14]. Level of Evidence B Compared with radiologic evaluation, surgical node dissection is more accurate for assessment of para-aortic nodal disease [15,16]. In patients with advanced disease, laparoscopic staging of para-aortic lymph nodes may be considered to allow treatment according to extent of disease [17]. No impact on survival has been demonstrated; however, surgical exclusion of para-aortic lymph node involvement portends a better prognosis than radiographic exclusion alone [18]. Level of Evidence B In a review of 22 articles that evaluated the safety and impact of pre-treatment surgical para-aortic lymph node staging (PALNS), para-aortic lymph node metastases were found in 18% (range, 8%−42%) of patients with cervical cancer Stage IB-IVA [19]. The mean complication rate of PALNS was 9% (range, 4%−24%), the most common complication being lymphocysts. PET-CT appears to be the most accurate imaging method, with false-negative results in 4%−15% of cases. Positive para-aortic nodes have been identified in up to 35% of Stage IIB and 20% of Stage III tumors [19]. Knowing the status of para-aortic nodes may provide prognostic information as well as guide the extent of adjuvant or primary radiation. It is, however, controversial and is not recommended as a routine practice, particularly in resource-restricted environments and in women with advanced disease associated with constitutional symptoms. In cases treated by surgical procedures, the pathologist's findings in the removed tissues can be the basis for accurate statements on the extent of disease. The findings should not be allowed to change the clinical staging, but should be recorded in the manner described for the pathologic staging of disease. The TNM nomenclature is appropriate for this purpose [20]. Unlike FIGO staging criteria, TNM staging accounts for node positivity; however, the FIGO and TNM classifications are otherwise virtually identical in describing the anatomical extent of disease. Clinical staging is essential to select and evaluate therapy, while the pathological stage provides the most precise data from which to estimate prognosis and calculate end results. Infrequently, hysterectomy may be carried out in the presence of unsuspected invasive cervical carcinoma. Such cases cannot be clinically staged or included in therapeutic statistics, but it is desirable that they be reported separately. If considered appropriate, some of these patients may be offered repeat laparotomy with full parametrectomy and pelvic lymphadenectomy to allow potentially curative surgery and/or determine the need for adjuvant chemoradiation [21]. Staging is determined at the time of the primary diagnosis and cannot be altered, even at recurrence. Only if the rules for clinical staging are strictly observed is it possible to compare results among clinics and by differing modes of therapy. Squamous cell carcinoma (keratinizing; non-keratinizing; verrucous). Endometrioid adenocarcinoma. Clear cell adenocarcinoma. Adenosquamous carcinoma. Adenoid cystic carcinoma. Small cell carcinoma. Undifferentiated carcinoma. GX: Grade cannot be assessed. G1: Well differentiated. G2: Moderately differentiated. G3: Poorly or undifferentiated. When surgery is the primary treatment, the histologic findings permit the case to have pathologic staging, as described above. In this situation, the TNM nomenclature may be used. Primary prevention of cervical cancer through HPV vaccination of girls, and secondary prevention through the detection of cervical cancer precursors by various screening methods and their appropriate treatment, are both known to be effective preventive measures. Details on cervical cancer screening can be accessed via the FIGO website (www.figo.org). Conization is the treatment of choice for this stage. If the patient has completed childbearing, hysterectomy (abdominal, vaginal, or laparoscopic) may be considered [22]. Follow-up with Pap smears every 3 months for 2 years, and then every 6 months for a further 3 years should be performed. If follow-up is normal at 5 years, the screening schedule may be completed according to the recommendations in each country [23,24]. Level of Evidence C Since lymph nodes may be involved in this stage, lymphadenectomy is necessary [25,26]. The recommended treatment is type 2 radical hysterectomy (ligation of the uterine artery where it crosses the ureter, although a vaginal cuff is not necessary) with pelvic lymphadenectomy. If fertility is desired, options are: (1) cervical conization with extraperitoneal or laparoscopic pelvic lymphadenectomy; or (2) radical abdominal, vaginal, or endoscopic trachelectomy with pelvic lymphadenectomy performed according to the surgical approach [27,28]. Follow-up with Pap smears every 3 months for 2 years, and then every 6 months for a further 3 years should be performed. If follow-up is normal at 5 years, the screening schedule may be completed according to the recommendations in each country [23,24]. Level of Evidence C Concurrent platinum-based chemoradiation is the most indicated treatment for this stage although neoadjuvant chemotherapy may play a role in selected settings [29]. The treatment approach should be decided based on the availability of resources, and tumor- and patient-related factors. Surgical treatment may be indicated in Stage IB1–IIA1 disease: modified radical or radical (abdominal or endoscopic) hysterectomy with pelvic lymphadenectomy [30–32]. Level of Evidence B Primary pelvic exenteration may be considered for Stage IVA disease without extension to the pelvic sidewall or extra-pelvic disease [33–46]. Level of Evidence C Identification of sentinel lymph nodes can be performed with dual labeling using blue dye and radiocolloid [47–49]. These procedures may be considered in early stage cervical cancer, Stage IA and IB1 [50–52]. If lymphovascular space invasion is present, pelvic lymphadenectomy needs to be considered. Level of Evidence C Sentinel lymph node assessment of pelvic lymph nodes should not be utilized in advanced disease [53]. Stages IA2–IB1 with tumor size of less than 2 cm, cervical stromal invasion of less than 50%, and node negative on MR/CT imaging have been considered as low risk. Simple hysterectomy or trachelectomy, with either pelvic lymphadenectomy or sentinel lymph node assessment, have been considered as adequate surgical treatment for low-risk cases [54,55]. Level of Evidence D The risk of recurrence after radical surgery is increased in the presence of positive nodes, positive parametria, or positive surgical margins. Adjuvant concurrent chemoradiation (cisplatin with or without 5-fluorouracil) improves overall survival, progression-free survival, and both local and distant recurrences compared with pelvic irradiation alone in such patients [42]. Level of Evidence B Risk of pelvic recurrence is also increased in those with uninvolved nodes but with primary associated risk factors: tumor size greater than 4 cm, capillary-like space (CLS) involvement, and outer one-third invasion of the cervical stroma [43,44]. Adjuvant whole pelvic chemo-irradiation reduces the local failure rate and improves progression-free survival compared with patients treated with surgery alone [43]. Level of Evidence B Adjuvant radiation therapy with and without chemotherapy may be particularly beneficial for patients with adenocarcinoma or adenosquamous histology, given the relatively higher rates of distant failure [42,43]. Level of Evidence C Patients with positive common iliac or para-aortic nodes may be treated by extended field radiation [56,57], with or without chemotherapy. Level of Evidence C Intensity modulated radiation therapy has been explored in the postoperative setting. A prospective multi-institutional study has shown acceptable toxicities with this approach and a randomized trial (TIME-C) is underway comparing intensity-modulated radiation therapy (IMRT) with standard field-based radiation therapy in postoperative cervical and endometrial cancer [58,59]. Although there is currently insufficient evidence at the present time to recommend IMRT as a standard of care, many centers have shifted to using this technique in postoperative cervical and endometrial cancer treatment. The theoretical rationale for the use of neoadjuvant chemotherapy (NACT) includes the induction of tumor shrinkage to facilitate radical excision, and a possible improvement in outcomes over surgery alone. There is also a possibility of NACT sterilizing nodes and parametria, thereby reducing risk factors for adjuvant therapy after surgery; however, the efficacy of neoadjuvant therapy in this situation is not known. A meta-analysis of randomized trials of neoadjuvant platinum-based chemotherapy prior to definitive surgery shows that patients treated with NACT have better survival outcomes than those treated with primary radiation given at a relatively low No randomized data compare the results of NACT by surgery with concurrent The for and of Cancer is currently a 3 study comparing NACT and surgery with definitive chemoradiation in patients with FIGO Stages or IIB cervical NACT by surgery is commonly in some but role is as a review of no benefit of over surgery adjuvant therapy pathologic defined as disease with less than 3 mm of stromal invasion in the surgical is the of from local recurrence for patients treated with NACT and surgery A chemotherapy of and has higher rates than and for Stage although not for Stage IIB A on overall survival was not although this study was for overall survival outcomes after NACT should of radical hysterectomy and pelvic lymphadenectomy. patients randomized to either were to with radical surgery after chemotherapy or additional adjuvant therapy after surgery (26%) NACT surgery should be considered in patients with larger tumors or adenocarcinoma to lower Stage IIB and higher should be with definitive chemoradiation therapy. NACT the pathologic findings at the time of evaluation of for adjuvant with or without adjuvant chemotherapy. for adjuvant therapy after primary surgery are in the of NACT Level of Evidence C is the standard of for patients with and IVA disease. concurrent chemoradiation therapy includes external radiation and Level of Evidence A radiation treatment of cervical carcinoma is external pelvic irradiation of external radiation are in radiation are in A full of radiation in cervical cancer treatment is included in the radiation therapy included in the FIGO Cancer of is essential for In trial patients with treatment of greater than higher rates of pelvic compared with women treatment in less than It is recommended that external and be completed within Concurrent chemoradiation a overall survival benefit compared with the radiation with a meta-analysis of trials a survival of [29]. Concurrent also local and distant and Level of Evidence A A of with appropriate for is a commonly concurrent chemotherapy and is effective and less than and in a schedule external therapy patients are to are acceptable on the associated with concurrent chemotherapy and extended field irradiation are Although randomized of included patients with Stage and given the of the survival concurrent chemotherapy with a platinum-based is recommended for patient considered for radical if the patient is adjuvant chemotherapy after concurrent is being explored in randomized trial A randomized study possible benefit in progression-free and overall survival with additional but with more present there is insufficient evidence to recommend additional adjuvant chemotherapy as a standard of essential of radical or tumors may be with external radiation alone if and/or are not prognostic factors for of include lower stage, cell histology, and In where is not external is a to local A radiation of can provide local rates of with a time to recurrence of years A review of trials for follow-up of women after treatment for cervical cancer found the time to recurrence after treatment from months after primary treatment follow-up has not been and clinical practice is recommendations include patients about and clinical examination at routine follow-up to treatment and as well as to for disease. Level of Evidence D tests include chest X-ray, ultrasound, CT and intravenous recurrences are potentially clinical follow-up in the years after treatment may be imaging is not such as involved pelvic lymph nodes, may imaging of the to for potentially of disease. In the disease was using chest X-ray CT and vaginal vaginal not the detection of early disease recurrence. Patients should to screening after 5 years of survival with distant metastatic disease is reported in about of cases There has been no randomized of chemotherapy to best for Stage cervical carcinoma. have evaluated the impact of systemic therapy on and There is some evidence that concurrent chemoradiation may have better than systemic chemotherapy and of and have been reported in patients with positive para-aortic and supraclavicular lymph nodes Level of evidence D A should that the of survival with distant metastatic disease is approximately 7 has been the standard chemotherapy in the of distant metastatic disease low rates to alone after concurrent evidence the use of over although with in may be with or has also been in these cases. In a the of in a of to chemotherapy with a of either or was evaluated increased the overall survival months for in a and higher rates as compared with chemotherapy was associated with increased incidence of of 2 or higher of 3 or higher and of 3 or higher systemic therapy may be considered for patients with status of (Table of in clinical trials should be considered, particularly for patients have within months treatment with radiation therapy is indicated to sites of involvement in patients with metastatic disease. of with radiation can be for from para-aortic or supraclavicular nodes, metastases and associated with In of the short of patients with metastatic cervical cancer, should be given via larger over of time than radical of treatment. There are no data to for tissue commonly include in and in 10 Patients with cervical cancer may a of and should be on associated with advanced cervical cancer can obstruction renal and Patients may benefit from a of clinical to these as well as and for patients and their to is within low-resource and is aspect of may be para-aortic, or a The risk of both pelvic and distant failure with the of disease The of recurrences occur within 3 years of diagnosis, and the prognosis is with most patients as a of disease should be based on the status of the the of recurrence and/or the extent of metastatic disease, and prior treatment patients with local disease or distant metastatic disease, the of therapy is and best is the recommended patients with status and metastatic disease, a trial of systemic therapy may be the with to rate and progression-free survival recurrence that is not with surgery or has a to systemic chemotherapy. patients with locally disease after definitive therapy or are potentially prognostic factors include pelvic recurrence with no sidewall disease, a and size of the recurrence less than 3 in in the following primary surgery may be treated by either radical chemoradiation or pelvic irradiation with or without concurrent may in survival rates of with pelvic failure after primary surgery The extent of disease and involvement of pelvic lymph nodes are prognostic factors for survival Level of Evidence C The radiation and should be to the extent of in should be to areas to be involved with microscopic disease, and a of up to to the tumor using field Concurrent chemotherapy with either and/or may exenteration may be a treatment in selected patients have recurrence after radiation. for exenteration after surgery or pelvic radiation are patients without evidence of or pelvic spread, and have a space the pelvic sidewall Level of Evidence C to the of use is to those with curative and requires patient selection the associated and of recurrence with a pathologic by biopsy is essential prior to with A is the most to determine sites of distant disease, and if possible, should be performed prior to exenteration assessment and the and to and sites must be prior to surgery selection of patients may a survival with pelvic exenteration in the of and of less than the para-aortic lymph nodes are the most common of disease. survival with or can be in approximately of patients with para-aortic nodal recurrence Patients with low recurrences that occur greater than months from treatment have better outcomes Level of Evidence C cervical cancer may be found the pathological evaluation of the of a hysterectomy for apparently survival is lower in cases of tumor disease When this a if or a pelvic and CT or MRI and chest imaging should be to the extent of disease. The treatment should be based on the histologic and the radiologic radiation (with or without concurrent and vaginal should be considered Level of Evidence C A with the involvement of and is recommended to a therapeutic should be with the patient preferably and must be In the of cervical cancer in women the as in are treated without with either surgery or From the second surgery and chemotherapy can be in selected cases while the Level of Evidence C If the diagnosis is made after treatment appears to be for Stages IA2 and with no of prognosis compared with of and radical hysterectomy is a is and not later than of Level of Evidence C more advanced disease, it is not known treatment affect If a treatment is in women with locally advanced disease, neoadjuvant chemotherapy may be considered in to disease has a from for has through from and has no of The is not for the or of information by the than should be to the for the