Cervical Cancer By Salah Taha Fayed Prof. Gynecologic Oncology Ain-shams Univ. Cairo-Egypt

Cervical Cancer: Outline It is malignant tumor of the cervix uteri With ovarian and endometrial cancer they comprise the major gynecological cancers Commonly it is carcinoma (epithelial) but rarely sarcoma and lymphoma arise in the cervix.

Epidemiology In USA it is the third genital cancer after endometrial and ovarian cancer The incidence is about 10/100000/year In Latin America it is the first genital cancer It is more prevalent among black race It is more common in low social class Its peak incidence is between 45-50 years

Epidemiology cont. The following Increase the risk of cervical cancer: Smoking Early sexual activity Multiple sexual partners Exposure to a male with multiple partners Sexually transmitted diseases namely HPV and HIV infection

Epidemiology cont. Almost all cases of invasive cervical cancer are positive for Human papilloma virus Concomitant HIV infection increases the aggressiveness and worsen the prognosis No evidence that HSV type II infection increases the risk of cervical cancer

Pathological Types 85-90 % are squamous cell carcinoma SCC arising from the transformation zone 10-15 % are adenocarcinoma arising from the endocervical columnar epithelium or glands The formerly mentioned risk factors and epidemiological criteria apply only to the SCC type

Pathogenesis and Natural History The exact cause is not yet identified As in most other cancers, the genetically predisposed patient when exposed to risk factors as HPV infection this starts the malignant transformation Over-expression of Oncogenes or suppression of Tumor Suppressor Gene could be the mechanism of malignant transformation

Pathogenesis cont. Invasive SCC is a disease that have pre-malignant lesions (CIN) CIN with its 3 grades is amenable to conservative, relatively simple and curative treatment Early detection in the pre-malignant stage is the corner stone of decreasing the incidence of invasive SCC in developed countries

Cervical Cancer: Stages Generally speaking 4 stages as other cancers Stage I Cervix Only Stage II A Vagina short of lower third II B Parametrium NOT pelvic wall Stage III A Vagina lower third III B Parametrium to pelvic wall Stage IV A Bladder or Rectal Mucosa IV B Distant metastases

Stage I

Stage II

Stage I and II

Stage III

Stage IV

Stage III and IV

Spread of Cervical Cancer Local to the vagina, parametrium, uterine body(uncommon), bladder and rectum Lymphatic to: (A) parametrial lymphatics, (B) pelvic LN (externa, internal ileac and obturator) (C) Common iliac LN and Periaortic LN Blood: Distant metastases are rare and late

Gross Appearance Exophytic friable polypoid mass arising from the ectocervix that bleeds easily Endophytic infiltrating appearing as a stony hard cervix with little ulceration Ulcerative type An ulcer that erodes the cervix and adjacent vagina Barrel shaped lesion is a variety of exophytic lesions arising within the endocervical canal

Clinical Presentation I. Early: Serosanguinous vaginal discharge Contact bleeding II. Late: Offensive vaginal discharge Irregular spontaneous bleeding III. Very late: Persistent severe back pain radiating to the lower limb, lower limb edema, Uraemic syndrome, Urine and or stool incontinence

Investigations To prove diagnosis: Biopsy & Histopathology Staging: Examination under anesthesia, Cystoscopy, IVU, and Abdomenopelvic CT with contrast To prepare for surgery: CBC, blood sugar, Liver functions, kidney functions, Urine analysis, ECG and Chest X-Ray

Rectovaginal Examination

Treatment Modalities Two main modalities are used: Surgery: Radical hysterectomy Radiotherapy: with or without chemotherapy Surgery may be followed by Radiotherapy

Cervical Cancer: Treatment Early stages: IB and IIA could be managed by either Wertheim’s Radical hysterectomy or Radiotherapy with equal results Late stages: IIB, III, and IV are treated by radiotherapy with or without chemotherapy Rarely pelvic exentration is suitable for central disease extending to bladder or rectum without parametrial infiltration or for central recurrence after Radiotherapy

Wertheim’s Radical Hysterectomy Indicated in surgically fit relatively young patients with stage IB or IIA disease Uterus, parametrium, upper third of the vagina and pelvic lymph nodes are removed in this operation A major surgery that requires good experience in oncological surgery Bladder dysfunction, ureteric injury, and vascular injury are its main complications

Radiotherapy An alternative to surgery for stages IB and IIA Is the primary treatment of choice for all higher stages Can be adjuvant to surgery if positive nodes were found or infiltrated resection margins

Radiotherapy cont. Brachytherapy: Intracavitary applicator that deliver cytotoxic dose to the cervical tumor, parametrium and to the lateral pelvic wall where the pelvic lymph nodes are situated Teletherapy: External beam of megavoltage X-Ray delivered to the pelvis and sometimes to the para-aortic LN

Brachytherapy & Teletherapy

Radiotherapy cont. It can not preserve the ovaries in contrast to the surgery Radiation cystitis and proctitis, rectal fibrosis, flare up of infections and urinary fistula are among its complications Intestinal fistulas are serious complications of extended field irradiation

Role of Chemotherapy To shrink the tumor size in bulky stage IB2 To enhance the cytotoxic effect of radiotherapy as radiosensitizer Cis-platinum alone or in combination with 5-fluorouracil (5-fu) are the most commonly used cytotoxic drugs

Cervical Cancer prognosis Prognostic factors include: Stage (most important) Tumor size Lymph node status Lymph-vascular space invasion Grade of differentiation Concomitant HIV infection

Prognosis cont. Five year survival for different stages are: Stage I ………….. 90% Stage II …………. 75% Stage III ………… 40% Stage IV ………… 15% NB: the above are approximated round figures agreeing with most of the studies using different treatment modalities

Less Important Issues The following are less important issues to know for the under-graduate student

Microinvasive Cancer Stage IA Microscopically diagnosed not clinically apparent disease Width of the lesion <7mm Depth of invasion < 5mm Stage IA1 depth of invasion <3mm Stage IA2 depth of invasion 3-5 mm

Stage IA microinvasive cont. LN metastases occur in 1% stage IA1 Treatment is extrafascial hysterectomy without resection of LN, vaginal cuff or parametrium LN metastases occur in 6% stage IA2 Treatment is the same like truly invasive disease

Microinvasive Stage IA

Cervical Cancer During Pregnancy The most common genital tract cancer during pregnancy Usually present by vaginal bleeding which is misdiagnosed early as threatened abortion and later as antepartum hemorrhage

Cervical Cancer during pregnancy cont. Treatment depends on: stage, gestational age, desire for the baby, religious background of the patient Modality of treatment dictated by the stage

Cervical Cancer during pregnancy cont. Before 24 weeks pregnancy is usually sacrificed and surgical or radiation treatment start immediately After 24 weeks viability may be waited

Conclusion The best treatment results can be achieved in the pre-invasive stages Earlier stages carry better prognosis Modalities of treatment are surgery, Radiotherapy with or without chemotherapy Sound sexual behavior is crucial to minimize the risk of STDs and cervical Cancer Cervical Cancer could be potentially preventable disease through early detection programmes

Thank You Dr. Salah Fayed