Genital infection by human papillomavirus (HPV) is one of the most common sexually transmitted infections, known to be the cause of cervical cancer 123. Although HPV is known to be strongly associated with the development of cervical cancer, most HPV infections in young women are transient 4. Women with persistent infection appear to have a higher risk of developing significant cervical cancer 25. The burden of this infection on public health is compounded by the recognized causal relations between genital HPV infection and cervical dysplasia or cervical cancer 67. Although factors that influence persistence of HPV are not yet well understood, several studies suggest that alterations in cell mediated immune responses play a major role in persistence of HPV. The higher rates of HPV infection, high-grade squamous intraepithelial lesion (HSIL), and cervical cancer among immunosuppressed individuals, specifically HIV-infected women, underscore the importance of control of immune response in HPV infection. Studies on adult women have consistently shown that the prevalence of HPV infection and HSIL are higher among HIV infected women and that these differences are exaggerated among women with lower CD4+ cell counts 8910. Several recent prospective studies have documented that the rate of persistence of HPV among HIV-infected women is higher than that among non HIV-infected women 1112. Specific types of HPV are associated with cervical cancer, but whether these high-risk types have natural histories that are different from those of other types not associated with cervical cancer is unknown 1314. The modification of the viral markers may be the crucial factor of disequilibrium in the interaction between virus and host: an increased replicating capacity of the virus versus a reduced control mechanism of the immune system. In this context it's evident that in HIV-infected women, both viral and host factors conspire, as these patients have an impaired immune system usually more exposed to HPV infection. Some studies have also considered the impact on cervical pathology on HIV disease care, mainly represented by the introduction of highly active antiretroviral therapy (HAART), which through the substantial recovery of immune function has significantly changed the scenario regarding HIV-related pathologies such as opportunistic infections and cancers 1516. The objectives of this study were to compare rates of cervical abnormalities related to HPV infection among HIV-infected women with and without HAART initiation and to examine immunological and behavioural risk factors associated with persistence of HPV.

This study provides data on the risk of cervical cancer among HIV positive women less than 60 years old in the day care centre at Bonassama hospital Douala -Central Africa. The extent to which HIV increases the risk for cervical cancer is especially important in Cameroon referring to the epidemiology of the HIV especially among women. In our study, HIV positive women are at high risk of invasive cervical cancer. This could be due to the competing risk of mortality from other conditions associated with HIV/AIDS, particularly in a setting where antiretroviral therapy was not available at the time and for all patients. Our findings that HIV infected women were at a significantly higher risk of LSIL and HSIL confirm the results of studies carried out in both developed and other developing countries 717222324. The relative prevalence of SILs or cytological abnormalities among HIV positive women is higher than that ever been reported by any other study in Africa. Hawes et al. reported a cytological abnormality prevalence of 37% among women with HIV-1 infection attending an outpatients infectious disease clinic in Senegal 17, Yamada 27.1% in urban patients in Kenya 25, Moukassa 15.36% among urban dwellers in Congo 26.

A potential limitation of this current study is that cytological abnormalities were not histologically confirmed. However, it has been shown that the Pap smear sensitivity and specificity are similar among HIV negative and HIV positive women 27. We found an association between HAART and the stage of cervical pre-cancer. Our results are in agreement with others that have shown an association between HIV, HAART and cervical abnormalities [1516, and 28]. An additional limitation of our study is that complete information regarding the immunological status of patients has not been documented for all the groups. Similar of different studies by the same author [915162025, and 29] have reported that the severity of HIV-related immunodepression is associated with increased incidence of HPV infection and SILs. Data obtained from the current study further confirm these findings reported by other investigators of our geographic area 172223242526. Several studies suggested that markers of advanced HIV disease such as CD4+ T cell counts or HIV-RNA plasmatic levels are associated with increased risk of HPV infection and SIL 8172829. However some documentations and data have revealed that the relationship between HIV and HPV is more complex. Human immunodeficiency virus infection is associated with an increased transcriptional activity of early HPV genes. Studies on adult women have shown that HPV infection with both high-risk and low-risk HPV types is more likely to persist among HIV-infected women 812. Because they have more years of sexual activity, adult women may reflect a group of women further along in their history of HIV and HPV infection. Our data further support the important role played by CD4+ T cells 2829 in the control of HPV infection: the lower the CD4+ T cell count, the more likely that HPV infection will persist. Persistent infection in turn may increase the risk for the development and persistence of squamous intraepithelial lesions. In fact, women whose immunosuppression is related to infection with human immunodeficiency virus are at increased risk of infection with multiple types of HPV 28. In developed countries it's recommended for HIV positive women to have two cervical cytological assessments within the first year after HIV diagnosis and annually thereafter, referred for colposcopy for any smear showing an ASCUS (atypical squamous cells of undetermined significance) or more severe lesions 30. These guidelines are not feasible in settings with limited or poor resources. The high prevalence and risk of cervical abnormalities documented in our research projet underscores the importance of developing screening and management guidelines for HIV positive women. As antiretroviral therapy becomes increasingly available in Cameroon, the life expectancy of HIV positive women will increase as well. It's therefore important to conserve this invaluable benefit and avoid its upset by an increased risk in the development of cervical cancer. A cervical screening program is of critical importance as it informs local researchers on the natural history of cervical abnormalities, which might be recommended for HIV positive women. The STIs history of studied subjects revealed the presence of reproductive tract infection in patients with cervical cytology abnormality. This high rate of infection is attributed to the promiscuous sexual behaviour of the sampled women. Other studies suggest lack of hygiene, crowded or unsanitary living conditions, stress, and the presence of other sexually transmitted infections as factors that spread HPV infection and, eventually cervical cancer 30. In the current study, history of STI infections was a non significant risk predictor in distinguishing LSIL to HSIL positive cases.

HPV infection increased in accordance with lower CD4+ T cell counts and higher HIV RNA levels. High-grade lesions were strongly associated with high-risk HPV infection and low CD4+ T cell counts. Immunodeficiency as a result of HIV infection appears to be important for malignant progression within the cervix. Nationwide prevention of HIV infection and cervical cancer screening are necessary for the health of women in Cameroon. The increased public health burden enhanced by HPV is an important and gender-specific aspect of HIV infection. Guidelines on proper screening for cervical abnormalities in HIV positive women are urgently needed in Cameroon.

The authors declare that they have no competing interests.

KMML conceived the study, participated in its design and statistical analysis, coordinated and drafted the manuscript. GMLC participated in CD4 analysis using the flow cytometry, data collection and helped to draft the manuscript. DC participated in flow cytometry analysis, data collection and helped to draft the manuscript. WM participated in study design, clinical examination and recruitment of women at the study site and coordination. MA carried out cytology analysis. NNA participated in the study design, statistical analysis and helped to draft and review the manuscript.