SCREENING & PREVENTION OF CANCER CERVIX Presentor : Dr. Kaushik Pandit, PGT, O&G Moderator: Dr. Sanghamitra Das, Assistant Professor, O&G
INTRODUCTION Carcinoma cervix is the commonest gynecological cancer in women worldwide It is the most common cause of cancer deaths in women in developing countries 70% of cervical cancers in India are diagnosed in late stages (Stage III & above) Cervical cancer is a preventable cancer and has a long duration of natural progression. Hence, prevention and screening become so important.
OUTLINE OF TODAY’S DISCUSSION PREVENTION Avoidance of high-risk factors HPV vaccination SCREENING Cervical cytology PAP smear Liquid based cytology Visual inspection screening of cervix HPV testing Colposcopy
PREVENTION OF CARCINOMA CERVIX
PRIMARY PREVENTION OF CARCINOMA CERVIX It targets prevention of HPV infection and epidemiological factors causing cervical cancer It includes: Health education and awareness against high-risk factors HPV vaccination
Table: Risk factors of Ca Cervix
HPV vaccination Vaccination against oncogenic HPV strains can prevent most cervical cancers Also help in prevention of vaginal, vulvar, anal, penile and nasopharyngeal cancers Vaccines contain synthetic L1 capsid proteins of each HPV type made through recombinant technology Thus, the vaccines are highly immunogenic but not infectious
CERVARIX Bivalent vaccine Against HPV 16 & 18 Prevents CIN & Cervical Cancer GARDASIL Quadrivalent vaccine Against HPV 6, 11, 16 & 18 Additionally prevents most genital warts caused by HPV 6 & 11 GARDASIL-9 Protects against 9 HPV strains ( 6, 11, 16, 18, 31, 33, 45, 52 and 58 ) Increases protection against cervical cancer by 80% More expensive, recently available in India
VACCINATION SCHEDULE Licensed for use from 9 yrs - 45 yrs For girls before their 15 th birthday: 2 doses, 6 months apart (0,6) For girls after their 15 th birthday: 3 doses (0, 1, 6) Intramuscular route EFFICACY Most effective if given before their first sexual contact Among girls previously not exposed to the virus, efficacy is around 99% In women already exposed to the virus, efficacy is about 44% Protective effect lasts for at least 8 yrs (possibly much longer)
NEWER UPCOMING HPV VACCINES CERVAVAC Developed by Serum Institute of India Target age group: 9-26 yrs Quadrivalent vaccine ( against HPV 6, 11, 16, 18 ) Intramuscular, 2 dose ( 0, 6-12 months ) WALRINVAX Developed by China Bivalent vaccine ( HPV 16, 18 ) CECOLIN Also being developed by China Bivalent vaccine ( HPV 16, 18 )
SECONDARY PREVENTION OF CARCINOMA CERVIX Detection of cervical cancer in pre-invasive stage ( CIN 1, 2, 3 ) or early stage of disease when treatment is possible Done by routine cervical screening ( PAP smear and/or HPV testing ) TERTIARY PREVENTION OF CARCINOMA CERVIX Timely diagnosis and treatment of cervical cancer By radical surgery (in early stages) By chemo-radiation (in advanced stages) Also includes palliative care
SCREENING OF CIN & CERVICAL CANCER Has reduced mortality of cervical cancer by 70% in developed countries Helps to detect preinvasive lesions or early stage cervical cancer that can be treated successfully
SCREENING GUIDELINES FOR CIN ACOG has published guidelines on cervical cancer screening tests in 2019: Start the screening (PAP smear) at 21 years of age in all average risk women PAP smear is done every 3 years till 30 years of age Between 30-65 years , screening is done with cytology alone at 3 yearly intervals or by HPV testing every 5 years Women with HIV infection and immunosuppressive conditions should be screened annually Screening can be stopped at 65 years of age for women with adequate screening ( 3 consecutive negative PAP tests or 2 consecutive negative HPV tests in previous 10 years) Women with treatment of CIN 2, 3, AIS & CA Cervix should continue screening for 20 years after treatment Post-hysterectomy, 3 yearly vault smear is done for 20 years only if CIN/invasive cervical cancer were detected in histology specimen
SCREENING GUIDELINES FOR LOW RESOURCE SETTING In developing countries, WHO has recommended at least one smear at about 30 years of age for all women Alternatively, smears can be done once in every 10 years Ministry of Health and Family Welfare (MOHFW), in 2019, has recommended VIA ( Visual Inspection of Cervix with Acetic Acid ) once in 5 years in all women of India between 30-65 years of age
90-70-90 TARGETS WHO has outlined certain targets to be met by 2030 This program has 3 main pillars Vaccination of 90% of girls with HPV vaccine by the age of 15 Screening of 70% of women using a high performance test by the age of 35, and again by the age of 45 Tratment of 90% women with pre-cancer and 90% women with invasive cancer
STEPS OF PRE-SCREENING COUNSELLING : Location of the cervix in the woman’s body Cause of and risk factors for cervical cancer Importance of screening for cervical cancer The screening test and how it is performed Screening test results and their implications Further tests or procedures that the woman will have to undergo if the test result is positive Available simple and safe treatment methods, if required Importance of follow-up visits even after treatment If the test result is negative, it is important that the test is repeated at regular intervals as advised, to prevent cervical cancer.
PAP SMEAR/ PAP TEST( Papanicolaou test) PRE-REQUISITES Done in postmenstrual phase Abstinence of 48 hrs No douching/vaginal tampon/intravaginal cream for 24-48 hrs PROCEDURE Position: Dorsal lithotomy Bivalve Cusco’s speculum used to expose complete cervix Devices used: Ayre’s wooden spatula/ Cytobrush / Plastic broom Sampling of Transformation zone at Squamo -columnar junction is mandatory for sensitivity of PAP test
The Ayre’s spatula is placed on the ectocervix The cervix is scraped by at least one full circle (360 degees once) It samples the squamocolumnar junction Fig. Ayre’s spatula & its use
Cytobrush collects endocervical sample Cytobrush is introduced into endocervical canal Such that outermost bristles are still visible at external os The brush is rotated by one-quarter turn Fig. Cytobrush & its use
PAP smear/ PAP test …contd. The spatula sample is quickly spread as evenly as possible over one-half to 2/3 rd of glass slide The endocervical brush is firmly rolled over remaining area of the slide The slide is quickly fixed by immersing it in Coplin’s jar Which contains 95% ethyl alcohol Stained using Papanicolaou’s stain at cytology department Fig. Coplin’s jar/ PAP jar
LIQUID BASED CYTOLOGY Here, liquid based medium is used to collect and preserve the cervical cytology cells Advantage over PAP smear : to decrease rates of inadequate cytology Broom device is used for liquid based cytology 2 FDA approved tests are available: SURE PATH THIN PREP Fig. Sure Path
Broom device has: Longer central bristles that take endocervical sample Shorter lateral bristles that take ectocervical sample 5 rotations are made in one direction Tip is broken off into the liquid medium Fig. Plastic broom and its use in liquid based cytology Fig. Slide for Liquid based cytology
VISUAL INSPECTION SCREENING OF CERVIX Visual Inspection with Acetic Acid (VIA) Visual Inspection with Acetic Acid with Low Level Magnification (VIAM) With hand held magnifying glass Visual Inspection with Lugol’s Iodine(VILI) Cervicography 2 photographs of cervix are taken before & after local application of 3-5% acetic acid Speculoscopy and Spectroscopy methods Uses laser induced fluorescence Still in experimental stage
VISUAL INSPECTION WITH ACETIC ACID (VIA) 3-5% acetic acid is applied to cervix and examined after 1 minute Acetic acid causes dehydration of cervical cells and coagulation of proteins into white precipitates Positive VIA is defined as presence of well defined acetowhite area on acetic acid application Positive VIA is indicative of: High Squamous Intraepithelial Lesion(HSIL) Early stage cervical cancer Fig. Presence of well defined acetowhite area on acetic acid application
VISUAL INSPECTION WITH LUGOL’S IODINE (VILI) Schiller’s or Lugol’s Iodine(5%) is applied to the cervix and immediately examined Normal squamous epithelium of cervix contains abundant glycogen and stains dark mahogany brown Abnormal epithelium ( CIN / invasive cancer ) contains little glycogen, doesn’t take iodine and remain unstained or stains mustard yellow Fig. VILI showing normal epithelium staining dark mahogany brown and abnormal epithelium staining mustard yellow
HPV TESTING Uses polymerase chain reaction to amplify viral DNA HPV DNA Testing is most effective in women more than 30 years Nowadays, HPV tests are used for primary screening for cervical cancer After the age of 30 yrs At an interval of every 5 yrs The combination of HPV testing with cytology ( CO-TESTING ) raises the sensitivity of a single screening test for high-grade neoplasia Leads to earlier detection and management of HSIL
INDICATIONS OF HPV TESTING : As primary screening for cervical cancer Women with cervical smear showing ASCUS (abnormal squamous cells of undetermined significance) As test of cure after 6 months of treating preinvasive lesions or glandular lesions ADVANTAGE OF HPV TESTING OVER PAP SMEAR : Higher sensitivity(>90%) Easier technical interpretation & high reproducibility DISADVANTAGE OF HPV TESTING : Most women with HPV positive results may represent transient HPV infections
INTERPRETATION (REPORTING) OF CERVICAL CYTOLOGY: THE BETHESDA SYSTEM Introduced for uniform reporting of results and nomenclature of cervical cytology Source: Williams Gynecology 4 th edition
For most abnormalities, colposcopy is recommended INTERPRETATION (REPORTING) OF CERVICAL CYTOLOGY: THE BETHESDA SYSTEM Source: Williams Gynecology 4 th edition
Source : Jeffcoate’s Principles of Gynaecology (8 th edition)
COLPOSCOPY It is the procedure of visualisation of cervix and lower genital tract under magnification with a colposcope Colposcope is an out-patient binocular magnification system with a light source Aim of colposcopy: Identify pre-invasive and invasive neoplastic lesions for directed biopsy Planning for subsequent management as per biopsy report Sensitivity = 50-80%
Fig. Colposcope
INDICATIONS OF COLPOSCOPY : Abnormal cervical cytology Follow-up of patients treated for CIN 2/3 or AIS(adenocarcinoma in situ) Unsatisfactory cervical cytology due to unexplained inflammation Unexplained cervico -vaginal discharge Unexplained abnormal lower genital tract bleeding History of lower genital tract neoplasia Post-treatment surveillance of lower genital tract carcinoma HPV 16/18 positive patients Persistent positivity of HPV infection VIA positive patients
Source : Williams Gynecology (4 th edition)
PROCEDURE OF COLPOSCOPY : Cervix is seen with colposcope Character of surface vessels is noted by application of a green filter (green filter enhances visualisation of blood vessels which appear darker) Acetic acid (3-5%) is then applied on the cervix It is a m ucolytic agent Causes reversible clumping of nuclear chromatin Makes neoplastic lesions to appear acetowhite Lugol’s iodine can also be used Colposcopy directed biopsy can then be taken from acetowhite areas or Lugol’s unstained areas
Fig. Procedure of Colposcopy
INTERPRETATION OF COLPOSCOPY Normal squamous epithelium is pink, smooth and transclucent Normal columnar eopithelium is reddish and velvety In normal colposcopy, there is no acetowhite area or other abnormal patterns Fig. Normal colposcopic findings
Fig. Normal colposcopic findings
ABNORMALITIES IN COLPOSCOPY ACETOWHITE EPITHELIUM : White coloured areas on cervix after acetic acid application CIN 1 : flat, pale acetowhite epithelium with feathery margins CIN 2,3(HSIL) : dense acetowhite epithelium with sharp, regular margins or elevated surface Fig. Acetowhite epithelium on colposcopy
ABNORMALITIES IN COLPOSCOPY PUNCTATIONS : Dilated capillaries in CIN terminate on the surface of epithelium and are prominent CIN 1 : punctations are fine HSIL : coarse punctations Fig. Fine punctations Fig. Coarse punctations
ABNORMALITIES IN COLPOSCOPY MOSAIC PATTERN : Terminal capillaries surrounding the acetowhite epithelium crowd together to give mosaic tile appearance Low grade lesions : smooth and fine mosaic High grade lesions : coarse mosaic pattern Fig. Mosaic pattern
ABNORMALITIES IN COLPOSCOPY ABNORMAL VESSELS : Atypical vessels are: Irregular in calibre Branching Appear as wide hair-pins Easily bleed on touch Indicative of invasive cancer Fig. Abnormal vessels
COLPOSCOPY DIRECTED BIOPSY From the abnormal areas on cervix visualised on colposcopy, directed biopsy can be taken with Tischler’s forceps Cervical punch biopsy forceps The biopsy specimen is sent for histopathological examination in 10% formalin solution (preserves morphology of the tissue) Fig. Cervical punch biopsy forceps
TAKE HOME MESSAGE Cervical cancer screening should be continued as per guideline even after vaccination
REFERENCES : Williams Gynecology 4 th edition Jeffcoate’s Principles of Gynaecology 8 th edition J.B. Sharma Textbook of Gynecology 2 nd edition Aggarwal S, Agarwal P, Singh AK: Human papilloma virus vaccines: A comprehensive narrative review: Cancer Treatment and Research Communications: Volume 37 , 2023, 100780