Prevalence, Risk Factors, and Accuracy of Cytologic Screening for Cervical Intraepithelial Neoplasia in Women with the Human Immunodeficiency Virus

doi:10.1006/gyno.1998.4938

Gynecologic Oncology

Volume 68, Issue 3, March 1998, Pages 233-239

https://doi.org/10.1006/gyno.1998.4938 Get rights and content

Abstract

Objectives.The objective was to evaluate the sensitivity and specificity of cervical cytology in women infected with the human immunodeficiency virus (HIV), risk factors for abnormal cytology in HIV-infected and uninfected women, and risk factors for histologic diagnosis of cervical intraepithelial neoplasia (CIN) in HIV-infected women.

Methods.Methods included a cross-sectional analysis of cervical cytology, colposcopic impression, and histology in 248 HIV-infected women and multivariate analyses of risk factors for abnormal cytology in 253 HIV-infected and 220 uninfected women and risk factors for CIN in 186 HIV-infected women.

Results.The sensitivity and specificity of cytology for all CIN grades were 0.60 and 0.80 and, for high-grade CIN, 0.83 and 0.74. The prevalence of abnormal cytology was 32.9% in HIV-infected and 7.6% in HIV-negative women. Independent risk factors for abnormal cytology were immunodeficiency [odds ratio (OR) 8–17,P< 0.001] and human papillomavirus (HPV) infection (OR = 5,P< 0.001). The prevalence of CIN on histology was 32% in HIV-infected women, and the only independent risk factor for CIN was oncogenic HPV type (OR = 5,P= 0.005).

Conclusion.Given the high prevalence of abnormal cytology and CIN in HIV-infected women, cytologic screening has significant limitations. Both immunodeficiency and type of HPV infection are important risk factors.

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Cited by (106)

Diagnostic accuracy of cervical cancer screening strategies for high-grade cervical intraepithelial neoplasia (CIN2+/CIN3+) among women living with HIV: A systematic review and meta-analysis
2022, eClinicalMedicine
Citation Excerpt :
The majority of studies were cross-sectional (n=29) and conducted in Sub-Saharan Africa (SSA; n=19; Table 1). Thirteen studies enrolled WLHIV attending cervical cancer screening in outpatient gynaecology clinics,24–36 whereas 21 studies recruited WLHIV attending HIV clinics.37–57 Two studies recruited WLHIV with a prior positive screen-test (HPV-positive)58,59 and two studies included a combination of women attending primary care and women referred to colposcopy because of positive HPV test and/or abnormal cytology.60,61
We systematically reviewed the diagnostic accuracy of cervical cancer screening and triage strategies in women living with HIV (WLHIV).
Cochrane Library, Embase, Global Health and Medline were searched for randomised controlled trials, prospective or cross-sectional studies published from database inception to 15 July 2022 reporting diagnostic accuracy of tests in cervical cancer screening and triage of screen-positive WLHIV. Studies were included if they reported the diagnostic accuracy of any cervical cancer screening or triage strategies for the detection of histologically-confirmed high-grade cervical intraepithelial neoplasia (CIN2+/CIN3+) among WLHIV. Summary data were extracted from published reports. Authors were contacted for missing data where applicable. Sensitivity and specificity estimates for CIN2/3+ were pooled using models for meta-analysis of diagnostic accuracy data. Study quality was assessed using the QUADAS-2 tool for the quality assessment of diagnostic accuracy studies. PROSPERO registration:CRD42020189031.
In 38 studies among 18,737 WLHIV, the majority (n=19) were conducted in sub-Saharan Africa. The pooled prevalence was 12.0% (95%CI:9.8-14.1) for CIN2+ and 6.7% (95%CI:5.0-8.4) for CIN3+. The proportion of screen-positive ranged from 3-31% (visual inspection using acetic acid[VIA]); 2-46% (high-grade squamous intraepithelial lesions, and greater [HSIL+] cytology); 20-64% (high-risk[HR]-HPV DNA). In 14 studies, sensitivity and specificity of VIA were variable limiting the reliability of pooled estimates. In 5 studies where majority had histology-confirmed CIN2+, pooled sensitivity was 56.0% (95%CI:45.4-66.1; I²=65%) for CIN2+ and 65.0% (95%CI:52.9-75.4; I²=42%) for CIN3+; specificity for <CIN2 was 73.8% (95%CI:59.8-84.2, I²=94%). Cytology was similarly variable (sensitivity of ASCUS+ for CIN2+ range: 58-100%; specificity: 9-96%). In 28 studies, sensitivity of tests targeting 14-HR-HPV types was high (91.6%, 95%CI:88.1-94.1; I²=45% for CIN2+ and 92.5%, 95%CI:88.4-95.2; I²=32%) for CIN3+); but specificity for <CIN2 was low (62.2% (95%CI:57.9-66.4;I²=92%). Restriction to 8-HR-HPV increased specificity (65.8%; Relative specificity[RSpec] vs. 14-HR-HPV=1.17; 95%CI:1.10-1.24) with no significant change in sensitivity (CIN2+:85.5%; Relative Sensitivity[RSens]=0.94, 95%CI: 0.89-1.00; CIN3+:90%; RSens=0.96, 95%CI:0.89-1.03). VIA triage of 14-HR-HPV positive women decreased sensitivity for CIN2+ compared to HPV-DNA test alone (64.4% vs. 91.6%; RSens=0.68, 95%CI:0.62-0.75).
HPV-DNA based approaches consistently showed superior sensitivity for CIN2+/CIN3+ compared to VIA or cytology. The low specificity of HPV-DNA based methods targeting up to 14-HR-HPV could be improved significantly by restricting to 8-HR-HPV with only minor losses in sensitivity, limiting requirement for triage for which optimal approaches are less clear.
World Health Organisation; National Cancer Institute; European Union's Horizon 2020 and Marie Skłodowska-Curie Actions programme.
Population risk factors for late-stage presentation of cervical cancer in sub-Saharan Africa
2018, Cancer Epidemiology
Cervical cancer is the most prevalent malignancy in sub-Saharan Africa (SSA) with many women only seeking professional help when they are experiencing symptoms, implying late-stage malignancy and higher mortality rates. This ecological study assesses population-level exposures of SSA women to the numerous risk factors for HPV infection and cervical cancer, against late-stage presentation of cervical cancer.
A literature review revealed the relevant risk factors in SSA. Open-access databases were mined for variables closely representing each risk factor. A proxy for late-stage presentation was used (ratio of incidence-to-mortality, IMR), and gathered from IARC’s GLOBOCAN 2012 database. Variables showing significant correlation to the IMR were used in stepwise multiple regression to quantify their effect on the IMR.
Countries with high cervical cancer mortality rates relative to their incidence have an IMR nearer one, suggesting a larger proportion of late-stage presentation. Western Africa had the lowest median IMR (1.463), followed by Eastern Africa (IMR = 1.595) and Central Africa (IMR = 1.675), whereas Southern Africa had the highest median IMR (1.761). Variables selected for the final model explain 65.2% of changes seen in the IMR. Significant predictors of IMR were GDP (coefficient = 2.189 × 10⁻⁶, p = 0.064), HIV infection (−1.936 × 10⁻³, p = 0.095), not using a condom (−1.347 × 10⁻³, p = 0.013), high parity (−1.744 × 10⁻², p = 0.008), and no formal education (−1.311 × 10⁻³, p < 0.001).
Using an IMR enables identification of factors predicting late-stage cervical cancer in SSA including: GDP, HIV infection, not using a condom, high parity and no formal education.
Hybrid capture as a tool for cervical lesions screening in HIV-infected women: insights from a Brazilian cohort
2018, Brazilian Journal of Infectious Diseases
Citation Excerpt :
However, even though the incidence of high-grade cervical lesions was higher in HIV-infected women, high-grade cervical lesions were uncommon, especially after regular screening initiation.10 Although some studies described higher false negative rates of cervical cytology among HIV-infected women when compared to HIV-uninfected counterparts,27,28 others, including more recent reports, have shown similar rates among HIV-infected and uninfected women.29–33 Regardless this controversy, cytology has been the method of choice for cervical cancer screening in all populations, including HIV-infected women.13
Cervical cancer remains an important burden for HIV-infected women in the era of combination antiretroviral therapy. Recommendations for cervical screening in these women diverge and may include high-risk HPV (HRHPV) testing. We aimed to evaluate the clinical usefulness of a single HRHPV testing for cervical screening of HIV-infected women.
723 HIV-infected women from a Brazilian prospective cohort were included between 1996 and 2012. Inclusion criteria were: normal cervical cytology at baseline and having a HRHPV-test at baseline. We calculated incidence rates of any squamous intraepithelial lesion (SIL) and high grade SIL+ (HSIL+) and negative predictive values (NPV) within 12 and 36 months. Hazard Ratios were obtained using Cox proportional hazards regression models.
Incidence rate for both outcomes was low (9.9 cases per 100 PY [95% CI 8.8–11.0] for any SIL and 1.3 cases per 100 PY [95% IC 0.9–1.8] for HSIL+). Women with a HRHPV positive status at baseline had 1.7-fold (95% CI 1.3–2.2) and 3.2-fold (95% CI 1.5–7.1) increased risk of presenting any SIL and HSIL+, respectively, during follow-up. Negative-HRHPV test presented high NPV for both periods and outcomes (any SIL: 92.4% [95% CI 89.7–94.6] for 12 months and 80.9% [95% CI 77.2–84.3] for 36 months; and HSIL+: 99.8% [95% CI 98.9–100.0] for 12 months and 99.0 [95% CI 97.6–99.7] for 36 months).
Incidence of any and high grade cytological abnormality was significantly higher among HIV-infected women with positive-HRHPV test. A single negative-HRHPV test helped reassure follow-up free of cytological abnormalities through three years of follow-up in HIV-infected women with negative cytology.
Cervical dysplasia in women with human immunodeficiency virus (HIV) in areas of high prevalence of infection
2010, Gynecologie Obstetrique et Fertilite
Déterminer la prévalence des lésions épidermoïdes intra épithéliales (LEI) cervicales chez les femmes VIH-positives, la comparer à celle des femmes VIH-négatives et identifier les différents types de lésions dans les deux groupes.
Étude transversale réalisée en 16 mois dans deux formations sanitaires et le service d’anatomie pathologique de Bangui. L’échantillon était constitué de 250 femmes VIH-positives appariées à 250 femmes séronégatives. Les paramètres étudiés étaient la sérologie VIH, le résultat du frottis cervical de dépistage, les taux des CD4 et les données de l’interrogatoire.
Les frottis étaient inflammatoires chez 54,4 % des VIH-négatives et 46,4 % des VIH-positives. Les lésions épidermoïdes intra épithéliales du col étaient plus fréquentes chez les femmes VIH-positives que chez les femmes VIH-négatives avec respectivement 34,8 % et 16,4 % (p < 0,0001). Les LEI de bas grades étaient plus fréquentes, quel que soit le statut sérologique des patientes. L’âge médian de survenue des LEI était plus bas chez les femmes VIH-positives quel que soit le grade de la lésion. La koïlocytose était retrouvée chez 27,2 % de femmes VIH-positives contre 9,2 % chez les séronégatives (p < 0,001).
La prévention de l’infection par le VIH et le HPV et la surveillance des lésions précancéreuses permettraient d’éviter leur évolution vers un cancer invasif.
To determine the prevalence of cervical squamous intraepithelial lesions among HIV-positive women, compared to that of HIV-negative women and identify the different types of lesions in both groups.
Cross-sectional study conducted in 16 months in two facilities and the service of pathological anatomy of Bangui. The sample consisted of 250 HIV-positive women matched to 250 HIV-negative women. The parameters studied were the HIV status, the result of cervical smear screening, the rates of CD4 and the data of the interview.
The smears were inflammatory in 54.4% of HIV-negative and 46.4% of HIV-positive. Epidermoid intraepithelial lesions of the cervix were more frequent among HIV-positive women than among HIV-negative women with respectively 34.8% and 16.4% (P < 0.0001). The low-grade lesions were more common regardless of HIV status of patients. The median age of onset of the LEI was lower among HIV-positive whatever the grade of the lesion. Koïlocytosis was found in 27.2% of HIV-positive women against 9.2% among HIV-negative (P <0.001).
The prevention of infection by HIV and HPV and the monitoring of precancerous lesions would allow to prevent their evolution towards invasive cancer.
Challenges in Cancer Prevention in HIV
2021, Indian Journal of Gynecologic Oncology
The interplay of HIV and human papillomavirus-related cancers in sub-Saharan Africa: Scoping review
2020, Systematic Reviews

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^☆: Supported by National Institute of Allergy and Infectious Diseases (AI318434, AI95014) and CDC/Conrad CSA-92-100.

^☆☆: Rosai, JSobin, L, H

²: To whom correspondence and reprint requests should be addressed at Department of Obstetrics and Gynecology, Box 24, SUNY-Health Science Center at Brooklyn, 450 Clarkson Avenue, Brooklyn, NY 11203. Fax: (718) 270-4173.

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Regular ArticlePrevalence, Risk Factors, and Accuracy of Cytologic Screening for Cervical Intraepithelial Neoplasia in Women with the Human Immunodeficiency Virus☆,☆☆

Abstract

Gynecol Oncol

Virus Res

Gynecol Oncol

Gynecol Oncol

Gynecol Oncol

Obstet Gynecol

Am J Obstet Gynecol

Cellular immunodeficiency enhances the progression of human papillomavirus-associated cervical lesions

Int J Cancer

Colposcopic evaluation of human immunodeficiency virus-seropositive women

Obstet Gynecol

Genital papillomavirus infection and cervical dysplasia—opportunistic complications of HIV infection

Int J Cancer

High frequency of latent and clinical human papillomavirus cervical infections in immunocompromised human immunodeficiency virus-infected women

Obstet Gynecol

Human immunodeficiency virus type 1 tat gene enhances human papillomavirus early gene expression

Inrtervirology

Tumors of the cervix, vagina and vulva

Atlas of Tumor Pathology

Regular Article
Prevalence, Risk Factors, and Accuracy of Cytologic Screening for Cervical Intraepithelial Neoplasia in Women with the Human Immunodeficiency Virus☆,☆☆