In 1993 The Centre for Disease Control and Prevention (CDC, USA) expanded the case definition of AIDS to include invasive cervical cancer. As seen in the above studies, HIV
infection is associated with invasive cervical cancer and HPV types 16 and 18 are still the commonest oncogenic HPV types implicated. However, most cases of invasive cervical cancer in HIV infection are associated with multiple high-risk HPV types unlike in the general population.90 Also, when invasive cervical cancer does occur in the setting of HIV infection, it tend to be at an age 10-15 years younger than HIV negative women with cervical cancer.91 In addition, HIV-positive women may present at more advanced stage, have poorer responses to standard therapy, and have higher recurrences and death rates, compared to HIV negative women of similar stage.92 These findings buttresses the need to incorporate regular cervical cancer screening into the protocol for managing women living with HIV/AIDS in regions with high HIV prevalence as these regions generally do not have an effective cervical cancer screening programs due to the problem of low resources.
2.8 SCREENING MODALITIES FOR CERVICAL CANCER
Invasive cervical cancer is essentially preventable because it develops from precursor lesions which can be detected and treated. An ideal screening test should be minimally invasive, easy to perform, acceptable to the subject, cost-effective and efficacious in the diagnosis of the disease in its early preinvasive stage when its more easily amenable and curable.22 The various screening techniques includes: Conventional Pap smear, Liquid – based cytology, Automated cervical screening techniques, Neuromedical systems, HPV testing, Polar probe, Lazer induced fluorescence, visual inspection of cervix after applying acetic acid (VIA), visual inspection of cervix after applying Lugol’s Iodine (VILI), speculoscopy, cervicography, pelvic examination, and colpsocopy22. Early detection of cervical cancer predicts good prognosis as the WHO predicts that 92% of cases can be detected and treated if a woman undergoes regular pelvic examination and Pap test.93
2.9 ANATOMICAL AND PATHOPHYSIOLOGICAL BASIS OF CERVICAL CANCER SCREENING METHODS94
The cervix is the cylindrical or conical portion of the uterus that measures 3-4cm in length and 2.5-3.5cm in diameter. The size and shape varies with age, parity and hormonal status. The microscopic anatomy of the cervix is composed of a dense fibromuscular tissue rich in vascular, lymphatic and nerve supplies with a lining of two types of epithelium. A stratified squamous epithelium covers a large area of the ectocervix while a single layer of tall columnar epithelium line the endocervix and also forms the endocervical glands. The squamous and columnar epithelium meets at the squamoucolumnar junction. The area of the cervix where the columnar epithelium has been replaced and/or is been replaced by metaplastic squamous epithelium is called the Transformation Zone and is the point where almost all cervical neoplasia occurs.
The nuclear characteristics of the epithelial cells are used for cytopathological evaluation during Pap test [cytology based screening].
The reflection of light from the underlying cervical stroma rich in blood vessels makes the normal squamous epithelium appear pink and the columnar epithelium red. 5% acetic acid coagulates proteins. In VIA, 3-5% acetic acid is applied to the cervix. In CIN and invasive cervical cancer, the epithelium contains a lot of cellular proteins from increased nuclear activity and DNA content and the application of 5% acetic acid coagulates the proteins which then obliterate the colour of the stroma resulting in acetowhitening. The amounts of cellular proteins present in the epithelium determine the degree of acetowhitening. In CIN, the acetowhitening is limited to the Transformation Zone close to the Squamoucolumnar junction, while in cancer it often involves the entire cervix. Conditions with increased nuclear proteins that may also show
acetowhitening include immature squamous metaplasia, healing and regenerating epithelium, leucoplakia [hyperkeratosis], and condyloma.
In VILI, iodine is applied to the cervix. Iodine is glycophilic which makes any glycogen containing epithelium to turn mahogany brown or brown black. Any epithelium containing little or no glycogen remains colourless against the coloured background. In CIN and cancer, there is no iodine uptake due to lack of glycogen resulting in thick mustard-yellow or saffron- coloured areas.
2.10 SCREENING GUIDELINES FOR CERVICAL CANCER
It is recommended that screening should begin 3 years after the onset of vaginal intercourse and not later than 21 years.95 Screening should be done every 1-3 years depending on age and history of abnormal results.95 It is disappointing to note that only about 5% of women in developing countries have been screened for cervical cancer despite the fact that more than 80% of cervical cancer related deaths occur in these developing countries.21
The American cancer society on March 14, 2012 published the new screening guidelines for cervical cancer.96 The guideline no longer recommends that women get a Pap test every year since it takes 10-20 years for cervical cancer to develop.51 The latest recommendations are as follows:
All women should begin cervical cancer screening at age 21 years
Women between 21-29 years should do Pap test every 3 years. HPV test needed only after an abnormal Pap test.
Women between 30-65 years should have both Pap test and HPV test every 5 years. Pap test alone can be done every 3 years.
Women greater than 65 years who have had regular screening and normal results should not be screened for cervical cancer. Those with a diagnosis of pre-cancer should continue screening.
Women who have had Total abdominal hysterectomy (TAH) with no history of cancer or pre-cancer should not be screened.
Women who have had HPV vaccine should still follow the screening recommendation for age group.
Women with high risk of cervical cancer may need to be screened more often. This includes HIV infection, organ transplant, or exposure to diethyl stilbesterol (DES).
Since the clinical course of HPV infection is more aggressive in immunocompromised patients, gynaecological examination is now a recommended part of the routine work up for women living with HIV/AIDS (CDC, USA). For routine screening, the CDC recommends a Pap smear at the initial visit after HIV is diagnosed, with a repeat after six months and then annually if the initial two were normal.
After reviewing the available literature, it is evident that no such study has been done in this region of Nigeria with a high HIV prevalence. Since HIV infection is a risk factor for the development of cervical cancer and precancerous lesions of the cervix are also commoner in women living with HIV/AIDS, the data generated from this study will add to existing literature and provide a local epidemiological evidence to both physicians and pathologists to justify the inclusion of cervical cancer screening as part of the protocol for management of women living with HIV/AIDS in this part of Nigeria.
CHAPTER THREE
MATERIALS AND METHODS
3.1 Study Area.
This study was carried out in University of Uyo Teaching Hospital, located in Uyo, the capital of Akwa Ibom State in the South-South geopolitical zone of Nigeria. The hospital is the only Teaching Hospital in the state and serves Uyo and its environs. This state presently has one of the highest prevalence of HIV infection in Nigeria.1 Apart from the four major ethnic groups in the state consisting of Ibibio, Anang, Eket, and Oron, the state is also known for its multi-cultural tribes including Ibos, Hausas, and Yorubas constituting a microcosm of the larger nation.
3.2 Study design.
This is a prospective cross-sectional comparative hospital based case-control study carried out between February, 2013 and April, 2014 to determine the prevalence of abnormal cervical epithelial cytology in HIV seropositive women in Uyo and correlation with CD4 counts and HIV viral load.
3.3 Study population and patient recruitment and selection.
A total of 466 consenting women were recruited for this study and comprises 231 HPW as case-participants and 235 HNW as control-case-participants. The cases included ever-married or sexually active adult females attending the HIV clinic and receiving HAART treatment while the control subjects included ever-married or sexually active adult females from the general population attending the Gynaecology, General Out-Patient, and Family planning clinics of University of
Uyo Teaching Hospital. In both groups of patients, the women were recruited by Doctor-Patient interaction using simple random sampling until the sample size was reached. The targeted recruitment was based on age, family and social history.
3.4 Exclusion criteria.
Exclusion criteria included Patients who refuse to give consent, patients bleeding per vaginum, and Patients below 18 years. Additional exclusion criteria for the case-participants included newly diagnosed patients who are yet to commence HAART while those excluded as controls also included Patients on oral contraceptives or immunosuppressive drugs, patients being managed for cervical cancer or other forms of gynaecological malignancies, and pregnant women. The control-participants were offered VCT for HIV and those that were reactive were also excluded as controls. Both groups of women were matched for age.
3.5 Sample size determination.
The sample size was calculated using the formula for calculating sample size for comparison groups and making adjustment for non-response and taking average prevalence (p) from other studies24,28 to be 0.5 and setting the degree of precision desired(d) at 0.1.97
N’= 2Z2Pq d2
Where N’= sample size for comparison groups
Z=standard normal deviate, set at 1.96 (95% confidence interval)
P=proportion of HIV positive women expected to have cervical dysplasia (0.5) q=1.0-0.5
d=degree of accuracy desired (set at 0.1)
N’=2x1.962x0.5x0.5 0.12 = 192.0.
3.6 Ethical consideration.
The study was approved by University of Uyo teaching hospital, Uyo institutional health ethical research committee [Appendix 1] and all consenting subjects signed a written informed consent [Appendix 2]. In line with the ethical statement of this study, individual results were communicated to the participants and appropriate counselling and referral was made were necessary. Those whose Pap test result showed a High grade lesion or worse were recalled for biopsy confirmation before referral.
3.7 Collaboration with other physicians.
This study was done in collaboration with Physicians in the HIV and Gynaecology clinics of University of Uyo Teaching Hospital [see Appendix 3 and 4 for letters of collaboration].
3.8 Data collection tool and technique.
A questionnaire was applied to elicit information on every woman’s background and relevant risk factors including socio-economic and marital status, menstrual and obstetric history and use of Oral contraceptive pills [Appendix 5].
All the women were screened for cervical cancer by conventional Papanicolaou (Pap) while observing standard precautions and protocols. I obtained training by consulting online instructional materials and interacting with the Gynaecologist.94,98 The Pap smears were collected under the supervision of the Gynaecologist.
3.9 Gynaecological examination and conventional Pap smear.
Each woman was placed in a dorsal position with her legs flexed at the hip and knee and abducted.
The labia were parted with gloved left thumb and index fingers.
A disposable bivalve cusco’s speculum lubricated with tepid water was passed gently into the vagina and fixed to visualize the cervix under bright light source. The cervix was examined and any gross abnormality noted.
Excess mucus was removed.
The hook end of an Ayre’s spatula was inserted into the external os of the cervix and swept through 360 degrees rotatory movement to scrape the squamocolumnar junction of the transformation zone.
Using the spatula, a smear was made on two pre-labelled frosted clean grease free slides in a thin layer of cells. The smeared slides were immersed promptly in 95% ethyl alcohol fixative contained in a coupling jar and transported to the histopathology laboratory of the hospital where the slides were stained with conventional Pap stain using standard protocols.
3.10 Cytopathological examination.
I reported the slides and these were reviewed by my supervising consultants.
The 2001 Bethesda System (TBS) of reporting cervical and vaginal cytology was used as the basis for cytology classification [see Appendix 6].
3.11 HIV testing, CD4 count and Viral load determination.
HIV testing, CD4 counts and viral load estimations were done in the PEPFAR laboratory.
The control subjects were offered Voluntary Counselling and Testing (VCT) for HIV by two rapid assays- Determine and Unigold. Those who tested positive were excluded as controls without further confirmation.
Blood for CD4 counts and HIV-1 RNA viral load determination for the HIV-positive patients was collected by a staff of the PEPFAR laboratory on the day of the Pap smear or within two weeks of the Pap smear while observing standard precaution and protocols.
The CD4 counts were performed by the Flow cytometry method while the viral load estimation was done using semi-automated conventional PCR method.
3.12 Data analysis.
The data and result collated were analysed using Microsoft Excel 2007 and SPSS version 17 and the result presented as tables and charts. Statistical comparison between the two groups was done using chi-square and Fischer exact with the level of significance set at P less or equal to 0.05.
The findings of this study were compared with those of previous studies.
CHAPTER FOUR
RESULTS
In this hospital based cross-sectional study, a total of 466 women were recruited and screened for cervical cancer using conventional Pap smear cytology but only 449 participants comprising 226 HPW and 223 HNW were used for statistical analysis. The results for seveenteen women comprising five HPW and twelve HNW were excluded due to inadequate Pap smear and incomplete data respectively.
SOCIO-DEMOGRAPHIC CHARACTERISTICS OF THE STUDY POPULATION [TABLES 1 AND 2]
The study participants were aged between 18-60 years with a mean age of 35.24±9.26 years and 35.63±8.44 years in the control- and case- participants respectively. Majority of the study participants were aged between 25-38 years. More than 80% of the study participants were below 45 years of age while only about 16% were aged 46 years and above. More than half of the HNW were married (64.1%) and had a secondary or tertiary level of education (75.6%). Only about one-third of the HPW were married (36.7%) but most of them also had a secondary or tertiary level of education (76.1%).
Most of the women in this study attained menarche at or below 14 years (72.6% of the controls and 67.3% of the cases) and also had their sexual debut at or below 18 years (55.2% of the controls and 68.1% of the cases) but most of the HPW (57.1%) have four and above lifetime number of sexual partners unlike the HNW (39.2%).
The range of parity of the women in the control group was 0-9 with a mean of 2.28± 2.3 while those of the HIV-positive group were 0-11 and 2.0±2.25 respectively. This shows that majority of the participants have a parity between 0 and 2 (57.8% of controls and 69.5% of cases). Only about one-tenth of the participants in both groups had ever used combined oral contraceptive pills while about one-third of them occasionally take alcohol. Most of the study participants are non-smokers (99.6% of HNW and 99.1% of HPW).
There was poor awareness about cervical cancer and Pap smear in the study population as is the utilization on Pap smear. In the control group of women, about 40% are aware of cervical cancer but only 9.0% of them know about Pap smear screening test. Despite the knowledge, only 8 of the women (3.6%) have ever done a Pap smear. The finding is even worse in the HIV group as only 11.5 % of them know about cervical cancer, 3.1% of them know about Pap smear and less than 1% of them have ever done a Pap smear.
OUTCOME OF CERVICAL CANCER SCREENING
1. The distribution of Pap smear result [frequency] and the Prevalence of abnormal cervical epithelial cytology according to HIV status [Table 3, Figures 1 and 2].
The result of the conventional Pap smear test in this study using the 2001 Bethesda classification shows that out of the 231 HPW, 202 (89.3%) were negative for Squamous Intraepithelial Lesions (NILM) while the rest were sub-classified as ASCUS (6 cases, 2.7%), LGSIL (13cases, 5.6 %), HGSIL (5 cases, 2.2%). Five of the HPW (2.2%) had an inadequate smear due to scant cellularity and excessive mucus obscuring the squamous epithelial cells while 22 (10.9%) of the HPW with NILM had inflammatory smear (This represents 9.7% of the total HPW). There was
no case of cervical cancer in the case-participants. Among the HNW, 212 participants (95.1%) were negative for Squamous Intraepithelial Lesion/Malignancy (NILM) while the rest were classified as ASCUS (4 cases, 1.8%), LGSIL (3 cases, 1.35%), HGSIL (3 cases, 1.35%), and Squamous cell carcinoma (1 case, 0.4%). Twelve (5.7%) of the HNW with a negative report had inflammatory smear (This represents 5.4% of the total HNW). This result makes the prevalence of cervical epithelial cell abnormality in this study to be 4.9% in the control-participants and 10.7% in the case-participants and shows that there is a significant relationship between HIV status and abnormal Pap test result (p <0.05), [see table 3].
2. Age distribution of Pap smear result and age specific prevalence rate [Tables 4 and 5].
The age distribution of the Pap smear results in this study shows that the age groups with the worst abnormal cervical epithelial cytology according to HIV status were age groups 25-31 and 39 – 45 years in the cases and 32 – 38 years in the control-participants [see table 4]. The age specific prevalence rate was highest among women that are 46 years and above in both the control- and case- participants (14.7% and 16.7% respectively) [see table 5].
3. Relationship between Duration of treatment, CD4 count and Pap test result in HPW [Table 6].
Table 6 summarizes the relationship between the duration on HAART treatment (DOT), mean CD4 count and results of Pap test in the case-participants. The mean CD4 count in this study was 311.08±299.1cells/mm3 (range 6-1779) while the mean duration of treatment was 39.40±38.7 months (range 1-140). The result show that the longer the duration on HAART treatment, the greater the level of mean CD4 count showing that there is an improvement in CD4 count with
HAART treatment. Also, women with the longest duration of treatment also have the highest percentage of normal and abnormal cervical epithelial cytology. This suggest that improved CD4 count in HPW on HAART may prevent establishment of new HPV associated cervical lesion but does not lead to the regression of established cervical lesions.
4. Relationship between Mean CD4 count, HIV-1 Viral load and Pap test result in HPW [table 7]
Table 7 summarizes the relationship between CD4 count and Pap smear results of the 65 women that had their HIV-1 viral load estimated. The mean HIV viral load in this study was 354,449.51±1,257,979.9 microliter (Range <400 - 9,623,070). The result showed that women with viral load of less than 400 also have the highest mean CD4 counts.
5. Distribution of Pap result according to CD4 count category in HPW [Table 8].
Table 8 below summarises the distribution of Pap test result according to CD4 category in HPW.
The result shows that there is no statistically significant relationship between the CD4 cell category and the type of Pap smear result seen in HPW (p value >0.05).
6. Correlation between DOT, CD4 count and HIV-1 viral load [Table 9].
In this study, there was poor correlation between the duration on HAART, mean CD4 cell count and mean HIV-1 viral load in the HPW. While the CD4 cell count was improving with HAART, some women still have a high viral load despite the initiation of HAART. On bivariate
correlation, the Viral Load does not show a significant negative correlation with the CD4 count (r = -0.034; p > 0.05).
Table 1: Socio-demographic and Clinical characteristics
Characteristics
HIV negative (n=223)
HIV positive (n=226)
Age Number (%) Number (%)
18-24 15 (6.7) 14 (6.2)
25-31 61 (27.4) 61 (27.0)
32-38 64 (28.7) 62 (27.4)
39-45 49(22.0) 53 (23.5)
≥ 46 34 (15.2) 36 (15.9)
Age at Menarche
≤ 14 162 (72.6) 152 (67.3)
≥ 15 61(27.4) 74 (32.7)
Age at first intercourse
≤ 18 123(55.2) 154 (68.1)
≥ 19 100 (44.8) 72 (31.9)
Life time No. Of sexual partners
1₋3 136 (61.0) 97 (42.9)
≥ 4 87 (39.0) 129 (57.1)
Parity
0-2 129 (57.8) 157 (69.5)
3₋5 73 (32.7) 51 (22.6)
≥ 6 21 (9.4) 18( 8.0)
Oral contraceptive use
yes 29 (13.0) 24 (10.6)
No 194 (87.0) 202 (89.4)
Alcohol use
Yes 96 (43.0) 74 (32.7)
No 127 (57.0) 152 (67.3)
Smoking
Yes 1 (0.4) 2 (0.9)
No 222 (99.6) 224 (99.1)
Table 2: Important socio-demographic factors of the HPW.
Characteristics
Total
No. Mean ±SD
Age 226 35.63 ± 8.44
CD4 226 311.08 ± 299.1
Viral load 65 354449.51 ± 1257979.9
DOT 226 1.31 ± 0.9
Key: DOT is Duration on HAART treatment
Table 3: Distribution of Pap result according to HIV status.
HIV STATUS
Pap Test Result HNW No. (%) HPW No. (%) chi-square p value
NILM 212 (95.1) 202 (89.3) 12.12 0.03
ASC-US 4 (1.8) 6 (2.7)
LGSIL 3 (1.3) 13 (5.8)
HGSIL 3 (1.3) 5 (2.2)
SQCC 1 (0.4) 0 (0)
TOTAL 223 (100) 226 (100)
key:NILM (negative for squamous intraepithelial lesion/malignancy), ASC-US(atypical squamous cells of uncertain significance), LGSIL (low grade suamous intraepithelial lesion), HGSIL (high grade squamous intraepithelial lesion), SQCC (squamous cell carcinoma). HPW (hiv positive women), HNW (hiv negative women). Five smears of HPW were inadequate.
Table 4: Age distribution of Pap test result according to HIV status.
PAP Smear Result in Number and (%)
HIV Status AGE Group NILM-I NILM ASCUS LGSIL HGSIL SQCC
HNW 18 - 24 0 (0) 15 (7.5) 0 (0) 0 (0) 0 (0) 0 (0)
25 - 31 3 (25.0) 55 (27.5) 0 (0) 2 (66.7) 1 (33.3) 0(0)
32 - 38 3 (25.0) 59 (29.5) 1 (25.0) 0 (0) 0 (0) 1 (100)
39 - 45 5 (41.7) 43 (21.5) 0 (0) 0 (0) 1 (33.3) 0 (0)
≥46 1 (8.3) 28 (14.0) 3 (75.0) 1 (33.3) 1 (33.3) 0 (0)
Total 12 (100) 200 (100) 4 (100) 3 (100) 3(100) 1 (100)
HPW 18 - 24 1 (4.5) 11 (6.1) 2 (33.3) 0 (0) 0 (0) 0 (0)
25 - 31 4 (18.2) 52 (28.9) 1 (16.7) 2 (15.4) 2 (40.0) 0 (0) 32 -38 2 (9.1) 51 (28.3) 1 (16.7) 6 (46.2) 1 (20.0) 0 (0)
39 - 45 8 (36.4) 39 (21.7) 0 (0) 1 (7.7) 2 (40.0) 0 (0)
≥46 7 (31.8) 27 (15.0) 2 (33.3) 4 (30.8) 0 (0) 0 (0)
Total 22 (100.0) 186 (100.) 6(100) 13 (100.0) 5 (100.0) 0 (0)
key: HNW [HIV negative women], HPW [HIV positive women], NILM [negative for squamous intraepithelial lesion/malignancy], NILM-I [nilm with inflammatory smear], LGSIL [low grade squamous intraepithelial lesion], HGSIL [high grade suamous intraepithelial lesion], SQCC [invasive suamous cell cervical cancer].
Figure 1: Pie chart showing the distribution of Pap results in control-participants
5.4%
89.7%
1.8% 1.3% 1.3% 0.4%
HIV Negative Women
inflam NSIL Ascus LSIL HSIL CxCa
Figure 2: Pie chart showing the distribution of Pap results in the case-participants.
9.7%
79.6%
2.7%
5.8%
2.2%
HIV Positive Women
inflam NSIL Ascus LSIL HSIL
Table 5: Age specific prevalence rate according to HIV status.
Age
Group No. Screened No. Positive Age Specific Prevalence (%)
HNW 18-24 15 0 0
25-31 61 3 4.9
32-38 64 2 3.1
39-45 49 1 2
≥46 34 5 14.7
Total 223 11
HPW 18-24 14 2 14.3
25-31 61 5 8.2
32-38 62 8 12.9
39-45 53 3 5.7
≥46 36 6 16.7
Total 226 24
Table 6: Relationship between Duration on HAART treatment, Mean CD4 cell count and Pap test result in the case-participants [HPW].
DOT MEAN CD4 NILM-I NILM ASCUS LGSIL HGSIL TOTAL (MONTHS) ± SD NO. (%) NO. (%) N0. (%) NO.(%) NO.(%) NO.(%) 1−6 242.67±217.10 9 (4.0) 60(26.5) 3(1.35) 5(2.2) 1(0.4) 78(34.5) 7−12 268.88±193.18 3(1.3) 11(4.9) 0(0) 2(0.9) 0(0) 16(7.1) 13-18 236.44±219.68 1(0.4) 7(3.1) 0(0) 1(0.5) 0(0) 9(4.0)
≥19 358.25±349.94 9(4.0) 102(45.1) 3(1.35) 5(2.2) 4(1.8) 123(54.4) TOTAL 307.35±298.68 22(9.7) 180(79.6) 6(2.7) 13(5.8) 5(2.2) 226(100) key: DOT (duration on HAART treatment), NILM (negative for squamous intraepithelial lesion/malignancy), NILM-I (nilm with inflammatory smear), ASC-US (atypical squamous cells of uncertain significance), LGSIL (low grade suamous intraepithelial lesion), HGSIL (high grade squamous intraepithelial lesion). Five smears of HPW were inadequate.
Table7: The relationship between Mean CD4 count, HIV Viral load and Pap test result in the case-participants [HPW].
VL
HPW MEAN CD4 NILM-I NILM ASCUS LGSIL HGSIL TOTAL
± SD NO. (%) NO. (%) NO. (%) NO. (%) NO. (%) NO. (%)
<400 27 301.89±260.1 2 (3.1) 21 (32.3) 0 (0) 2 (3.1) 2 (3.1) 27 (41.6)
401-10,000 7 138.29±90.1 0 (0) 7 (10.8) 0 (0) 0 (0) 0 (0) 7 (10.8)
>10,000 31 78.71±74.6 6 (9.2) 23 (35.4) 1 (1.5) 1 (1.5) 0 (0) 31 (47.6) TOTAL 65 177.83±205.6 8 (12.3 ) 51 (78.5 ) 1 ( 1.5) 3 ( 4.6) 2 (3.1) 65 100)
key: VL (HIV-1 RNA viral load), NILM (negative for squamous intraepithelial lesion/malignancy), NILM-I (NILM with inflammatory smear), ASC-US (atypical squamous cells of uncertain significance), LGSIL (low grade suamous intraepithelial lesion), HGSIL (high grade squamous intraepithelial lesion).
Table 8: The relationship between CD4 count category and Pap test result in HPW.
PAP TEST
<200
NO.(%) 200- 500 NO. (%) >500 NO. (%) Total NO.(%)
Chi-square
P-value
NILM-I 13 (12.7) 7 (9.7) 2 (3.8) 22 (9.7) 10.77 0.08
NILM 80 (78.4) 55 (76.4) 45 (86.5) 180(79.6)
ASCUS 1 (1.0) 4 (5.6) 1 (1.9) 6 (2.7)
LGSIL 5 (5.0) 5 (6.9) 3 (5.8) 13 (5.8)
HGSIL 3 (2.9) 1 (1.4) 1 (1.9) 5 (2.2)
Total 102 (100) 72 (100) 52 (100) 226 (100)
Table 9: Relationship between DOT, Mean CD4 and Mean VL
DOT (MONTHS) MEAN CD4 ±SD MEAN VL ±SD NO. OF HPW WITH VL
1−6 245.47±217.1 1126.71±1922.7 7
7−12 268.88±193.18 2,412,450.75±4,807,094.57 4
13-18 246.40±209.49 208,701.00±182,679.55 3
≥19 365.10±350.87 250,106.37±518,754.10 51
TOTAL 65
KEY: DOT [DURATION ON HAART], VL [VIRAL LOAD]
MORPHOLOGIC RESULTS
1. NILM [Negative for Intraepithelial Lesion/Malignancy].
Figure 3: Photomicrograph of the Pap test result from a normal cervix in a 32 year old woman [NIML]. Spread of superficial, Intermediate and metaplastic cells with fine chromatin pattern and regular nuclear contours and normal nucleocytoplasmic ratio. The background is clean. [Pap stain x 400]
2. ASC-US [Atypical Squamous Cells of Undetermined Significance].
Figure 4: Photomicrogragh of the Pap result showing ASC-US in a 60 year old woman.
The cells show nuclear enlargement with minimal hyperchromasia. The chromatin pattern is finely granular and the nuclear margins are fairly regular. The background show inflammatory cells. [Pap stain x 40].
3. LGSIL [Low Grade Squamous Intraepithelial Lesions].
Figure 5: Photomiicrograph of the Pap result showing LGSIL in a 40 year old woman:
Large polygonal cells show nuclear enlargement with mild nuclear hyperchromasia and moderate variation in nuclear size. The chromatin pattern is fine and there is subtle
irregularity of the nuclear contours in some cells with distinct cytoplasmic borders. Some of the cells show perinuclear clearing associated with HPV infection. [Pap stain x 400].