PREMALIGNANT AND MALIGNANT DISEASE OF CERVIX (1).pptx

Cervical cancer is the growth of abnormal cells in the lining of the cervix. The most common cervical cancer is squamous cell carcinoma, accounting for 70% of cases. Adenocarcinoma is less common (about 25% of cases) and more difficult to diagnose because it starts higher in the cervix.

1. PREMALIGNANT AND MALIGNANT DISEASE OF CERVIX ASIYA NAZ (202023) SANA NIAZ (202059) MUSA KHAN (202075) ABDUL QADEER KHAN (202019)

2. LEARNING OBJECTIVES Premalignant (CIN) Epidemiology Pathophysiology GRADES DIAGNOSIS AND INVESTIGATIONS TREATMENT MALIGNANT (CERVICAL CARCINOMA) INTRODUCTION CLINICAL FEATURES STAGING DIAGNOSIS AND INVESTIGATION TREATMENT

3. PREMALIGNANT DISEASE OF CERVIX

4. EPIDEMIOLOGY AND AETIOLOGY HPV infection (100 different types) HPV 6 and 11 cause benign warts H igh-risk types HPV 16, 18, 31, 33 and 45 cause cervical cancer HPV infection is spread during sexual intercourse (80%) Smoking increases the risk of persistent infection. Women who are immunocompromised (HIV) L ong-term immunosuppressive therapy

5. PATHOPHYSIOLOGY 5 viral E7 protein binds the hypo phosphorylated (active) form of RB and promotes its degradation via the proteasome pathway Integration of HPV DNA into basal epithelial cells transformation zone (TZ) is defined as the area between the original SCJ and the current SCJ where the epithelium changes from columnar to squamous epithelium over time.

6. 6 viral E6 proteins of high-risk HPV subtypes, which bind to the tumor suppressor protein p53 and promote its degradation by the proteosome This disordered immaturity within the epithelium is called ‘ cervical intraepithelial neoplasia’ (CIN)

7. GRADES OF CIN:-

8. DIAGNOSIS AND INVESTIGATIONS:- History Examination ( GPE, per speculum, bimanual) Pap smear Cervical cytology HPV testing with cervical screening Colposcopy 8

9. CERVICAL CYTOLOGY liquid-based cytology (LBC) , a small brush is used to sample cells from the TZ, and the brush head is placed in a fixative. This is then exa mined under the microscope. GRADES:- low grade (minor cytological abnormalities showing mild dyskaryosis or borderline change) high-grade(moderate and severe dyskaryosis) SENSITIVITY:- A single cervical smear for high-grade CIN detection is between 40% and 70% Women who attend regularly for cervical cytology have a very low risk of developing cervical cancer. WHO suggests a regular screening interval of every 3 years when using VIA or cytology as the primary screening test, among both the general population of women and women living with HIV. 9 Normal LBC Severe dyskaryosis

10. National Cervical Screening Program 10 Under 25 Only if sexually active 25 to 49 Every 3 years 50 to 64 Every 5 years 65 or older Only if a recent test was abnormal

11. HPV testing in cervical screening If a woman tests high-risk HPV negative , her risk of developing cervical cancer over the next 5–10 years is exceptionally low. HPV-negative women ( 95%) are returned to routine recall. High-risk HPV-positive women are referred for colposcopy Primary HPV screening is now performed first in most countries( including the UK) even before cervical cytology as it is automated and achieves a high throughput. WHO recommends using HPV DNA detection as the primary screening test rather than VIA or cytology in screening and treatment approaches among both the general population of women and women living with HIV.

12. COLPOSCOPY Colposcopy is the examination of the magnified cervix using a light source (magnification 5-20 fold) Diagnostic and therapeutic purpose Acetic acid (areas of increased cell turnover, including CIN, appear white) Iodine solutions (CIN areas fail to stain brown when iodine is applied) Angiogenesis could be observed Low grade ( subsequent colposcopy and cytology 6 months later) High grade (can be treated in the clinic on the same visit) A biopsy could be performed for a definitive diagnosis Each colposcopy service undergoes a rigorous external quality assurance assessment every 5 years to ensure high standards 12

13. TREATMENT:- High-grade CIN requires treatment, usually with excision or ablation. Low-grade CIN regresses spontaneously in up to 60% of cases; therefore, close follow-up with colposcopy and cytology 6 months after initial diagnosis is favored as this avoids overtreating lesions that might have regressed. 3. LOOP DIATHERMY 13

14. COLD COAGULATION ( CRYOTHERAPY) The treatment involves placing a hot. probe on the cervix in outpatients under local anesthetic. For both high and low-grade specimens. Does not provide a specimen. 5. CONE BIOPSY:- Provides specimen. Requires general anesthesia. The patient may develop cervical stenosis and incompetence (5%). AFTER TREATMENT :- ‘Test of cure’ after 6 months (high-risk HPV test and cytological assessment). If negative cervical screening in 3 years. If positive, repeat colposcopy is indicated to identify any residual, untreated CIN. 14

15. HPV VACCCINATION:- In the UK it is aimed at 12–13-year-old girls The bivalent vaccine ( cervarix ) prevents persistent infection with HPV types 16 and 18, which together are responsible for more than 70% of cases of cervical cancer. Quadrivalent vaccine (Gardasil) (HPV 16,18, 6 and 11) Gardasil 9 ( HPV 6,11,16,18, 31,33,45,52 AND 58) Current vaccination strategies are unlikely to result in the eradication of cervical cancer because other high-risk HPV types are not included and uptake is not universal 15

16. MALIGNANT DISEASE OF THE CERVIX 16 Cervical cancer

17. The average age of patients with invasive cervical carcinoma is 45 years. Squamous cell carcinoma (70%) Precursor: CIN Adenocarcinomas Precursor: CGIN (lesions reside in the endocervical canal) But this percentage is reversed in higher developing countries such as UK. These are usually picked up as incidental finding after loop excision for pre-cancerous disease. 17

18. CLINICAL FEATURES: Asymptomatic Abnormal bleeding (postcoital (PCB), prolonged, intermenstrual (IMB) or postmenopausal (PMB) bleeding) Vaginal discharge (blood-stained, foul-smelling) Dyspareunia Pelvic pain Weight loss. 18

19. CLINICAL FEATURES: 19 In stages III–IV, patients may experience a number of distressing symptoms including: Pain (malignant infiltration of the spinal cord) Incontinence (due to vesicovaginal fistulae) Anemia (from chronic vaginal bleeding) Renal failure (from ureteric blockage) On pelvic and speculum examination, a cervical mass that bleeds on contact and if advanced disease, a hardness and fixity of the tissues. Very occasionally, the diagnosis can be missed as some tumours are endophytic rather than exophytic and therefore less clinically revealing.

20. STAGING AND PROGNOSIS (lung, liver, bone and bowel).

21. DIAGNOSIS: HISTORY EXAMINATION (GPE, per speculum, bimanual, abdominal, pelvic) INVESTIGATIONS: Biopsy MRI abdomen and pelvis Chest X-ray Examination under anesthetic Rectovaginal examination under anesthetic Cystoscopy 21

22. TREATMENT It depends on: Stage of the disease The requirement for future fertility The patient’s performance status 22

23. Stage IA Small lesions must be removed with a clear margin of excision , and the preinvasive disease (CIN) that invariably coexists should also be completely excised as the cancer is often multifocal. If the preinvasive disease is not completely excised then a repeat loop biopsy or knife cone biopsy must be carried out. For microscopic lesions (stage IA1), local excision with good clear margins is all that is required. This allows fertility to be preserved and a hysterectomy is not necessary. 23

24. Stages IB–IV In stage IB1, radical hysterectomy and bilateral pelvic node dissection ( Wertheim’s hysterectomy ) is standard of care. Complications: Bladder dysfunction (atony) Management: intermittent self-catheterization Sexual dysfunction (due to vaginal shortening) Lymphoedema (due to removal of the pelvic lymph nodes) These patients present with a wooden, heavy feeling to the legs with swelling and reduced mobility. Management includes leg elevation, good skin care (e.g. avoid shaving), massage and occasionally compression stockings. For young women who have not completed their families , radical trachelectomy (surgical removal of the cervix and upper part of the vagina) and bilateral pelvic node dissection is an alternative. 24

25. In early-stage IB disease: Pelvic radiotherapy has similar success rates to surgery and therefore this treatment is considered in women who are too overweight for radical surgery or who are anesthetically unfit. Stages II–IV disease: radiotherapy (with or without chemotherapy) becomes the optimal treatment. Surgery in isolation is problematic as complications can occur (severe haemorrhage ). Incomplete excision of cancer by surgery requires adjuvant postoperative radiotherapy and the combined treatments can lead to high complication rates. 25

26. RADIOTHERAPY : Treatment is delivered in two ways: External beam radiotherapy (teletherapy) In external beam radiotherapy, the source of the radiation is from a machine called a linear accelerator, and radiation is delivered to the pelvis a distance from the patient. The dose of radiotherapy is 45 Gy in total, given in several treatments or ‘ fractions ’ as an outpatient over 4 weeks . Although this treatment is given daily, the time of each fraction is no more than 10 minutes. Internal radiotherapy (brachytherapy) The source of the radiation is usually selenium and patients generally have to undergo an examination under anaesthetic to insert the rods into the uterus. These rods are then attached to the radiotherapy source. Its harmful effects on the bladder and bowel are minimized as its effects are targeted only 5 mm from the rod. 26

27. SIDE EFFECTS OF RADIOTHERAPY: Lethargy Bowel and bladder urgency Skin erythema-like sunburn Symptomatic treatment is usually required, such as antiinflammatory creams for skin. Bowel damage leads to malabsorption and mucous diarrhea. 5% of patients experience bowel perforation. Vaginal stenosis can cause sexual pain, bladder damage can lead to cystitis-like symptoms, haematuria . Radiotherapy-induced menopause in premenopausal women. 27

28. Chemotherapy (cisplatin) is ideally given in conjunction with the radiotherapy. Palliative treatment. 28

29. Thank you reFerences: Gynecology by Ten Teachers WHO guideline for screening and treatment of cervical pre-cancer lesions for cervical cancer prevention Singh RH, Erbelding EJ, Zenilman JM, Ghanem KG. The role of speculum and bimanual examinations when evaluating attendees at a sexually transmitted diseases clinic. Sex Transm Infect. 2007 Jun;83(3):206-10. doi : 10.1136/sti.2006.023309. Epub 2006 Nov 15. PMID: 17108005; PMCID: PMC2659094.