Dr Kirtan Krishna MS , DNB, Fellowship in Fetal Medicine Assistant Professor, OBG - PESIMSR , Kuppam Consultant Fetal Medicine – Cloud 9 hospitals, Bangalore

PAP SMEAR Dr. Kirtan Krishna

SECONDARY PREVENTION Screening may help in early detection of cervical abnormalities

Community low resource settings Tests Available Visual Inspection VIA VILI Pap Smear Conventional LBC HPV DNA Testing Cervicography Pap Net Polar Probe Community low resource settings Still Experimental

PAP SMEAR PAP smear sampling of cervix involves scraping of cervical surface and a portion of non visualised cervical canal using various sampling devices

Cervical cancers and cervical pre-cancers are classified into 2 main types of cervical cancer: squamous cell carcinoma and adenocarcinoma. About 80% to 90% of cervical cancers are squamous cell carcinomas.

Making pap smear more accurate Try not to schedule an appointment for a time during the menses. The best time is at least 5 days after the menses stops. Don't use tampons, birth-control foams or jellies, other vaginal creams, moisturizers, or lubricants, or vaginal medicines for 2 to 3 days before the test. Don't douche for 2 to 3 days before the test. Avoid sexual intercourse for 2 days before the test.

HOW TO TAKE A PAP SMEAR ? Spatula is rotated through 360 degrees maintaining contact with ectocervix Do not use too much force [bleeding /pain] Do not use too less force [inadequate sample] Sample is smeared evenly on the slide and fixed immediately Both sides of spatula are to be smeared

HOW TO TAKE A PAP SMEAR ? Endocervical sample is collected using an endocervical brush Insert the cytobrush into canal, so that last bristles of brush are visible Rotate the brush through 180 degrees. [more rotations increase the chance of bleeding] Sample is rolled on the slide and fixed.

FIXATION OF SMEAR Fixation is done immediately with fixative like 95% alcohol or cytofix spray to avoid air drying Spray should be kept at 10 - 12 inches, to avoid destruction of cells by propellent in the spray Smear should monolayer for proper penetration of cell surface by fixative

Liquid based cytology Insert the cytobrush into canal, so that last bristles of brush are visible Rotate the brush through 180 degrees. [more rotations increase the chance of bleeding] Detach the brush and immerse in the liquid(alcohol)

There is no evidence that LBC improves the accuracy of screening Advantages of technique LBC is semi-automated It creates a uniform spread of epithelial cells that are easier to read by cytotechnicians and cytopathologists reduces the rate of unsatisfactory samples. The LBC sample may also be used for reflex testing for HPV DNA and other biomarkers like chlamydia at a later date Several slides can be prepared from one smear

SCREENING GUIDELINES

American cancer society(ACS) American society for colposcopy and cervical pathology (ASCCP) and American society for clinical pathology(ASCP)2012 U.S. Preventive Services Task Force (USPSTF) 2012 American colloege of Ostetricians and Gynacologists (ACOG) Society of Gynaecological Oncology (SGO)and the American society for colposcopy and cervical pathology (ASCCP) :Interim clinicalguidance for primary hr HPV testing 2015 When to start screening Age 21 . Women aged < 21 years should not be screened regardless of age of sexual initiation or other risk factors Age 21(A recommendation) Recommend against screening woman aged < 21years ( D recommendation) Age 21 regardless of the age of onset of sexual activity .Women aged < 21 years should not be screened regardless of age of sexual initiation and other behaviour relatedrisk factors ( Level A evidence) Refer to major guidelines

Screening method and intervals Cytology (conventional or liquid based) 21- 29 yrs 30-65yrs Every 3years Every 3 years Every 3yrs Every 3 yrs Not addressed HPV co – test (cytology+ HPV test administered together) HPV co testing should not be used for women aged <30 years(D) Every 5 years HPV co testing should not be usd for women aged <30 years(D) Every 5 years(A) HPV co testing should not be used for women aged <30 years(A) Primary hr HPV testing( as an alternative to cotesting or cytology alone ) For women aged 30- 65 years , screening by hpv testing alone is not recommended in most clinical settings Every 3 years . Recommend against primary hr HPV screening in women aged <25 years of age .

American cancer society(ACS) American society for colposcopy and cervical pathology (ASCCP) and American society for clinical pathology(ASCP)2012 U.S. Preventive Services Task Force (USPSTF) 2012 American colloege of Ostetricians and Gynacologists (ACOG) Society of Gynaecological Oncology (SGO)and the American society for colposcopy and cervical pathology (ASCCP) :Interim clinicalguidance for primary hr HPV testing 2015 When to stop screening Aged >65 years with adequate negative prior screening and no history of CIN 2 or higher within the last 20 years . (Adequate negative prior screening results are defined as 3 consecutive negative cytology prior 2 negative co test within previous 10 years , with the recent test performed within 5 years) Aged >65 years with adequate screening history and are not otherwise at high risk for cervical cancer(D) Aged >65years with adequate negative prior screening results and no history of CIN2 or higher(A) Not addressed

NHS In the UK, the NHS Cervical Screening Programme screens: women between 25 and 49 years every 3 years women between 49 and 64 years every 5 years.

WHO guidelines 2013 Age at initiation – 30 yrs 30 – 49 yrs Screening even once in a lifetime would be beneficial. Screening intervals may depend on financial, infrastructural, and other resources 3 screening tests – HPV preferrable, VIA & treat, cytology f/b colposcopy

National Guideline Three (3) smears per lifetime, with a 10-year interval between each smear, commencing at not earlier than age 30 years. LSIL and ASCUS: repeat the smear in 12 months’ time - If the diagnosis remains the same or worsens, refer for colposcopy If negative on the second smear - normal screening cycle. HSIL and AGUS: refer to a colposcopy. If negative on colposcopy and cytology, the client can be discharged. If positive, treat.

A positive HPV test does not mean that a woman has cancer. WHAT IS THE HPV TEST? The HPV test is a very accurate way to tell if high-risk HPV is present in a woman’s cervix. This test can use the same sample of cells taken for the Pap test. A positive test result means a woman has high-risk HPV. A positive HPV test does not mean that a woman has cancer.

HPV-based screening Large RCTs, such as the ARTISTIC in the UK and a recent meta-analysis - HPV-based screening 60-70% better protection against invasive cervical cancer when compared to conventional or liquid based cytology. It is expected that HPV-based screening will replace cytology-based screening, at least in women aged 30 or older.

Why no screening before 25yr? Due to the rarity of invasive disease in women below 25. HPV infection very common in younger age groups; the early identification of clinically insignificant lesions that are likely to regress - increase the risk of over-investigation and over-treatment - adversely impact reproductive outcomes

How Pap tests are reported

Features of dysplasia 1.enlarged cells with increased nucleocytoplasmic ratio. 2.Abnormal nucleus –in size,shape and number. 3.Irregularity of nuclear outline. 4.Hyperchromatic nuclei. 5.Condensation of chromatic material. 6.multinucleation.

MILD -nucleus occupies less than half of total area of cytoplasm -cells are of superficial/intermediate type. -nucleus occupies less than half of total area of cytoplasm

MODERATE Cells are of superficial,intermediate, parabasal type. nucleus-1/2 to 2/3 of cytoplasm.

SEVERE Cells are of basal type. Round,oval,polygonal or elongated –fibre cells with elongated tail of cytoplasm-tadpole cell

Unsatisfactory Smears Should be repeated in 2-4 months Papsmears which lack an endocervical component can be repeated in 1 year If any of the following risk factors present should be screened every 6 months -high risk HPV positivity -previous glandular abnormality -immunosupression -inability to visualize endocervical canal -non compliance -history of ascus or greater abnormalities in the past without three interval normal pap

Take home message Screening is more important than the method Universal sreening Start from 21 – 25 yrs, Every 3yrs upto 65 yrs or 5yrs with HPV co testing Inadequate smears repeat after 3 months Boderline smears repeat after 6 months Missing endocervical glandular cells – repeat after 1 yr