**4. Cervical cancer screening in developed countries**

In the U.S. there have been marked reductions in cervical cancer incidence and mortality over the past 60 years, largely the result of the development and widespread introduction of the Papanicolau (Pap) test in 1949 (Sawaya 1999; van der Graaf et al. 1986; Eddy 1990), based on cytologic examination of cells obtained from the cervix with a simple scraping using a wooden spatula or brush. It is estimated that 60% of the women who are diagnosed with ICC have never had cervical cytology testing or have not been screened within the 5 years

Cervical Cancer Screening and Prevention for HIV-Infected Women in the Developing World 237

detection of CIN 2 or higher of 100% (Kirby et al. 2004) and the other study reported a sensitivity of only 50% for detecting high-grade CIN (Massad et al. 2004). Currently CDC and ACOG do not recommend HPV testing for triage of HIV-infected women with abnormal cytology results, for follow-up after treatment for CIN, or to lengthen screening intervals (CDC 2009; ACOG 2010). A study examining HPV DNA testing as a primary screening method for cervical dysplasia in 94 HIV-positive women found that HPV DNA testing identified high-grade cervical dysplasia more accurately than Pap smear (Petry

Even in locations with high resources, screening for cervical dysplasia in the setting of HIV can be challenging. Women receiving gynecologic and primary HIV care at the same location are more likely to have had Pap smear screening within the previous year (AHRQ 2010). However, despite high rates of HPV and CIN, many women with HIV do not engage

Cervical cancer screening is often simply not available in developing world settings. Barriers to cytology-based screening programs include poor health infrastructure, lack of trained cytology technicians and cytopathologists and cost. In addition Pap smears are not point-ofcare tests; they require the ability to notify women of abnormal results and to follow-up with further evaluation or treatment. However, in low resource settings, many or most women reside at some distance from health centers, have little access to or cannot afford effective transportation, and there is a lack of effective recall mechanisms for abnormal results (Anorlu 2008). In sub-Saharan Africa there was a 60-80% default rate among those

Prevention of cervical cancer by identification and treatment of cervical cancer precursors is key, since treatment resources for invasive disease are scarce. In 2002, the survival rate for invasive cervical cancer was 21% in sub-Saharan Africa vs. 70% in US (Parkin et al. 2005). This is related to the fact that most patients present at late stages, as well as a lack of effective treatment resources, including surgical expertise and radiotherapy (Ashraf 2003). When women present with advanced cervical cancer, palliative care resources are also limited; although morphine is on the WHO list of essential medications (http://whqlibdoc.who.int/hq/2011/a95053\_eng.pdf), one study of 47 African countries

Recent work has focused on service delivery models using alternatives to cytology for screening for cervical precancerous lesions in order to improve access to safe and effective treatment, minimize loss to follow-up and prioritize utilization of specialized care. Necessary programmatic components, regardless of the strategy employed, include leadership at national levels making preventing cervical cancer a priority and including development of strategies and guidelines; community awareness building; training of providers and continuing education; data collection systems and outcomes monitoring, including quality assurance measures; administrative management; patient recall and retention plans; and appropriate linkages to assure adequate supplies, timely and high quality laboratory testing, and referrals when needed for higher levels of care. In South Africa, where it is estimated that 1 in 26 women develop cervical cancer in their lifetime, a cervical screening program was initiated in 2001; it called for three free Pap smears, starting

in the recommended annual Pap testing (Tello et al. 2008; Oster et al. 2009).

**4.1 Cervical cancer screening in low resource countries** 

found that only 11 used morphine for chronic pain (Harding 2005).

with cytologic abnormalities-(Cronje 2004).

1999).

before diagnosis (NIH 1996). However, conventional Pap smears are not perfect: a single Pap smear is associated with false-negative rates of 10–25%, largely because of errors in sampling or interpretation. False-negative Pap smears are associated with 30% of the new cases of cervical cancer each year (NIH 1996; Shingleton et al. 1995)

Newer Pap smear screening techniques using liquid-based media appear to decrease inadequate smears and also offer the possibility of direct HPV-DNA testing on collected specimens (ACOG 2009). A recent review of over 400 HIV-infected women who underwent both conventional and liquid-based cytologic screening found a significant decrease in the proportion of smears diagnosed as ASCUS/AGUS as well as the ASCUS/SIL ratio, with liquid-based preparations (Swierczynski 2002). HPV testing for cancer-associated HPV subtypes is currently used as a triage test to stratify risk in women with a cytology diagnosis of atypical squamous cells of undetermined significance (ASC-US), in postmenopausal women with a cytology diagnosis of LSIL and is also often used as an adjunct to cytology for primary screening in women older than 30 years (ACOG 2009). The currently used classification system for Pap smear results is known as the Bethesda classification, which includes an indication of adequacy of sample, whether the result is normal and, if abnormal, degree of abnormality (Solomon 2002).

With current US-based guidelines (ACOG 2009), Pap smears are recommended beginning at age 21 and every two years until age 30 if normal. After 30, if the last 3 tests have been normal, screening interval can be increased to 3 years. Providers may consider discontinuation of screening after age 65–70; if there have been no abnormal Pap smears in 10 years and no on-going risk factors. Colposcopy with biopsy of abnormal areas for histologic confirmation is recommended with ASCUS/+HPV or greater abnormality on Pap or with repetitive ASCUS, even if HPV-. The results of both Pap smear and colposcopy/biopsy are used to determine need to treatment, follow-up or further evaluation.

Women with HIV infection are recommended to have more frequent screening with cervical cytology: twice in the first year after diagnosis of HIV and, if normal, annually thereafter (CDC 2009; ACOG 2010) More frequent Pap smears should be considered with previous abnormal Pap smears, with conservative follow-up of cervical dysplasia without treatment (after colposcopic evaluation to rule out HSIL), with other evidence of HPV infection and after treatment for cervical dysplasia (Anderson 2005).

The role of HPV-DNA testing in HIV+ women is unclear. In a WIHS substudy of HIV+ and HIV- women with normal baseline cytology, incidence of squamous intraepithelial lesions (SIL) were examined by baseline HPV DNA results and stratified by CD4 count. Through 3 year follow-up, incidence of any SIL was similar in HIV- and HIV+ with CD4>500 who had negative results for oncogenic HPV or all HPV, suggesting that similar cervical cancer screening practices may be applicable to both groups. On the other hand, after just 2 years follow-up, incidence of any SIL in HIV+ with CD4<500 was increased over HIV-, even among women with negative results for any HPV, suggesting that a closer screening strategy may be needed for women with lower CD4 counts (Harris et al. 1995). In two prospective studies of HIV-infected women with ASC-US, approximately 30% of participants had evidence of oncogenic HPV, a finding that would support the use of HPV testing in this population if HPV testing remained highly sensitive (Massad et al. 2004; Kirby et al. 2004). However, one of these studies reported a sensitivity of HPV testing for the detection of CIN 2 or higher of 100% (Kirby et al. 2004) and the other study reported a sensitivity of only 50% for detecting high-grade CIN (Massad et al. 2004). Currently CDC and ACOG do not recommend HPV testing for triage of HIV-infected women with abnormal cytology results, for follow-up after treatment for CIN, or to lengthen screening intervals (CDC 2009; ACOG 2010). A study examining HPV DNA testing as a primary screening method for cervical dysplasia in 94 HIV-positive women found that HPV DNA testing identified high-grade cervical dysplasia more accurately than Pap smear (Petry 1999).

Even in locations with high resources, screening for cervical dysplasia in the setting of HIV can be challenging. Women receiving gynecologic and primary HIV care at the same location are more likely to have had Pap smear screening within the previous year (AHRQ 2010). However, despite high rates of HPV and CIN, many women with HIV do not engage in the recommended annual Pap testing (Tello et al. 2008; Oster et al. 2009).
