Screening for Cancer Cervix PDF

Screening for Cancer Cervix Department of Obstetrics and Gynaecology Objectives: By the end of this lecture, the student should be able to: Identify the high-risk women for Cancer Cervix. Describe the pathology and grades of CIN. State the clinical presentation of CIN. Outline the screenin...

Screening for Cancer Cervix Department of Obstetrics and Gynaecology Objectives: By the end of this lecture, the student should be able to: Identify the high-risk women for Cancer Cervix. Describe the pathology and grades of CIN. State the clinical presentation of CIN. Outline the screening program for early detection of pre- cancerous lesions. List and interpret different screening tools. Outline the management plan for women with CIN. Cervical Erosion (Ectopy) It is a Bright Red area around the external os due to replacement of the stratified squamous epithelium of the Ecto-cervix with the Endo- cervical columnar epithelium, which is thin and shows the underneath blood vessels. Cervical Erosion (Ectopy) In Young Girls: due to the growth of uterus → eversion of the cervix out with its lining columnar epithelium below the level of the external cervical os → Cervical Ectopy → the squamo-columnar junction comes to lie outside the external cervical os (Original SCJ).  Cervical Erosion (Ectopy) In Adult Women: columnar mucus-secreting epithelium of the endocervix meets the squamous epithelial covering of the ectocervix at the level of external os → the entire “exposed” cervix is covered by squamous epithelium (squamous metaplasia) → endocervical columnar epithelium is not visible to the naked eye (New SCJ). Squamo-Columnar Junction  Cervical Erosion (Ectopy) Remodeling occurs continuously with regeneration of both squamous and columnar epithelium. The geographical area (Dynamic zone) between the original SCJ and the new SCJ is called: Transformation Zone New SCJ Squamous metaplasia is a progressive, permanent transformation of columnar into squamous epithelium Border between newly formed squamous epithelium and columnar epithelium called the new SCJ. Majority of cervical cancers and precursor lesions arise from immature squamous metaplasia (leading edge of new SCJ). Adequate colposcopy requires visualization of the entire New squamocolumnar junction (SCJ). Cervical Erosion (Ectopy) Aetiology Congenital erosion (Maternal Oestrogen effect). Hormonal erosion: after Puberty, Pregnancy, and women on CHCs. Inflammatory erosion: Acute or Chronic cervicitis. Cervical Erosion (Ectopy) Clinical picture: Symptoms: Excess mucous discharge. Contact bleeding (Post-coital Bleeding). Symptoms of cervicitis (if present). Cervical Erosion (Ectopy) Clinical picture: Signs: Speculum examination: – Flat erosion: → red flat area. – Papillary erosion: → raised folds. – Follicular erosion: → red glandular distension. Digital examination: Velvety sensation and occasional contact bleeding. Cervical Erosion (Ectopy) Investigations: Wet-mount vaginal smear. HVS for C&S. Cervical Pap smear: to exclude epithelial and glandular dysplasia and malignancy. Cervical Erosion (Ectopy) Treatment: Hormonal erosion: treatment is needed if the case persists > 3 months. Antibiotics to treat associated cervical infection. Cauterization of the ectocervix for resistant cases after confirmed –Ve 3 Pap-smears. Cervical Erosion (Ectopy) Methods of cervical Cauterization: Chemical Cautery. Electrocautery. Cryocautery (Freezing). Laser Cauterization. Cervical Intraepithelial Neoplasia Cervical carcinoma was once the most frequent form of cancer in women around the world. The widespread use of Papanicolaou (cytologic) screening of women + HPV vaccination have dramatically lowered the incidence of invasive tumors → the 2nd common female genital tract malignancy after endometrial carcinoma.  Cervical Intraepithelial Neoplasia By contrast, the incidence of precursor CIN has increased → this being in part attributable to early case finding by the Pap smear, and in part due to increase sexual promiscuity (Casual Sex). Cervical Intraepithelial Neoplasia It is important to emphasize here that All invasive cervical squamous cell carcinomas arise from precancerous epithelial changes referred to as CIN. However, Not all cases of CIN will progress into invasive cancer, and indeed many persist without change or even regress. Cervical Intraepithelial Neoplasia Screening Tests: Pap-Smear: Sensitivity 55% & Specificity 85%. HPV-DNA testing in Cervico-vaginal secretions. Co-testing or Reflex HPV testing. +Ve → Biopsy Visual Inspection (VIA and VILI): Low resource settings. Colposcopy ± Cone biopsy. Pap-Smear Papanicolaou Test: A cytological screening test for cervical cancer in which a cell sample taken from the cervix is examined for cellular abnormalities. Pap-Smear Types: Conventional pap smear: The sample is spread on a glass slide. Liquid-based cytology (LBC): The sample is placed into a fixative solution that preserves cells. LBC has some advantages: – Ability to test for HPV-DNA from the same media. – Elimination of mucus, blood and cellular debris. – Standardized technique with saving of cells. Bethesda classification (2001) The Cytologic Pap-Smears interpreted into: NILM: Negative for intraepithelial lesion or malignancy. LSIL: Low-grade Squamous Intraepithelial Lesion. HSIL: High-grade Squamous Intraepithelial Lesion. SCC: Squamous Cell Carcinoma. ASC-US: Atypical Sq. Cells of Undetermined Significance. ASC-H: Atypical Squamous Cells - Cannot exclude HSIL. AGC: Atypical Glandular Cells. HPV-DNA Testing A screening test for cervical cancer in which cells collected from the cervix are tested for infection with high-risk HPV serotypes. HPV viral DNA is detected using PCR: – Amplification of HPV fragments. – Direct genome detection. – Amplification and genotyping of HPV 16 and 18. HPV-DNA Testing Although HPV DNA testing can identify women at- risk for cervical cancer, most sexually active women will contract cervical HPV infections at some point in their lifetime. Types of HPV DNA testing: 1. Primary HPV test (done alone). 2. Co-test with concurrent Pap-smear. 3. Reflex / Triage HPV test (requested upon abnormal Pap-smear). Cervical Biopsy Interpretation On the basis of Histopathology of cervical biopsy, precancerous changes are graded as follows: Mild cervical dysplasia = CIN-I. Moderate cervical dysplasia = CIN-II. Severe dysplasia = CIN-III - Carcinoma in-situ (CIS) Cervical Intraepithelial Neoplasia Epidemiology and Pathogenesis: Incidence in US: 7.4/100,000 The peak age incidence of CIN is about 30 years, whereas that of invasive carcinoma is about 45 years. Prominent risk factors : – Early onset of sexual activity. – Multiple sexual partners. – Women with uncircumcised male partner. – Infection with high-risk HPV (16, 18), HSV, HIV. Cervical Intraepithelial Neoplasia HPV 16: Squamous cell carcinoma HPV 18: Cervical Adenocarcinoma. Cervical Intraepithelial Neoplasia Indeed, HPV can be detected in about 85-90% of CIN and invasive neoplasms, and more specifically, certain high-risk HPV sero-types: (16, 18, 31, 33, 35, 39, 45, 52, 56, 58, and 59). By contrast, Condyloma Accuminata, which are benign lesions, are associated with infection by low-risk sero-types (6, 11, 42, and 44).  HPV Vaccine Indicated for females aged 9-45 years. Cervarix®: Protects against HPV types 16 and 18 Gardasil®: Protects against HPV types 6,11, 16 and 18. Gardasil-9®: HPV types 6,11, 16, 18, 31, 33, 45, 52, 53. The vaccine is most effective if received before the onset of sexual activity and is less likely to be effective after HPV exposure (3 doses). Additional Risk Factors Persistent infection with high-risk HPV 16, 18. Tobacco (Cigarette) smoking. Long-term use of OCPs > 5 Years. High-parity > 5 Children. Low Socio-economic State with Poor Nutrition. Immunodeficiency / Renal Failure / Cytotoxic drugs / HIV. Diethylstilboestrol (DES) exposure. Visual inspection with acetic acid (VIA) VIA Category Clinical Findings Test-negative No acetowhite lesions or faint acetowhite lesions; polyp, cervicitis, Nabothian cysts. Test-positive Sharp, distinct, well-defined, dense (opaque/dull white) aceto-white ± Leukoplakia or Warts. Suspicious Clinically visible cauliflower-like growth or for cancer ulcer oozing or bleeding on touch. Test-Negative Test-Positive Suspicious for Cancer Visual inspection with Lugol’s iodine (VILI) VILI Category Clinical Findings Test-negative Squamous epithelium turns brown while the columnar epithelium does not change colour. Test-positive Well-defined, bright yellow iodine non-uptake areas touching the squamo-columnar junction (SCJ) or close to the os if SCJ is not seen. Suspicious for Clinically visible cauliflower- like growth or ulcer cancer oozing or bleeding on touch. Test-Negative Test-Positive Suspicious for Cancer Colposcopy It is a procedure using a colposcope to examine the cervix, vagina, vulva, and anus for pre- cancerous lesions → Magnified visualization of the epithelium to guide biopsy sampling for histopathological examination. Colposcopy Inspection of cervix with a stereoscopic binocular illuminated microscope with a magnification up to 40x. It is indicated when Pap-smear is abnormal. Technique: – Normal Saline washing. – Acetic acid 5% test (cause coagulation of protein-rich cells as in columnar & metaplastic cells → Aceto-white area). – Schiller’s iodine 5% test (Iodine dye taken by glycogen-rich squamous epithelial cells → Suspicious are remains unstained). – Green filter to visualize abnormal vasculature.  Colposcopy Colposcopic Findings Classification (2002) I. Normal colposcopic findings II. Abnormal colposcopic findings: (Aceto-white epithelium, Iodine negativity, Atypical vessels). III. Colposcopic features suggestive of invasive cancer: (Dense aceto-white area, erosion, ulcer, irregular & coarse punctation and mosaic, atypical corkscrew or comma-like vessels). IV. Unsatisfactory colposcopy (the new SCJ is not visible). V. Miscellaneous findings (Condyloma, ectopy, polyp). Cervical Biopsy A cervical biopsy is usually done (as a part of colposcopy) when abnormalities are found during pelvic examination, Pap-smear, and/or HPV test. Types: Punch biopsy (2-4 targeted biopsies 65 years: No screening is necessary (-Ve screen last 10 years) Women with Total hysterectomy for a benign lesion. Vaccinated women or patients with Subtotal Hysterectomy should continue age specific screening protocol. Cervical Precancerous Lesions Management Plan: Results of Pap-smear: – Normal smear → No further management → To follow her Screening protocol. – Abnormal smear → (HPV-Triage testing): Low-risk patient with LSIL or ASC-US → Medical treatment of Cervicitis + Follow-up after 3 months to repeat the Pap-smear (Treatment of CIN-I). Low-risk women: HPV-DNA test -Ve, and with a Single partner. Cervical Precancerous Lesions Management Plan: – Abnormal smear → (HPV-Triage testing): High-risk patient with LSIL or ASC-US, or Patient with HSIL or ASC-H ± HPV test positive → Colposcopy + Biopsy: CIN-II → Destruction or ablation (Cryotherapy or CO2 laser ablation). CIN-III → Expedited management: – Young women → Conization (LEEP/CKC/CO2 laser). – Elderly women → Total Hysterectomy. High-risk women: HPV-DNA test +Ve, or with Multiple partners Cervical Precancerous Lesions Management Plan: Results of Pap-smear: – Abnormal smear → (HPV-Triage testing): AGC → Colposcopy + Endocervical curettage + Endometrial sampling. Cervical Intraepithelial Neoplasia (CIN) Follow-up: To exclude residual CIN specially in large lesions, CIN-III, older patients, incomplete margins, or difficult treatment. To detect recurrence. To identify problems since treatment. Plan: → Colposcopy/6 months + Cytology/year → For 5 years. Resources: – Berek & Novak’s Gynecology: Jonathan Berek and Deborah Berek - Wolters Kluwer Publications - 16th edition, 2020. PP: 833. – Shaw’s Textbook of Gynaecology: Sunesh Kumar, VG Pandubidri, Shirish Daftary - Elsevier Publication - 17th edition, 2018. PP: 408. – Speroff’s Clinical Gynecologic Endocrinology & Infertility: Hugh Taylor, Lubna Pal, Emre Seli - Wolters Kluwer Publication - 9th edition, 2020. PP: – The John Hopkins Manual of Gynecology and Obstetrics: Betty Chou, Jessica L Bienstock, Androw J Stain - Wolters Kluwer Publication - 6th edition, 2021. PP: 603 Thank You