Prevalence and Predictors of Cervical Cytological (Pap Smear) Abnormalities Among HIV-infected Women at the HIV Treatment Center of Jos University Teaching Hospital Jos, Nigeria.

We carried out a cross sectional study of adult women with HIV who presented for Pap smear test for the rst time at the Jos University Teaching Hospital, Jos, North Central Nigeria between November2018 and January 2020. Prevalence of abnormal cervical nding was reported in percentage and also expressed per 100 population of women. The effects of the characteristics of the women of the abnormal pap smear nding was determined using the logistic regression model where 95% condence interval and adjusted odds were used as point and interval estimates respectively while a probability value of < 0.05 was considered statistically signicant. in HIV- infected women and is associated with increasing age. Advocacy to institutionalize screening at earlier age is therefore key to improving dismal outcomes.


Introduction
Cervical cancer though preventable has continued to pose as a public health threat in sub-Saharan Africa. [1] According to WHO, 19 out of the top 20 countries worldwide with the highest burden of cervical cancer in 2018 were in Africa. [1] Ninety per cent of 311 000 cervical cancer deaths globally per year occur in lowand middle-income countries (LMICs), with the highest burden borne by sub-Sahara African countries that have the highest burden of Human Immunode ciency Virus (HIV). [2] HIV-positive women are at increased risk of human papillomavirus (HPV) infection and progression to invasive cervical cancer (ICC). [2] The likelihood that a woman living with HIV will develop invasive cervical cancer is up to ve times higher than for a woman who is not living with HIV. [2] Few diseases re ect global inequities as much as cancer of the cervix. In LMICs its incidence is nearly twice as high, and its death rates three times as high, compared with high income countries (HICs). [2,3] Proven and cost-effective measures for eliminating cervical cancer such as avoidance of risk factors, HPV vaccination, papanicolaou screening( pap smear) and treatment of precancerous lesions exist, but to date have not been widely implemented in regions of the world where the disease burden is highest. [2][3][4][5][6] In Nigeria as in other sub-Saharan African countries there is no organized screening program, and the few services available are only opportunistic with little or no impact. [7][8][9][10][11][12] Development of cervical cancer screening policy and institution of organized screening program targeted at covering ≥ 80% of population at risk is fundamental. [13][14][15] Though HIV care and treatment in countries worst hit by HIV epidemic has resulted in prolongation of life expectancy, cervical cancer in women living with HIV has not received the attention and resources that is needed to address its prevention and treatment. [16,19] We therefore sought to determine the prevalence and predictors of abnormal Pap smear ndings among a group of HIV-infected women accessing an opportunistic cervical cancer screening service newly established at the HIV treatment center in Jos, Nigeria.

Materials And Methods
Study design This is a cross-sectional descriptive study that was carried out among HIV-positive women who were attending the adult HIV clinic in Jos University Teaching Hospital (JUTH), Jos between November2018 and January 2020 .

Study Area
JUTH is a tertiary health institution located at Jos, Plateau state with a catchment area of the four states of the north-central geopolitical region of Nigeria. These are Benue, Nassarawa, Kaduna and Bauchi states. Plateau state is located in Nigeria's middle belt with an area of 26,899 square kilometers and an estimated population of about three million people in 2019. [20] Study Population The study population comprised HIV-positive women attending the HIV clinic in the hospital. All HIVpositive women attending the clinic were included while those with a history of cervical cancer, previously treated premalignant lesions of the cervix and those that were pregnant were excluded from the study.

Data Collection
De-identi ed data of HIV-positive women attending the adult HIV clinic in JUTH for the rst time was obtained from the secured electronic records of the clinic. The cervical Pap smear cytology screening outcomes were reported according to the Bethesda 2001 cytology reporting system. [21] The key dependent variable was the cervical cytology (Pap smear) screening outcomes. Data on sociodemographic and reproductive characteristics as well as clinical information such as nadir viral load and nadir CD4 counts were also obtained. The age, CD4 count and viral load were used as continuous variables while categorical variables were parity (0, 1-4, ≥ 5), age (≤ 43,>43), age at rst sexual debut (< 15, 15-18, ≥ 19), number of sexual partners (1, 2-4, ≥ 5) and use of contraception (used, not used).Viral load was further log transformed for analysis in view of the skewed nature of the measurement. Pap smear results was categorized into normal squamous intraepithelial lesion (SIL) and abnormal SIL while the abnormal SIL was further categorized into mild dysplasia and severe dysplasia. Abnormal SIL were ASCUS, ASC-H, LSIL, HSIL, and HSIL with suspicion of invasion and AGUS while mild dysplasia and severe dysplasia were ASCUS, AGUS, LSIL and ASC-H, HSIL, HSIL with suspicion of invasion respectively.

Data analysis
The data collected was analyzed with STATA software, version 14 college station (Stata Corporation, TX, USA; 1985). Continuous variables were expressed as means, medians, standard deviations and interquartile range and categorical variables as percentages and proportions. Logistic regression models were developed to explore the association of selected variables with cervical cytological outcomes among the women.
Three level of analysis were done. The rst level analysis was a descriptive analysis to determine the overall prevalence and pattern of cervical cytological abnormalities based on various sociodemographic and clinical characteristics of the women. Differences in proportions and means of observable measures between the cervical cytology outcomes were assessed using Chi-square test for proportions and t-test for difference of means.
The second level analysis was bivariate logistic regression analysis performed to assess the association between apriorically selected sociodemographic, clinical (viral load and CD4 count), reproductive characteristics and (1) cervical cytology results (normal and abnormal squamous intraepithelial lesion) (2) mild dysplasia (3) severe dysplasia. The third level analysis was a multivariate logistic regression analysis involving all the factors that were signi cantly associated with cervical cytology (Pap smear) results at the second level analysis. Box plots graphs of ages of these women by Pap smear results was plotted. P < 0.05 was considered as statistically signi cant. The results are presented as crude odds ratios (CORs) or adjusted odds ratios (AORs) and their 95% CI.

Methodology
We performed a cross sectional study of adult women with HIV who presented for Pap smear screening test at the Jos University Teaching Hospital, Jos, North Central Nigeria between November 2018 and January 2020. Prevalence of abnormal cervical nding was reported in percentage and also expressed per 100 population of women. Association between characteristics of the women and nding of pap smear screening was determined using logistic regression with 95% con dence interval and crude odd ratio used as interval and point estimates of the effect of the characteristics of the women on the outcome of the screening while a p -value of < 0.05 was considered statistical signi cant.

Discussion
Our results highlights the distribution of sociodemographic and clinical factors associated with morphologic cervical cytological ndings from an opportunistic Pap smear screening among adult HIV women managed in our HIV treatment center at Jos, Nigeria. We found that the median age and mean age at onset of screening was 43 years. [ Table 1] This is in variance to the 35 years reported from an earlier study done in the same hospital but at a different center that screens for the general population. [22] This might be due to the lower sample size in this study. Other similar studies in other centers in the region also report a lower mean age at rst screening. [23][24][25][26] The prevalence of abnormal Pap smear results from this study was 19.3% which is higher than that reported in previous studies from same center but is consistent with reports of studies from other regions [22,23] This study had a lower sample size than that of the previous studies in the same hospital . [24][25][26][27] In this study as in most similar studies ASCUS was the commonest and AGUS the least common subtype of the abnormal SILs. [22][23][24][25][26][27] Of the abnormal SILs reported, proportion of mild dysplasia was twice that for severe dysplasia which is consistent with similar studies. [22][23][24][25][26][27] The average CD4 count in this study was about 260 cells/mm 3 which is lower than that reported in a similar study in Southeastern Nigeria (325 cells/ mm 3) . [28] Cluster differentiation( CD4) count level has been reported in other studies to be related (inversely proportional) to severity of cervical dysplasia in HIV women.[ Table 1] [28][29][30] Higher age of HIV positive women at screening is found to be predictive of abnormal pap smear result in general and both mild and severe dysplasias speci cally which is consistent with similar studies.
[Tables 2,3,4,5][ Figures 1,2], [26][27][28][29][30] Since the mean age in this study was 43 years which is far higher than the age 21 years recommended by WHO and age 35 years previously reported as onset of ICC in the same setting, it implies that many of the women will have developed dysplasia at time of screening which can progress to invasive lesions. [31] In this study we found a signi cant negative correlation between Nadir CD4 count and severe dysplasia.
[ Table 5] This is consistent with most similar studies that show that lower CD4 counts are associated with severity of dysplasia. [22][23][24][25][26][27][28][29][30][31][32] Weakness of this study could be from the fact that these patients might not be representative of general HIV population since they are accessing care in the treatment center against all odds thus introducing bias. There is also the possibility of misinformation bias regarding some of the sociodemographic variables obtained from the women which they consider private and for fear of stigmatization. However, the strength of this study is the fact that the last study done speci cally on HIV women in our center was as far back as eleven years ago (2009). This study therefore provides current reality.

Recommendations
Early age (21 years) at initiation of screening in line with WHO guideline should be encouraged to largely prevent cervical cytological abnormalities and ICC. This should be integrated with protocol for normal care of HIV positive women which will reduce incidence of cervical ICCs in this vulnerable group. Future research with larger sample size to increase the power of the measures and including other variables like cigarette smoking, presence of sexually transmitted infections, educational and economic status should be done. Widespread education of the populace on the burden of cervical cancer and importance of screening at early age using the mass media, counseling at antenatal clinics, and the involvement of men will contribute immensely to reduction in the incidence of ICC. Decentralization of services by incorporation of cervical screening and treatment in primary health care programs will ensure adequate rural-urban coverage.

Conclusion
This study shows that prevalence of abnormal cervical cytology has remained high with increasing age at onset of screening in our setting. Thus, there is need to intensify education on early Pap smear screening including making this screening accessible, affordable and a necessary part of care among our HIV positive women.

Declarations Ethics Statement
The studies involving use of secondary data were reviewed and approved by Jos University Teaching Hospital's (JUTH) Ethical committee and AIDS prevention initiative in Nigeria (APIN). Written informed consent from the participants' legal guardian/next of kin was not required to participate in this study in accordance with the national legislation and the institutional requirements.

Consent for publication
Not applicable.

Availability of data and materials
All the relevant data for this analysis have been presented in the body of this manuscript. The original data sources and the dataset used in this analysis is available upon reasonable request to the corresponding author.

Competing interests
The authors declare that the research was conducted in the absence of any commercial or nancial relationships that could be construed as a potential con ict of interest.