1. CERVICAL NEOPLASMS Dr. Mashael Alshebaili Assistant Professor of Obstetrics and Gynecology

2. CERVICAL INTRAEPITHELlAL NEOPLASIA (CIN) Normal cervical topography:-  In most normal girls, columnar epithelium is limited to the endocervical canal and the central ectocervix.  The outer ectocervix and the vaginal fornices as well as the rest of the vagina are covered by squamous epithelium.

3. Glandular columnar epithelium (endocervix= cervical canal)

4. Stratified Squamous Epithelium (outer ectocervix )

5.  The two types of epithelia meet at the original squamocolumnar junction SCJ.  During adolescence and first pregnancy (periods of endocrine changes) a new SC junction is formed through the active process of (squmous metaplasia)  The new SCJ is more proximal to the external os than the original.

6.  The area between the two SCJs is THE TRANSFORMATION ZONE T ZONE what type of epithelium is found in the T zone???

8.  Aproximately 95% of squamous intra epithelial neoplasia occurs within the T zone  The commonest etiological factor of cellular abnormality leading to CIN and cancer is high risk HPV infection

9. Other risk factors: Smoking intercourse at young age<20yrs Multiple sexual partners early age of pregnancy high parity Immunocompression (eg.HIV, DM) Low socioeconomic status OCP for > 10 years  adenocarcinoma

10. The sequence goes HPV  preinvasive CIN  invasive Cancer 1 2 3 From 2  3 Key difference is intact basement membrane 8-10 years

11.  HPV cause virtually all cervical cancers  HPV has many serotypes 16,18,31,33,35 high grade CIN, CA 6,11 condylomas, low grade CIN

12.  classification of cytologic abnormalities (reporting): 1.Class system :Inflammation, dysplasia (mild,moderate,severe), CIS, changes suggestive of cancer. 2.CIN system: Inflammation,  CIN1 (mild dysplasia =inner1/3)  CIN2 (moderate dysplasia=inner2/3)  CIN3 (severe dysplasia>2/3,CIS=full thickness) changes suggestive of cancer.

13. 3 ) Bethesda system:  Organisms(Trichomonas)  Reactive cellular changes (inf, IUCD,..)  Atrophy  ASC-US,  Low-grade SIL (LSIL) = HPV+CIN1  High-grade SIL (HSIL) = CIN2+CIN3  Squamous cell carcinoma (SCC)

14.  AGC: atypical glandular cells (endocervical,endometrial,…..,not otherwise specified)  AGC favor neoplastic  Endocervical adenocarcinoma in situ (AIS)  Adenocarcinoma

17. COURSE OF CIN  CIN may regress, persist and remain unchanged, or progress to invasive carcinoma. The latter takes about 10 years (1-15 years).  The percentage of cases becoming invasive is about 15% for CIN I, 25% for CIN II, and 50% for CIN Ill

18. DIAGNOSS Symptoms  CIN has no symptoms.  contact bleeding. Signs  The cervix looks normal.  may show an associated nonspecific lesion as erosion, cervicitis, or leucoplakia.

19.  The diagnosis is made by the routine cervical smear.  If the smear shows abnormal cells the diagnosis must be confirmed by cervical biopsy. This is done using the colposcope to select the site for biopsy.  If the colposcope is not available we do Schiller iodine test to select the site for biopsy.  If the smear is positive and no lesion could be seen by these methods a cone biopsy is done.

20. Normal Pap Smear

21. Pap smear cytological screening methods: 1.Conventional (brush-spatula-slide) 2.Thin-layer,liquid-based cytology More sensitive ( less FN ) DNA typing of HPV can b done 3.Computer-assisted automated cytology 4.Hybrid Capture 2 HPV DNA testing

22. Timing and frequency of pap smear screening:  Within 3 years of onset of intercourse/no later than age 21 Annually  If 3 paps in a row were negative --  less frequent ( every 2-5 yrs) according to the physician

23. TREATMENT I. Destruction of the lesion and whole transformation zone. This. is achieved by cryocautery, electrocautery, diathermy cautery, cold coagulation or laser. The cure rate is about 95%. II. Excision of the lesion and whole transformation zone. This is carried out by laser or by a diathermy loop (large loop excision of the transformation zone: LLETZ also called loop electrosurgical excision procedure: LEEP). Ill. Conization. The cure rate is 99%. It is superior to local destruction and preserves fertility.

24. IV. Hysterectomy. It is rarely done. The indications are: (1) women above 40 years. (2) patients requesting sterilization. (3) the presence of associated pathology needing hysterectomy as fibroids. (4) when it is difficult to follow up the patient by cytology or colposcopy; (5) residual lesion after treatment. However, residual disease can be treated by repeating local destruction, local excision, conization or hysterectomy.  if the lesion involves the upper vagina. Treatment is hysterectomy with removal of upper part of vagina. Alternative to this is conization and laser destruction of the vaginal lesion.

25.  Some gynaecologists treat CINI conservatively. In this case cervical smear is repeated every 6 months, and any associated infection is treated.  CINI becomes invasive in about 15%, regresses in about 30%, and remains unchanged in the rest.  FOLLOW-UP Follow-up by cytology every 3 months for one year and then every 6 months for 5 years and then yearly indefinitely.

26. INVASIVE CERVICAL CARCINOMA  Incidence. It varies between 15 to 35 per 100,000 females per year. It varies considerably from country to country and from race to race.  Age. The commonest age incidence is 45- 55 years. The tumour, however, can occur at any age and it is reported that there is another peak at the age of 35.  Aetiology. The cause of cervical cancer is unknown, but the predisposing factors similar CIN.

27.  SITES 1. Carcinoma of the portio vaginalis or ectocervical carcinoma (90%). It arises fromthe squamous epithelium covering the vaginal portion of the cervix and always starts at or near the squamocolumnar junction at the external os (transformation zone). 2. Endocervical carcinoma (10%). It arises from the columnar epithelium lining the cervical canal or cervical glands.

28. MODE OF SPREAD 1. Direct spread. 2. Lymphatic spread. 3. Bloodstream. 4. Surface implantation (seeding).

29. CAUSES OF DEATH FROM CERVICAL CANCER (1) Uraemia, the commonest cause of death (50%), due to bilateral ureteric obstruction and urinary tract infection. (2) malignant cachexia. (3) infection as parametritis, peritonitis or septicaemia. (4) severe haemorrhage from eroding a big vessel. (5) pulmonary embolism due to infection and thrombophlebitis. (6) metastases in vital organs as liver or brain. (7) complication of treatment, the primary mortality from Wertheim operation is about 1% and from radiotherapy is less than 1%.

30. DIAGNOSIS  Symptoms 1. Asymptomatic. 2. Vaginal bleeding.. It starts as contact bleeding occurring after coitus, douching or vaginal examination. Later on the bleeding is irregular and variable in amount. 3.Vaginal discharge. It is the second commonest symptom. At first, it is slight and watery, later on it becomes blood stained and offensive due to ulceration and infection.. 4. Vaginal mass and dyspareunia. 5. Pain. It is a late sympto

31.  Signs 1. General examination. This may show cachexia, evidence of uraemia,supraclavicular or inguinal lymph nodes metastases, and oedema of lower limbs which indicates lymphatic obstruction in the pelvis. 2. Abdominal examination. The abdomen should be carefully examined forenlarged liver, kidneys, abdominal masses, and ascites

32. 3. The pelvic examination In early cervical cancer may reveal a cervix that appears normal, especially if the lesion is endocervical.  Visible disease may take several forms: ulcerative, exophytic, granular, or necrotic..

33. c. Investigations 1. Cervical biopsy.. 2. Cystoscopy to diagnose infiltration of the bladder. Done as a routine in every case. 3. Sigmoidoscopy or barium enema if there are bowel symptoms as pain or bleeding. 4. Chest X-ray is done as a routine. 5. Intravenous pyelogram to show the condition of the ureters and kidney function.

34. 6. Computerized tomography (CT) scan to the pelvis and abdomen. It shows the size of the tumour, infiltration of the parametrium, metastases in the pelvic and aortic lymph nodes and liver, and diagnoses hydronephrosis. 7. Magnetic resonance imaging (MRI) is more accurate than CT scan but it is costly.

35. 8. Bone scan. Not done as a routine but only when symptoms or signs suggest metastases 9. Estimation of serum tumour markers; cancer antigen-12S (CA-12S), (SCCA), (CEA), and (TA-4) to follow response to treatment and to detect recurrence. 10. Examination under general anaesthesia must be done to determine the extent of the growth. It is essential for clinical staging.

36. CLINICAL STAGING (FIGO CLASSIFICATION, 1994) Stage 0: Intraepithelial carcinoma (carcinoma in situ). Stage I: Invasive carcinoma limited to the cervix or extending to the body of the uterus. lA: Microinvasive carcinoma (diagnosed only by microscopy). IB All other cases of stage 1 IB1: Lesion 4 cm or less in size. IB2: Lesion greater than 4 cm in size.

37. Stage II: IIA: Involvement of the upper two-thirds of the vagina. lIB:Infiltration of the parametrium on one or both sides but not reaching the pelvic wall Stage Ill: IlIA: Involvement of the lower third of the vagina. IIIB: Infiltration of the parametrium up to the pelvic wall or cases with hydronephrosis or nonfunctioning kidney. Stage IV: IVA: Spread to the bladder or rectal mucosa. IVB: Spread outside the true pelvis.

38. SUMMARY OF TREATMENT 1. Stage lAl: Simple hysterectomy or conization. 2. Stage IA2: Extended hysterectomy. 3. Stage IB and IIA: Wertheim operation or radiotherapy. The treatment is individualized e.g. if the patient is young surgery is preferred to preserve ovarian function and allow normal intercourse, as radiotherapy destroys ovarian function and causes vaginal stenosis and dyspareunia.

39. 4. Stage lIB: Radiotherapy. 5. Stage Ill: Radiotherapy. 6. Stage IV: Palliative treatment including palliative radiotherapy, pelvic exenteration, chemotherapy and drugs to relieve pain.