Nearly one in five HIV-infected women screened in our study had cytological evidence of squamous cell carcinoma and one in three had cytological evidence suggestive of HSIL. This high prevalence (>50%) of such severe cytologic abnormalities in women immunocompromised by HIV is particularly alarming given the fact that approximately 12-30% of immunocompetent HIV-negative women with untreated HSIL are known to progress to invasive cancer [17
]. These results indicate the crucial importance of screening HIV-infected women who live in resource-constrained settings, like those in Zambia, who are now accessing antiretroviral therapy. The availability of cost-effective screening and treatment for women who live in these environments is critical to reducing the morbidity and mortality associated with cervical cancer.
Of the numerous cervical cancer screening studies that have been performed among HIV-infected women in industrialized settings, most have found significantly higher rates of preinvasive disease when compared to HIV-negative women [10
]. In a review of cervical cytology in HIV-infected women residing in such environments, the overall reported prevalence of abnormalities ranged from 6% to 32%, with that of low-grade lesions ranging from 11% to 19% and high-grade lesions from 7% to 15% [46
]. In the same review, prevalence rates of abnormal cervical cytology in HIV-infected women were reported to be as high as 38% greater than those in HIV-negative women.
In general, most studies of cervical cytology among HIV-infected African women have been based on opportunistic screening studies involving women attending outpatient clinics for general medical care. Overall, screening results from such populations have revealed a 2- to 3-fold increased risk of cellular abnormalities, and from such diverse sub-Saharan African settings as Zimbabwe [25
], Kenya [27
], Senegal [29
], Malawi [31
], Rwanda [33
], Tanzania [34
], Zaire [35
], and South Africa [36 37
]. The highest rates of cellular abnormalities reported to date from Africa have come from investigations of commercial sex workers in Zaire (27%) [35
] and STI clinic attendees in Senegal (43%) [29
]. In comparison, the overall abnormal cytology rate of 93.8% and ≥HSIL rate of 53.1% in our study are perhaps one of the highest reported in the literature for HIV-infected women.
The reasons for this high-prevalence could be partially attributed to the fact that the women in our study were severely immunosuppressed (median CD4+ count 165/μL). The participants were recruited from HIV-infected women attending the tertiary care hospital to receive antiretroviral therapy, and to be eligible for such treatment they had to meet the criteria of having a CD4+ count of <200/μL or have recently experienced some other AIDS defining illness. Although a majority of our study participants (78.2%) were already taking antiretroviral therapy, however, most had been taking it for less than 6 months. Nonetheless, settings such as Zambia will encounter increasingly high numbers of such immunosuppressed women who will now be accessing antiretroviral therapy. Providing cervical cancer screening and treatment services linked to HIV/AIDS care is one possible avenue to provide this much needed prevention intervention.
Another possible explanation for the high rate of severe cervical abnormalities detected in our study participants is the very high sensitivity of monolayer liquid cytology [38
], in comparison to conventional cytology used in previously cited studies. Also, because the cytological analysis was conducted in a sophisticated laboratory in the United States, it may not be representative of developing country settings. Nonetheless, it highlights the hitherto underestimated prevalence rate, mostly due to the lower sensitivity of conventional cytology [41
It is also important to note that most study participants were women living in marginalized circumstances of the society, that is, most were inhabitants of peri-urban “compounds” that are living quarters characterized by high unemployment rates, severe shortages of fresh water, poor housing, inadequate sewage, and high rates of infectious diseases. All of the above are widely prevalent conditions for the majority of HIV-infected women living in urban sub-Saharan African cities like Lusaka. These same socioeconomic conditions prevent them from accessing preventive and therapeutic clinical care, thereby increasing their vulnerability and putting them at double jeopardy for both HIV/AIDS and cervical cancer.
As seen in our results, the risk of severe cytological abnormalities was highest around the median age of our participants (36 years) with a downward trend both above and below the median (). Because our sample was highly representative of HIV-infected women seeking antiretroviral therapy in the public sector clinics in Zambia, it strongly suggests the critical need for undertaking a concerted effort towards the provision of a cervical cancer screening and treatment program that benefits the average woman accessing these clinics.
Presence of high-risk HPV was an independent predictor of HSIL and SCC on multivariable modeling. These findings confirm the need for exploring the use of alternative screening methods like HPV testing in conjunction with cytology or low-cost visual inspection based methods, as a triage tool for the better management and adequate referral of these women to colposcopy and/or treatment. The use of HPV testing among HIV-infected women has been controversial [43
]; however, the use of HPV testing in this high-risk population may offer better outcomes if cost of testing falls within the range of donor-funded or government supported activities. The crucial importance of investigations to study the natural history of HPV-induced cervical neoplasia and the impact of antiretroviral therapy on the natural history of cervical neoplasia in these women is also highlighted through the findings of this preliminary study.
Bilateral and multilateral donor assistance programs (e.g., Presidents Emergency Plan for AIDS Relief, Global Fund) are improving the availability of antiretroviral therapy in resource-constrained settings [8
]. The findings in this report highlight the importance of linking cervical cancer prevention services for HIV-infected women to antiretroviral therapy programs. By so doing, we have the opportunity to reduce the burden of both HIV and cervical cancer in impoverished settings where both diseases are most prevalent.