Page 67 Complete Your CE Test Online - Click Here 3, according to the severity of cell changes and the percent of the epithelium replaced by abnormal cells. CIN 3 is a reasonably standard diagnosis, and it is known to have about a 30% risk of developing into invasive cancer over many years if untreated [127]. CIN 2 has more variable outcomes over time [64]. CIN 3 is better understood and therefore a better endpoint for clinical trials, while CIN 2 serves as a threshold for treatment, to provide an extra measure of safety for the patient [150]. HPV testing HPV testing looks only for carcinogenic HPV strains [184]. HPV infection is linked to nearly all cases of cervical cancer. Approximately 15 cancer-associated (high-risk or carcinogenic) HPV genotypes cause virtually all cases of cervical cancer and precursor lesions of CIN 2 and CIN 3. Carcinogenic HPV infections are very common, particularly in young women, and most clear without treatment within one to two years. Screening with HPV DNA or HPV RNA testing also detects high-grade cervical dysplasia, a precursor lesion for cervical cancer. But a positive HPV test alone does not mean that cervical cancer or premalignant disease will develop; in one study, nearly 87% of women with positive HPV tests had no problem even after more than ten years of follow-up [74]. Additional clinical trials show that HPV testing is superior to other cervical cancer screening strategies, even though it identifies numerous infections that will not lead to cervical dysplasia or cervical cancer, especially in women younger than 30 years, in whom rates of HPV infection may be higher. Because a positive HPV test calls for a colposcopy, there is a risk of harm in younger women who have HPV but have not had a chance to clear the infection. In April 2014, the U.S. Food and Drug Administration approved an HPV DNA test that can be used alone for the primary screening of cervical cancer risk in women aged 25 years and older [150]. Co-testing with Pap and HPV DNA Screening every five years with the Pap test and the HPV DNA test (co-testing) in women 30 years and older is more sensitive in detecting cervical abnormalities, compared with the Pap alone. This also means more false positive tests, which require extra testing. Screening with the Pap plus HPV DNA test reduces the incidence of cervical cancer. HPV-based screening provides 60-70% greater protection against invasive cervical carcinoma, compared with cytology (Pap) alone [150,250]. Liquid-based cytology testing Newer techniques that employ liquid-based cytology (such as ThinPrep) are intended to improve the sensitivity of screening. As with the Pap, the optimal studies to determine the sensitivity and specificity of liquid-based cytology have not been done. Some studies showed sensitivity was modestly higher for detecting any degree of cervical intraepithelial neoplasia (CIN), with somewhat lower specificity, but these studies had weaknesses that rendered their findings uncertain. One study that was done more carefully showed that conventional Pap testing was slightly more sensitive and specific than liquid-based cytology [77,150]. The evidence is also mixed about whether liquid-based techniques improve rates of test adequacy. One advantage of liquid-based cytology is that HPV testing can be done on the same preparation if needed, but the liquid-based approaches cost more than conventional Pap testing. No study has yet examined whether liquid-based cytology actually reduces the number of women dying of cervical cancer compared with conventional Pap testing [150]. Women at higher-than-average risk of cervical cancer Depending on medical history, some women may need more frequent or additional screening for cervical cancer than the above guidelines. For example, women who [201]: ● ● Are HIV infected (HIV-positive, whether or AIDS has developed). ● ● Have a weakened immune system. ● ● Were exposed in utero to diethylstilbestrol (DES), which was once prescribed to pregnant women. ● ● Had a recent abnormal Pap test or biopsy result. ● ● Have had cervical cancer. Screening a woman without a cervix Based on solid evidence, screening is not helpful in women of average risk who do not have a cervix as a result of a hysterectomy for a benign condition. No study has shown that screening for vaginal cancer reduces mortality from this rare condition. Among women without cervices, fewer than one in every 1000 patients had abnormal Pap test results [150]. If a woman had a hysterectomy because of DES exposure, cancer, or other high-risk condition, this does not apply. Not recommended: Other screening tests The National Cancer Institute lists a number of tests that are unproven or that have evidence against them for cancer screening: ● ● Alpha-fetoprotein blood test (AFP): The AFP test is sometimes used, along with ultrasound of the liver, to try to detect liver cancer early in people at high risk of the liver cancer. The reported sensitivity of AFP for detecting HCC varies widely in both hepatitis B virus (HBV)-positive and HBV-negative populations, which is attributable to overlap between study designs. When AFP is used for screening of high-risk populations, a sensitivity of 39-97%, a specificity of 76-95%, and a positive predictive value (PPV) of 9-32% have been reported. It is important to know that AFP is not specific for HCC. Titers also rise in acute or chronic hepatitis, in pregnancy, and in the presence of germ cell tumors [173,191]. ● ● CA-125 test: This blood test, which is often conducted along with a transvaginal ultrasound, may be used to try to detect ovarian cancer early, especially in women with an increased risk of the disease. Although this test can help in diagnosing ovarian cancer in women who have symptoms and can be used to evaluate the recurrence of cancer in women previously diagnosed with the disease, there is evidence that it is not effective as an ovarian cancer screening test [191]. The NCI reported on a randomized controlled trial in which the ovarian cancer mortality rate was 3.1 deaths per 10,000 women in the screened group and 2.6 deaths per 10,000 person-years in the usual-care group. Of screened women, 9.6% had false-positive results that resulted in 6.2% undergoing surgery [183,191]. ● ● Regular breast self-exams: The NCI reports that routine self- breast examination (SBE) has not been shown in randomized controlled clinical trials to reduce deaths from breast cancer [191]. Based on solid evidence, formal instruction and encouragement to perform SBE leads to more breast biopsies and diagnosis of more benign breast lesions. The biopsy rate was nearly twice as high (1.8%) among the study population compared to the control group (1.0%) [142]. But monthly SBE is different from breast self- awareness, and it is important for any woman (or man) to know that if there is a lump or other unusual change in the breast, it should be checked right away. ● ● Clinical breast exams: The current evidence is insufficient to assess the additional benefits and harms of clinical breast exam (CBE; examination by a health care provider) [191]. The one randomized controlled trial, the Canadian National Breast Screening Study (NBSS), compared high-quality CBE by nurse- examiners with CBE plus screening mammography. It showed equivalent benefit for both modalities, but accuracy of CBE in the community setting might be lower than in the NBSS [46,142].