Dr Nurulhuda Samsudin O&G dept. SGH Introduction Cervical cancer is the 3rd most frequent cancer among Malaysian women. The National Cancer Registry in 2006 reported that the age standardized incidence (ASR) of cervical cancer was 12.2 per 100,000 women. The proportion of deaths due to cervical cancer among all forms of cancer deaths has been steadily increasing. In 1998, cervical cancer was ranked 8th as cause of deaths in Malaysia. By 2006, deaths due to cervical cancers was ranked 3rd . 12.2 deaths for every 100,000 women dying from any form of cancer was due to cervical cancer. (National Cancer Registry Malaysia, 2006) Preventable?-Yes This increase in morbidity and mortality due is unwarranted not only because: - The definitive cause of cervical cancer is now known i.e primarily due to high risk HPV infection. - The disease takes a long time to develop after initial infection. Unlike most other types of cancer, it is preventable when precursor lesions are detected and treated. Therefore, screening can reduce both the incidence and mortality of cervical cancer. Impact of cervical cytology screening on the incidence of invasive cervical cancer in the United States.In Kurman R (ed): Blavstein’s Pathology of the Female Genital Tract. 5th ed. New York, Springer-Verlag, 2002. Screening modalities: Natural history models A clear understanding of the natural history of cervical cancer is a key to planning and implementing a rationale screening programme. Risk factor for cervical cancer Genital infection with a high-risk HPV type. Early onset of sexual activity. Multiple sexual partners. Cigarette smoking. Immunocompromised. Low socioeconomic. 99.7% of all cervical cancer cases are associated with persistent infection with high-risk HPV types. HPV types 16 and 18 are the most common high-risk types and account for 70% of all cervical cancer cases worldwide. -50% as a result of HPV-16 infection . -20% as a result of HPV-18 infection. HPV DNA Detection Sampling of cells for cytology Visual inspection Screening-Cytology The mainstay of cervical cancer screening for the last 60 years has been the Papanicolaou test. The Papanicolaou test, also known as Pap smear, was developed in the 1940s by Georgios Papanikolaou. It involves exfoliating cells from the transformation zone of the cervix to enable examination of these cells microscopically for detection of cancerous or precancerous lesions. 1883-1962 The Transformation Zone The optimal Pap smear contains: Sufficient mature and metaplastic squamous cells to indicate adequate sampling from the whole of the transformation zone. Sufficient endocervical cells to indicate that: the upper limit of the transformation zone was sampled to provide a sample for screening of adenocarcinoma and its precursors When to Perform The best time is: Any time after the cessation of the period. Avoid smear-taking during menstruation. Avoid in the presence of obvious vaginal infection. Avoid within 48 hours of use of vaginal creams or pessaries or douching. Avoid within 24 hours of intercourse. Avoid lubrication or cleaning of cervix with preliminary pelvic examination. Good communication with the pathologist is essential. FORM How to perform Pap Smear Which Spatula? Choose the contoured end of the spatula that best conforms to the anatomy of the cervix and the location of the transformation zone The Report Bathesda System Liquid Based Cytology BD SurePath™ ThinPrep FDA Approved MonoPrep LBC vs Pap Test Increase in sensitivity up to 12% better for the detection of abnormalities of low-grade squamous intraepithelial lesions with LBC compared with the Pap smear. No difference between the specificity of LBC and Pap smear. The English pilot study showed a statistically significant decrease in the number of inadequate samples, from 9.1% with Pap slides to an average of 1.6% with LBC (87% reduction, p < 0.0001) Reduced the pressure on the workforce because of fewer inadequate and clearer to read samples. Reduced levels of anxiety in women because fewer need repeat tests and because they receive their results more quickly. Remnant cells may be use for additional test e.g HPV DNA testing. Visual Inspection Involves 3 different approaches: Visual inspection of cervix with acetic acid (VIA). Visual inspection with magnification (VIAM). Visual inspection after application of Lugol’s iodine (VILI). VIA Applying 3% to 5% acetic acid and apply to the cervix liberally. When acetic acid is applied to normal squamous epithelium, little coagulation occurs in the superficial cell layer, as this is sparsely nucleated. Areas of CIN and invasive cancer undergo maximal coagulation due to their higher content of nuclear protein (in view of the large number of undifferentiated cells contained in the epithelium). This prevent light from passing through the epithelium. As a result, the sub-epithelial vessel pattern is obliterated and the epithelium appears densely white. In CIN, acetowhite is restricted to the transformation zone close to the squamocolumnar junction, while in cancer it often involves the entire cervix. Test negative Test Postivie Suspicious for cancer VILI Lugol iodine is applied over the cervix. Squamous epithelium contains glycogen, whereas precancerous lesions and invasive cancer contain little or no glycogen. Iodine is glycophilic and is taken up by the squamous epithelium, staining it mahogany brown or black. Columnar epithelium does not change color, as it has no glycogen. Immature metaplasia and inflammatory lesions are at most only partially glycogenated and, when stained, appear as scattered, ill-defined uptake areas. Precancerous lesions and invasive cancer do not take up iodine (as they lack glycogen) and appear as well-defined, thick, mustard or saffron yellow areas. Test Negative Test Positive Suspicious for cancer VIA vs VIAM vs VILI VILI has the highest specifity, detecting 75 per cent of all cases of HSIL compared with VIA and VIAM which detected less than two third of cases. VILI has higher sensitivity. The pooled sensitivity of VILI 91.8 per cent (range 76-97.3%) compared to those of VIA (76.9%) and VIAM (64.2%). The yellow colour changes associated with a positive VILI test result could be recognized with much greater ease by trained health workers compared with the acetowhite lesions associated with VIA. Management Offer to treat immediately, (without colposcopy or biopsy, known as the “test-and-treat” or “single-visit” approach). Refer for colposcopy and biopsy and then offer treatment if a precancerous lesion is confirmed. HPV Testing HPV cannot be grown in culture and detection of the virus relies on a variety of techniques used in immunology, serology, and molecular biology. 2 assays most widely used: PCR with generic primers The Hybrid Capture 2 assay. HPV DNA Testing – Hybrid Capture Assay The Hybrid Capture assay (hc2) is a batch test based on hybridization in a solution of long synthetic RNA probes. -Probe B is complementary to the genomic sequence of 13 high-risk types (HPV-16,-18, -31,-33, -35, -39, - 45, 51, -52, -56, -58, -59 and -68). -Probe A measures 5 low-risk (6, 11, 42,43,44) HPV types. HPV DNA analysis - Sampling Helthcare provider/Self sample Residual from LBC HPV DNA testing vs Cytology The HPV testing was: More sensitive in detecting CIN2+ than cytology (96.1% vs. 53.0%) Less specific (90.7% vs. 96.3%). Figure 1. A meta-analysis of seven primary HPV screening studies in six European countries investigated the negative predictability of screening tests. After three years, the incidence of CIN3 was about 5 per 1,000 for women who were negative for cytology tests. For women who were negative for HPV at baseline, by 72 months the incidence of CIN3 was about 2.5 per 1,000. Co-testing had marginally better predictability than HP Which Screening Modalities? Screening Guidelines – Who & Why? Screening Guidelines: HPV Testing – Who & When Prevalence of high-risk HPV and incident cases of cervical cancer in the U.S., 2003–2005. Surveillance Epidemiology and End Results (SEER) data for incident cases among females aged 15 to 19 years and 50 to 64 years ASCCP Guidelines Malaysian Screening Programme Guidelines Screening Guideline- Past, Current, Future Cervical cancer screening in Malaysia began in 1969, after the intergration of the family planning services into the Maternal and Child Health Program of the MOH. It has expanded across the country following the launching of the “Active Lifestyle” campaign, in 1995. In 1998 “National Pap Smear Screening Programme” was setup, it offers screening to all eligible women aged 20-65 years old for the first 2 years than 3 yearly is the result is normal. The agencies involved: National Population and Familly Development Board (LPPKN) University hospitals & Government Private clinics and hospitals. Military hospitals and other nongovernmental. NGOs Agencies such as Federation of Family Planning. Association of Malaysia and National Cancer Society. Current Pap smear screening services had been available for some time, nevertheless studies have shown that half of all women who died of cervical cancer did not undergo Pap smear in the past five years (Adeeb et al, 2008). Reported that no reduction in the prevalence of cervical cancer has been noted in the country. (Wong et al.2008) Improving our Screening Programme Review of current system. Empowering women. Informing and education.