History

Fact Explanation
Asymptomatic patients detected incidentally Majority of patients are diagnosed incidentally as part routine cervical smear assessment. Further investigation of patients with abnormal smear cytology may lead to diagnosis of cervical carcinoma. Cervical carcinoma limited to the basement membrane is classified as cervical intraepithelial neoplasia (CIN). Majority of patients with CIN are asymptomatic.[1]
Post menopausal bleeding Cervical carcinoma are usually friable vascular masses which give rise to bleeding manifestations. Pre-menopausal women may present with irregular vaginal bleeding/ intermenstrual bleeding.
Post-coital bleeding The physical trauma associated with sexual intercourse may cause bleeding from the tumor mass.
Vaginal discharge The vaginal discharge may be offensive and blood stained.
Pelvic pain Due to tumor extension into surrounding pelvic structures. Tumor spread to the spinal cord may lead to worsening of the pain.
Fatigue/ malaise/ weakness/ exertional dyspnea Anemia may develop due to chronic vaginal bleeding.
Symptoms of advanced disease Cervical carcinoma usually spreads locally and metastasizes via the lymphatics channels. Local spread may lead to vesicovaginal fistulae formation and may present with incontinence. Spread to pelvic lymph nodes may result in lower limb edema.
Local spread Tumor spread may obstruct the nearby ureters leading to renal failure. Spread to the bladder may result in haematuria and bowel involvement may result in rectal bleeding.
Regional spread Regional spread may lead to vesicovaginal fistulae formation and may present with incontinence. Spread to pelvic lymph nodes may result in lower limb edema.
Distant spread Spread to the liver, bone and lung is rare. Right hypochindrial pain and jaundice may develop when metastasis occurs to the liver. Chronic dyspnea may be a presenting symptoms of pleural effusion. Localized excruciating bone pain of the spine and long bones is due to metastasis to the bones.
Risk factors for cervical carcinoma Cervical carcinoma is strongly associated with Human papilloma virus infection.[2] HPV type 16,18,31 and 33 have high oncogenic properties. Multiple sexual partners, early age of onset of sexual activity, male partner with multiple sexual partners, commercial sex workers are risk factors for this malignancy. Smoking, immunodeficiency and poor hygiene also increase the risk of both pre-invasive and invasive disease.[3]
References
  1. BUCKLEY CH, BUTLER EB, FOX H. Cervical intraepithelial neoplasia. J Clin Pathol, 1982, 35, 1-13.
  2. SCHIFFMAN M, CASTLE PE, JERONIMO J, RODRIGUEZ AC, WACHOLDER S. Human papillomavirus and cervical cancer. Lancet [online] 2007 Sep 8, 370(9590):890-907 [viewed 31 July 2014] Available from: doi:10.1016/S0140-6736(07)61416-0
  3. PLUMMER M, HERRERO R, FRANCESCHI S, MEIJER CJ, SNIJDERS P, BOSCH FX, DE SANJOSé S, MUñOZ N, IARC MULTI-CENTRE CERVICAL CANCER STUDY GROUP. Smoking and cervical cancer: pooled analysis of the IARC multi-centric case--control study. Cancer Causes Control [online] 2003 Nov, 14(9):805-14 [viewed 31 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/14682438

Examination

Fact Explanation
Physical examination may be normal Clinical signs are minimal in early disease and in malignancy limited to the endocervical canal.
Speculum examination Discoloration, erosion and ulceration may be seen on the cervix. In advanced disease the tumor may appear as a macroscopic mass.
Vaginal examination The ulcerated, eroded cervix may be felt. Masses arising from the cervix may be felt. Pelvic masses may be detected if the disease has spread locally. Contact bleeding may be noted when withdrawing the fingers.
Rectovaginal examination Rectovaginal examination, carried out under anesthesia can determine tumor size, fixity and tumor spread.[1] The tumor can be clinically staged by rectavaginal examination. Palpate the upper vagina for tumor spread. Examine the parametrial area to detect spread to the lateral pelvic walls. Stage 2 and stage 3 disease can be differentiated by this maneuver.
Examine for local spread Examine for pelvic masses during vaginal examination.
Distant spread - Respiratory examination : signs of pleural effusion Due to metastasis to the lungs.
Distant spread - Abdominal examination : Hepatomegaly Hepatomegaly may be present in advance disease. The enlarged liver has an irregular surface and margin and is hard in consistency.
References
  1. PETIGNAT P., ROY M.. Diagnosis and management of cervical cancer. BMJ [online] 2007 October, 335(7623):765-768 [viewed 31 July 2014] Available from: doi:10.1136/bmj.39337.615197.80

Differential Diagnoses

Fact Explanation
Endometrial carcinoma Endometrial carcinoma is a important cause of postmenopausal bleeding. The disease characteristically presents in the sixth and seventh decade. The mean age of presentation is 54 years. The presenting symptoms are postmenopausal bleeding, post-coital bleeding, intermenstual bleeding, vaginal discharge and pelvic pain. Physical examination is usually normal except for an enlarged uterus.The disease usually presents at an early stage. Diagnosis is by transvaginal ultrasound scan, hysteroscopy and endometrial sampling.[1]
Atrophic vaginitis Atrophy of the female genitalia in the postmenopausal period is due to decreased estrogen level within the body. This results in atrophy of the fibrous support structures of the cervix, vagina and vulva. It may be present in about 50% of postmenopausal women. Vulvovaginal atrophy presents with dryness and soreness of the vagina which is more prone to trauma and infection. Urinary symptoms such as dysuria, frequency and incontinence may be seen. Atrophy of the vulva and vaginal walls is evident at physical examination. The mucosa of the vagina appears dry, pale and may have petechiae. Vaginal rugae are absent and the cervix may appear reddened. Diagnosis of atrophic vaginitis is clinical. The vagina pH is more than 4.6. Treatment consists of topical estrogen therapy.[2]
Cervical polyp Cervical polyps are abnormal extensions from the cervical epithelium. The aetiology is completely not understood. Chronic infection, chronic inflammation and hormonal changes are linked with cervical polyps. Majority of patients are asymptomatic. Patient may present with abnormal vaginal bleeding. When infected and inflamed the patient may present with purulent vaginal discharge. The diagnosis can be made by visualization during speculum examination. Polypectomy is usually an out-patient procedure where the polyp is removed either manually or by forceps. Endometrial sampling by dilatation and curettage can be carried out simultaneously to exclude the possibility of malignancy.[3]
References
  1. SASO S., CHATTERJEE J., GEORGIOU E., DITRI A. M., SMITH J. R., GHAEM-MAGHAMI S.. Endometrial cancer. BMJ [online] December, 343(jul06 2):d3954-d3954 [viewed 01 August 2014] Available from: doi:10.1136/bmj.d3954
  2. MAC BRIDE MB, RHODES DJ, SHUSTER LT. Vulvovaginal Atrophy Mayo Clin Proc [online] 2010 Jan, 85(1):87-94 [viewed 01 August 2014] Available from: doi:10.4065/mcp.2009.0413
  3. GOLAN A, BER A, WOLMAN I, DAVID MP. Cervical polyp: evaluation of current treatment. Gynecol Obstet Invest [online] 1994, 37(1):56-8 [viewed 01 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/8125411

Investigations - for Diagnosis

Fact Explanation
Cervical biopsy A biopsy is essential to confirm the diagnosis of malignancy and to determine the tumor type. Biopsy can be attempted during coloposcopic examination or as an in-patient procedure. Loop diathermy biopsy (LLETZ), punch biopsy and cone biopsy are two commonly used varieties. LLETZ is performed under local anesthesia where the a diathermy loop is used to Cervical biopsy may also be a therapeutic measure for pre-invasive tumors.[1]
References
  1. STASINOU SM, VALASOULIS G, KYRGIOU M, MALAMOU-MITSI V, BILIRAKIS E, PAPPA L, DELIGEOROGLOU E, NASIOUTZIKI M, FOUNTA C, DAPONTE A, KOLIOPOULOS G, LOUFOPOULOS A, KARAKITSOS P, PARASKEVAIDIS E. Large loop excision of the transformation zone and cervical intraepithelial neoplasia: a 22-year experience. Anticancer Res [online] 2012 Sep, 32(9):4141-5 [viewed 31 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/2299337

Investigations - Fitness for Management

Fact Explanation
Full blood count Chronic blood loss may cause iron deficiency anemia
Renal function tests In preparation for surgery.
Blood grouping and save In preparation for surgery.
References

Investigations - Screening/Staging

Fact Explanation
Staging of the malignancy Staging of the disease is important to decide on the management plan and to determine the prognosis of the patient. Cervical carcinoma is staged according to the staging system of the International federation of Obstetricians and Gynaecologists (FIGO). Stage 1– Carcinoma confined to the cervix, Stage 2 – Carcinoma extending beyond the cervix and involving the vagina or parametrium. Stage 3 – Carcinoma involving the lower third of the vagina and/ or extending to the pelvic sidewalls. Stage 4 – Carcinoma involving the mucosa of the bladder/ rectum or spread to distant organs.[1]
Clinical staging Rectovaginal examination under anesthesia can help determine tumor spread. Assess tumor spread along the vagina. Examine the lateral parametrial spaces for tumor spread. Tumor spread up to the pelvic sidewalls indicate stage 3 disease and hence inoperable disease.
Blood urea/ Serum creatinine Obstruction of the ureters from tumor spread may lead to renal failure.
Liver function tests To investigate for liver metastases.
CT scan To determine the extent of disease spread within the pelvis.[2]
MRI MRI of the abdomen and pelvis provides accurate information of the local spread of disease. MRI also allows assessment of the involvement of pelvic lymph nodes.[2] Assessment of the integrity of the ureters was previously carried out by intravenous urogram, this practice has being superseded by the use of MRI.
Chest X-ray To exclude lung metastases.
Cystoscopy To investigate for bladder wall involvement.
References
  1. PECORELLI S, ODICINO F. Cervical cancer staging. Cancer J [online] 2003 Sep-Oct, 9(5):390-4 [viewed 31 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/14690314
  2. BIPAT S, GLAS AS, VAN DER VELDEN J, ZWINDERMAN AH, BOSSUYT PM, STOKER J. Computed tomography and magnetic resonance imaging in staging of uterine cervical carcinoma: a systematic review. Gynecol Oncol [online] 2003 Oct, 91(1):59-66 [viewed 31 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/14529663

Management - General Measures

Fact Explanation
Patient education Provide information regarding the natural progression of the disease, aetiology, investigations and treatment options available. Counsel the patient regarding the prognosis of the condition. Adequate information should be provided on the stage of the disease and proposed management plan. Patient wishes should be considered when finalizing the management plan.
Psychological support Diagnosis of malignancy may cause distress in the patient and family.[1] Provide counseling and psychological support.
Optimize patient fitness if surgery is considered Patients undergoing curative surgery require pre-operative optimization. A pre-existing diabetes mellitus, hypertension and hyperlipidaemia require optimization of pharmacological therapy. Monitor and control blood glucose and blood pressure prior to surgery. Correct anemia if present.
Prevention of cervical carcinoma Screening with pap smear cytology has significantly improved the outlook of prognosis of cervical carcinoma patients. It helps in early detection and specific therapy can be initiated promptly. Health education programmes on sexual health have also shown to be a successful preventive intervention.[2]
References
  1. KOBAYASHI M, OHNO T, NOGUCHI W, MATSUDA A, MATSUSHIMA E, KATO S, TSUJII H. Psychological distress and quality of life in cervical cancer survivors after radiotherapy: do treatment modalities, disease stage, and self-esteem influence outcomes? Int J Gynecol Cancer [online] 2009 Oct, 19(7):1264-8 [viewed 01 August 2014] Available from: doi:10.1111/IGC.0b013e3181a3e124
  2. SHEPHERD J.. Cervical cancer and sexual lifestyle: a systematic review of health education interventions targeted at women. [online] 2000 December, 15(6):681-694 [viewed 01 August 2014] Available from: doi:10.1093/her/15.6.681

Management - Specific Treatments

Fact Explanation
Treatment options The most appropriate treatment option should be selected according to the stage of the disease and patient age, fertility wishes & fitness. Curative treatment options include surgery and chemo-radiation.[1]
Wide local excision Loop biopsy or knife cone biopsy is adequate for preclinical stage 1a disease. It is important ensure that the excision margins are clear of tumor cells and that all pre-invasive disease is removed. Failure to do so requires a repeat biopsy of the cervix. Wide local excision is adequate for these small volume tumors and carries the advantage of preserving the chances of fertility.
Radical hysterectomy with pelvic node dissection (Wertheim’s hysterectomy) Tumors staged as 1b require radical curative surgery. This procedure involves removal of the whole cervix, uterus, parametrial tissue and the upper third of the vagina. The obturator, external iliac and internal iliac lymph nodes are removed. Wertheim’s hysterectomy is usually performed in pre-menopausal patients. Common complications of the disease are bladder atony, sexual dysfunction and lymphoedema. The ovaries can be preserved in pre-menopausal women and prevent iatrogenic menopause. Despite the radical nature and high complication rate, surgery carries a high cure rate.[2]
Radical trachelectomy Radical trachelectomy is a minimally invasive surgery that could be carried out in patients who have marginal stage 1a2 disease which is staged as 1b1. In this procedure 80% of the cervix and parametrial tissue are excised with resection of the pelvic lymph nodes. This procedure can be carried out by both vaginal and abdominal procedures.[3]The advantage of this procedure is the ability to preserve fertility in young patients. Disadvantages of radical trachelectomy include the difficulty in follow-up and the high risk of cervical incompetence.The success rate of this procedure is limited due to cranial extension and lymph node involvement of the malignancy.
Radiotherapy Patients with stage 1b disease who are unfit for surgery or who are postmenopausal could also be considered for treatment with radiotherapy. Both radiotherapy and surgery in these patients carry similar success rates. Radiotherapy is the treatment of choice for stage 2 disease and above. Radiotherapy can be delivered by external beam radiotherapy (teletherapy) or by internal radiotherapy (brachytherapy). The total dosage required is calculated according to extent of disease and patient tolerance. This is administered as daily fractions over a period of about 4 weeks. Short term complications of radiotherapy : skin erythema and damage, bowel and bladder urgency. Ovaries are highly sensitive to radiation and have a significant risk of iatrogenic menopause. Fibrosis of the initially inflamed structures may give rise to vaginal stenosis, chronic cystitis and radiational enteritis in the long term.
Chemotherapy Chemoradio-therapy has being shown to be associated with a higher success rate compared to treatment with radiotherapy alone.[4] Patients treated with radiotherapy are usually combined with treatment with cisplatin. Chemotherapy is effective to treat distant metastases.
Palliative therapy Patients with incurable disease should be afforded symptomatic therapy. Provide a comforting environment. Pain should be managed with appropriate analgesics. Radiotherapy may be offered to treat symptomatic distant metastases – bone deposits.[5] Provide psychological support.
Managing recurrent disease Treatment is often difficult and is usually treated with radiotherapy.
Management of CIN Low grade CIN (CIN 1) is managed conservatively. The patient is monitored by cytology & coloscopy which are is repeated 6 monthly. Some patients with CIN 1 and CIN 2 may show regression of disease over time.[6] High grade CIN requires treatment with either excision or ablation. The most preferred method of treatment is by LLETZ. Other treatment options include cone biopsy, cold coagulation and cryotherapy.
References
  1. WAGGONER SE. Cervical cancer. Lancet [online] 2003 Jun 28, 361(9376):2217-25 [viewed 01 August 2014] Available from: doi:10.1016/S0140-6736(03)13778-6
  2. JENSEN PT, GROENVOLD M, KLEE MC, THRANOV I, PETERSEN MA, MACHIN D. Early-stage cervical carcinoma, radical hysterectomy, and sexual function. A longitudinal study. Cancer [online] 2004 Jan 1, 100(1):97-106 [viewed 01 August 2014] Available from: doi:10.1002/cncr.11877
  3. CIBULA D, SLáMA J, SVáROVSKý J, FISCHEROVA D, FREITAG P, ZIKáN M, PINKAVOVá I, PAVLISTA D, DUNDR P, HILL M. Abdominal radical trachelectomy in fertility-sparing treatment of early-stage cervical cancer. Int J Gynecol Cancer [online] 2009 Nov, 19(8):1407-11 [viewed 01 August 2014] Available from: doi:10.1111/IGC.0b013e3181b9549a
  4. ROSE PG, BUNDY BN, WATKINS EB, THIGPEN JT, DEPPE G, MAIMAN MA, CLARKE-PEARSON DL, INSALACO S. Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med [online] 1999 Apr 15, 340(15):1144-53 [viewed 01 August 2014] Available from: doi:10.1056/NEJM199904153401502
  5. VAN LONKHUIJZEN L, THOMAS G. Palliative radiotherapy for cervical carcinoma, a systematic review. Radiother Oncol [online] 2011 Mar, 98(3):287-91 [viewed 01 August 2014] Available from: doi:10.1016/j.radonc.2011.01.009
  6. CASTLE PE, SCHIFFMAN M, WHEELER CM, SOLOMON D. Evidence for frequent regression of cervical intraepithelial neoplasia-grade 2. Obstet Gynecol [online] 2009 Jan, 113(1):18-25 [viewed 01 August 2014] Available from: doi:10.1097/AOG.0b013e31818f5008