Management of the Abnormal Pap Smear in HIV Positive Patients

Introduction and Background: Both human papillomavirus (HPV) and the human immunodeficiency virus (HIV) are sexually transmitted. High-risk (HR) HPV types are a causal factor in cervical cancer. Persistent HPV infection in this subset of immunocompromised women results in faster disease progression. The study determined the prevalence of HPV genotypes in cervicovaginal secretions of HIV seropositive women and the correlation with CD4 counts and cytology.Method: One hundred, non-pregnant, HIV-positive women of 18 years of age and above were enrolled in this cross-sectional study following approval by the institutional ethical committee. A written consent, questionnaire, followed by sample collection including a Papanicolaou (Pap) smear for cytology was undertaken. Cervicovaginal secretion samples were collected in the Digene® specimen transport medium (STM) (Qiagen Gaithersburg Inc., MD, USA). HPV genotyping was carried out with PCR amplification of a 65-base pair (bp) fragment in the L1 region of the HPV genome using the short PCR fragment (SPF10) primers followed by reverse hybridization by line probe assay (LPA) using the INNOLiPA HPV Genotyping Extra kit (Fujirebio, Belgium). Quantitation of HPV-16 and−18 viral loads (VLs) was done by real-time PCR. Results of Pap smear cytology were correlated with CD4 counts and HPV-16 and−18 VLs.Results: Mean age of the subjects was 34.9 years ± 7.2 years (median 33.0 years, range 24–60 years). HPV was detected in 62 of 93 (66.6%) samples. Twenty (32.25%) of these 62 samples harbored a single HPV genotype. Multiple genotypes (more than two) were detected in 38 (61.3%) samples. HPV-16 was the commonest genotype detected in 26 (27.9%) of all samples and 41.9% of HPV positive samples. Pap smear cytology was reported for 93 women included in the study. Women who had normal cytology were reported as negative for intraepithelial malignancy or lesion (NILM; n = 62; 71.36%), two women had a high-grade squamous intraepithelial lesion (HSIL), low-grade squamous intraepithelial lesion (LSIL; n = 11), atypical squamous cells of undetermined significance (ASCUS; n = 12). Those smears with inadequate material were reported as scant (n = 6). The median CD4 count was 363/cu.mm (range 39–787) in HPV-positive women compared to 423/cu.mm (range 141–996) in those HPV-negative women. Quantitation of HPV-16 and−18 VL was done in duplicate for samples positive by PCR reverse hybridization (INNOLiPA). Of these 20 samples (65%), 12 samples were positive by real-time PCR. The normalized HPV-16 VL ranged between 18 and 240,000 copies/cell. The normalized HPV-18 VL in cervical samples ranged between ~24 and 60,000 copies/cell.Conclusion: HIV-positive women may be infected with multiple genotypes other than HPV-16 and−18. This may have implications on the vaccines available currently which target few specific genotypes only. Studies are required to determine the predictive role of HR HPV genotypes, in significant copy numbers especially in HIV seropositive women. It would be clinically relevant if the HPV VLs, cervical cytology, and CD4 counts are considered into cervical cancer screening programs for triage and follow-up of these women.

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Study of Prevalence of Abnormal Pap Smear and its Associated Risk Factors in HIV Positive Women: A Cross-sectional Study

The Journal of Obstetrics and Gynecology of India ◽

10.1007/s13224-021-01533-7 ◽

2021 ◽

Author(s):

S. Prathima ◽

Sarojini ◽

B. Latha ◽

T. R. Ashakiran

Keyword(s):

Risk Factors ◽

Pap Smear ◽

Cross Sectional Study ◽

Hiv Positive ◽

Sectional Study ◽

Cross Sectional ◽

Hiv Positive Women ◽

Associated Risk Factors

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A Study of Pap Smear in HIV-Positive Females

The Journal of Obstetrics and Gynecology of India ◽

10.1007/s13224-016-0908-9 ◽

2016 ◽

Vol 66 (6) ◽

pp. 453-459 ◽

Cited By ~ 1

Author(s):

Apeksha Madan ◽

Sunita Patil ◽

Leena Nakate

Keyword(s):

Pap Smear ◽

Hiv Positive

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Awareness, perceived risk and practices related to cervical cancer and Pap smear screening: A cross-sectional study among HIV-positive women attending an urban HIV clinic in Johannesburg, South Africa

South African Medical Journal ◽

10.7196/samj.2017.v106i12.11224 ◽

2016 ◽

Vol 106 (12) ◽

pp. 1247 ◽

Cited By ~ 3

Author(s):

Idah Mokhele ◽

D Evans ◽

K Schnippel ◽

A Swarts ◽

J S Smith ◽

...

Keyword(s):

South Africa ◽

Cervical Cancer ◽

Perceived Risk ◽

Pap Smear ◽

Cross Sectional Study ◽

Hiv Positive ◽

Sectional Study ◽

Cross Sectional ◽

Hiv Positive Women ◽

Pap Smear Screening

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Pap smear outcomes in HIV-positive women ≥65 years and HIV-negative matched controls

Gynecologic Oncology ◽

10.1016/j.ygyno.2020.05.280 ◽

2020 ◽

Vol 159 ◽

pp. 183-184

Author(s):

K.L. Klein ◽

A.R. Goron ◽

G. Taylor ◽

D.M. Roque

Keyword(s):

Pap Smear ◽

Hiv Positive ◽

Hiv Positive Women ◽

Hiv Negative

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A Study of Pap Smears in HIV-Positive and HIV-Negative Women from a Tertiary Care Center in South India

Acta Cytologica ◽

10.1159/000496211 ◽

2019 ◽

Vol 63 (1) ◽

pp. 50-55

Author(s):

Kritika Gupta ◽

Cheryl Sarah Philipose ◽

Sharada Rai ◽

John Ramapuram ◽

Gagandeep Kaur ◽

...

Keyword(s):

Pap Smear ◽

Negative Control Group ◽

Negative Control ◽

Hiv Positive ◽

Control Group ◽

Pap Smears ◽

Cell Counts ◽

Cd4 Cell Counts ◽

Intraepithelial Lesion ◽

Hiv Negative

Objectives: The aim of this work was to study the spectrum of epithelial abnormalities on Pap smears of HIV-positive women categorized as per the Bethesda System of Reporting Cervical Cytology, to correlate them with CD4 lymphocyte counts, and to compare them with the spectrum of abnormalities seen in a HIV-negative control group. Study Design and Methodology: The present study was a 6-year retrospective study conducted in the Department of Pathology at Kasturba Medical College, Mangalore, which included 150 Pap smears from HIV-positive and HIV-negative women, respectively. The Pap-stained slides of the cases were retrieved and studied. The data collected were tabulated and analyzed. A statistical study was performed using SPSS software. The χ2 test was used to analyze the data and a p value < 0.05 was considered to be significant. Results: Pap smear abnormalities were twice as high in HIV-infected women (12%) as compared with HIV-negative women (6%; p = 0.006, RR = 2). Negative for intraepithelial lesion/malignancy was the most common finding (88%), which was further subdivided into inflammatory, atrophic smear, non-specific, candidiasis, and bacterial vaginitis groups. The percentage of epithelial abnormalities was 12%, including: atypical squamous cells of undetermined significance, 5.55%; atypical squamous cells, cannot exclude HSIL, 16.66%; low-grade squamous intraepithelial lesion, 5.55%; high-grade squamous intraepithelial lesion (HSIL), 61.11%, and squamous cell carcinoma, 11.11%. The highest incidence of intraepithelial lesions in HIV-positive females was in the age group of 34–49 years. CD4 cell counts fell in the range of 200–500 cells/mm3 in most of the HIV-positive patients (68.75%), but was not found to be statistically significant. Conclusion: Routine Pap smear examination is advocated in women with HIV as the prevalence of epithelial cell abnormalities was found to be 12%, which was twice as high as compared to the HIV-negative control group. Although there was no correlation of epithelial cell abnormalities with CD4 counts, a higher rate of the cases with epithelial abnormalities were observed to have CD4 cell counts of 200–500 cells/mm3.

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Factors predicting the persistence of genital human papillomavirus infections and PAP smear abnormality in HIV-positive and HIV-negative women during prospective follow-up

International Journal of STD & AIDS ◽

10.1258/095646203765371321 ◽

2003 ◽

Vol 14 (6) ◽

pp. 417-425 ◽

Cited By ~ 39

Author(s):

M Branca ◽

A R Garbuglia ◽

A Benedetto ◽

T Cappiello ◽

L Leoncini ◽

...

Keyword(s):

Multivariate Analysis ◽

Human Papillomavirus ◽

Pap Smear ◽

Clinical Course ◽

Univariate Analysis ◽

Hiv Positive ◽

Cervical Lesions ◽

Oncogenic Hpv ◽

Hiv Negative

As part of an extensive multi-institutional DIANAIDS study focused on assessing the risk factors, natural history, diagnosis and follow-up of genital human papillomavirus (HPV) infections in HIV-infected women, the present communication reports a sub-cohort of 142 women (89 HIV+ and 48 HIV-), followed-up for a mean of 14.07 (±10.84) months to analyse the factors predicting the persistence and clearance of HPV infections (polymerase chain reaction [PCR] and sequencing) and cervical Papanicolaou (PAP) smear abnormalities, using both univariate (Kaplan-Meier) and multivariate (Cox) survival analysis. The appearance of new HPV infections during the follow-up was significantly more frequent in HIV-positive than in HIV-negative women, odds ratio (OR) 8.800 (95% confidence interval [CI]: 1.199-64.611), and also the clearance rate was significantly less frequent in HIV-positive than in HIV-negative women, 69.2% vs 22.8%, respectively (OR 0.330; 95% CI: 0.163-0.670). These two groups were also markedly different with respect to the clinical course of the cervical lesions, in the frequency of progressive disease (determined by PAP smear) was higher in HIV-positive group (12/89) than in HIV-negative women (2/52) (OR 3.506; 95% CI 0.816-15.055) ( P = 0.055), in whom the disease regressed more frequently than in HIV-positive women (13.5% vs 7.9%) (OR 0.584; 95% CI 0.217-1.573). Using (1) HPV-positivity, (2) oncogenic HPV-type and (3) significant PAP smear abnormality at the end of follow-up as outcome measures, (1) was significantly ( P < 0.001) predicted by the following variables in univariate analysis: age, mode of contraception, CD4 count, and HIV-positivity. The significant predictors of (2) were age and mode of contraception. The outcome measure (3) was significantly predicted by CD4 count, PAP smear abnormality and PCR status at entry. In the multivariate analysis, the significant independent predictive factors for HPV-positivity proved to be only the HIV status ( P < 0.001), and PCR status at entry, p53 polymorphism at aa-72, oncogenic HPV type and significant PAP smear at entry remained independent predictors, with the significance level of P < 0.05. None of the significant predictors of oncogenic HPV type in univariate analysis retained their independent value in multivariate analysis. Oncogenic HPV type at entry proved to be an independent predictor of significant PAP smear ( P < 0.05). The present results indicate that HIV-infected women, even on highly active antiretroviral therapy, demonstrate a more aggressive clinical course of cervical HPV infections, and fail to eradicate the disease more frequently than HIV-negative women. This persistence of HPV-positivity, oncogenic HPV type and significant PAP smear abnormality can be predicted by the results of PAP test and HPV typing in univariate analyses, and partly retain their independent predictive value also in multivariate analysis. Clearly, in addition to regular monitoring by PAP smear, HPV testing for the oncogenic HPV types seems to provide additional prognostic information in the management of cervical lesions in HIV-infected women.

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