Cancer Biomarkers to Improve Performance of Xpert HPV for Cervical Cancer Screening

PURPOSE We evaluated whether cancer biomarkers improve the performance of Xpert human papillomavirus (HPV) testing as screening for cervical intraepithelial neoplasia grade 2 or greater (CIN2+). METHODS In a clinical study in Cape Town, South Africa, 418 HIV-negative and 426 HIV-positive women, age 30 to 65 years, were recruited. All women had cervical samples collected and underwent colposcopy and histologic sampling with consensus pathology review. Cervical samples were tested onsite using Xpert HPV, which detects 14 high-risk HPV types in 5 channels: HPV 16; HPV 18 and -45; HPV 31, -33, -35, -52, and -58; HPV 51 and -59; and HPV 39, -56, -66, and -68. Cycle threshold (Ct) values are outputted for each channel. Samples were also tested using real-time polymerase chain reaction to detect mRNA for CDKN2A, TOP2A, and MKi-67. Results were reported as ΔCt values relative to internal controls. Logistic regression and receiver operating characteristic curves were used to evaluate associations between Ct values for HPV and biomarkers with CIN2+. RESULTS Ct values from channels detecting HPV 16, -18, -45, -33, -35, -52, and -58 were informative to predict CIN2+. Area under the curve was 0.906 in HIV-negative and 0.870 in HIV-positive women. When sensitivity was set at 80%, specificity was 94.0% in HIV-negative and 82.7% in HIV-positive women. ΔCt values for detection of mRNA for CDKN2A and MKi-67 added significant improvement to the prediction of CIN2+ when included with the Ct values from the 3 informative Xpert channels. Including both HPV and biomarker parameters, area under the curve was 0.944 in HIV-negative and 0.913 in HIV-positive women. When sensitivity was set at 80%, specificity was 97.3% in HIV-negative and 89.6% in HIV-positive women. CONCLUSION Improvements in specificity of a round of screening using Xpert HPV can be achieved with the addition of cancer biomarkers.

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Residual Disease and HPV Persistence after Cryotherapy for Cervical Intraepithelial Neoplasia Grade 2/3 in HIV-Positive Women in Kenya

PLoS ONE ◽

10.1371/journal.pone.0111037 ◽

2014 ◽

Vol 9 (10) ◽

pp. e111037 ◽

Cited By ~ 13

Author(s):

Hugo De Vuyst ◽

Nelly R. Mugo ◽

Silvia Franceschi ◽

Kevin McKenzie ◽

Vanessa Tenet ◽

...

Keyword(s):

Cervical Intraepithelial Neoplasia ◽

Residual Disease ◽

Intraepithelial Neoplasia ◽

Hiv Positive ◽

Cervical Intraepithelial Neoplasia Grade ◽

Hiv Positive Women

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Human papillomavirus type-specific risk of cervical cancer in a population with high human immunodeficiency virus prevalence: case–control study

Journal of General Virology ◽

10.1099/vir.0.034298-0 ◽

2011 ◽

Vol 92 (12) ◽

pp. 2784-2791 ◽

Cited By ~ 27

Author(s):

Pontus Naucler ◽

Flora Mabota da Costa ◽

Joao Leopoldo da Costa ◽

Otto Ljungberg ◽

Antonio Bugalho ◽

...

Keyword(s):

Cervical Cancer ◽

Human Immunodeficiency Virus ◽

Human Papillomavirus ◽

Effect Modification ◽

Hiv Positive ◽

Hpv 16 ◽

Cervical Cancer Risk ◽

Hiv Positive Women ◽

Immunodeficiency Virus ◽

Hiv Negative

There are limited data on human papillomavirus (HPV) type-specific cervical cancer risk among human immunodeficiency virus (HIV)-positive women. Previous studies have suggested that HPV 16 would be relatively less important as a causative agent among HIV-positive compared with HIV-negative women. This study investigates HPV type-specific cervical cancer risk in a population in which HIV is endemic. At the Central Hospital, Maputo, Mozambique, 221 cervical cancer cases and 203 hospital-based controls were consecutively enrolled. HPV typing from cervical samples, HIV testing and recording of socio-demographic factors were performed. Logistic regression modelling was used to assess HPV type-specific risk and effect modification between HIV and HPV infection. Infection with HPV 16, 18 and ‘high-risk non-HPV 16/18 types’ (HPV 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59) was associated with cervical cancer in both crude and adjusted analyses. HPV 16 and 18 were the most common types detected in cancer biopsies among both HIV-negative and HIV-positive women. There was no significant evidence of effect modification between any HPV type and HIV infection, and there were no significant differences in the HPV type-specific prevalence when cervical cancers among HIV-positive and HIV-negative women were compared. Within the limitations of the study, the relative importance of different HPV types in cervical carcinogenesis appears not to be modified greatly by HIV infection, suggesting that HPV vaccines might not need to be type-specifically modified to be suitable for populations where HIV is endemic.

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Features of papillomavirus infection in HIV-infected women

Epidemiology and Infectious Diseases (Russian Journal) ◽

10.17816/eid40631 ◽

2012 ◽

Vol 17 (4) ◽

pp. 9-11

Author(s):

E. S Sverdlova ◽

T. V Dianova

Keyword(s):

Cervical Cancer ◽

Significant Contribution ◽

Intraepithelial Neoplasia ◽

Hpv Infection ◽

Hiv Positive ◽

Papillomavirus Infection ◽

Hiv Positive Women ◽

Selection Of Patients ◽

Selection Of ◽

Hiv Negative

As participation of immune system in the protection of human papillomavirus (HPV) has been proven, the incidence of HPV infection leading to cervical intraepithelial neoplasia (CIN) among HIV-positive women is 4 times higher than in HIV-negative cases. In the presence of HIV HPV implements oncoprogram during 6-12 months. Сytokine imbalance makes a significant contribution to the progression of HIV in combination with HPV. The criteria of selection of patients with HIV for therapy cytokines in CIN 2-3 (Roncoleukin used in the author's scheme). Using Ronkoleukin in combination with HAART in HIV-positive women can delay the progression of CIN 2-3 in cervical cancer. The criteria of selection of HIV female patients for the therapy with cytokines at the 2-3 stage of CIN ( Roncoleukin was used in the author's scheme) have been detected. Application Roncoleukin in combination with HAART in HIV-positive women can delay the progression of cervical cancer at the CIN 2-3 stage.

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Abstract 69: To Triage or Not? Positive Predictive Value of Visual Inspection with Acetic Acid for Diagnosis of Cervical Intraepithelial Neoplasia Grade 2 or Worse (CIN2+) among HIV-Positive Women in a Low-Resource Setting

10.1158/1538-7755.asgcr21-69 ◽

2021 ◽

Author(s):

Chemtai Mungo ◽

Cyrillus Ogollah ◽

Jennifer Ambaka ◽

Magdalene Randa ◽

Jackton Omoto ◽

...

Keyword(s):

Acetic Acid ◽

Positive Predictive Value ◽

Predictive Value ◽

Visual Inspection ◽

Intraepithelial Neoplasia ◽

Hiv Positive ◽

Cervical Intraepithelial Neoplasia Grade ◽

Hiv Positive Women ◽

Resource Setting ◽

Low Resource Setting

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Epidemiology of HPV in HIV-Positive and HIV-Negative Fertile Women in Cameroon, West Africa

Infectious Diseases in Obstetrics and Gynecology ◽

10.1155/2009/810596 ◽

2009 ◽

Vol 2009 ◽

pp. 1-6 ◽

Cited By ~ 9

Author(s):

Andrew J. Desruisseau ◽

Delf Schmidt-Grimminger ◽

Edith Welty

Keyword(s):

High Risk ◽

Quadrivalent Vaccine ◽

Hiv Positive ◽

Hiv Status ◽

Cross Sectional ◽

Hiv Positive Women ◽

Current Vaccine ◽

High Risk Hpv ◽

Oncogenic Hpv ◽

Hiv Negative

Background. HPV types vary by country and HIV status. There are no data on the prevalent HPV genotypes from Cameroon.Methods. We conducted a cross-sectional, observational study on 65 Cameroonian women. Samples were sent for HPV genotyping and Thin Prep analyses.Results. 41 out of 61 samples tested (67.2%) had HPV subtypes detected. The most common high risk types encountered were: 45 (24.6%) and 58 (21.5%). HIV-positive women were more likely to test positive for any HPV (P=.014), have more than one HPV subtype (P=.003), and to test positive for the high risk subtypes (P=.007). Of those with high risk HPV, HIV-positive women were more likely to have Thin Prep abnormalities than HIV-negative women (P=.013).Conclusions. Oncogenic HPV subtypes 45 and 58 were more prevalent than those subtypes carried in the quadrivalent vaccine. Further studies are needed to assess whether the current vaccine will be effective in this region.

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PE-1 Vaginal microbiota composition and persistent high-risk HPV infection in HIV negative and HIV positive women

JAIDS Journal of Acquired Immune Deficiency Syndromes ◽

10.1097/01.qai.0000558018.63419.fa ◽

2019 ◽

Vol 81 ◽

pp. 65

Author(s):

Eileen Dareng ◽

Sally Adebamowo ◽

Bing Ma ◽

Jacques Ravel ◽

Paul Pharoah ◽

...

Keyword(s):

High Risk ◽

Hpv Infection ◽

Vaginal Microbiota ◽

Hiv Positive ◽

Microbiota Composition ◽

Hiv Positive Women ◽

High Risk Hpv ◽

Hiv Negative

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Serological Detection of Human Papillomavirus Type 16 Infection in Human Immunodeficiency Virus (HIV)-Positive and High-Risk HIV-Negative Women

Clinical and Vaccine Immunology ◽

10.1128/cvi.13.4.511-519.2006 ◽

2006 ◽

Vol 13 (4) ◽

pp. 511-519 ◽

Cited By ~ 15

Author(s):

Michael J. Silverberg ◽

Michael F. Schneider ◽

Barbara Silver ◽

Kathryn M. Anastos ◽

Robert D. Burk ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Human Papillomavirus ◽

Viral Replication ◽

Smoking History ◽

Hiv Positive ◽

Hpv 16 ◽

Serial Measurement ◽

Hiv Positive Women ◽

Immunodeficiency Virus ◽

Hiv Negative

ABSTRACT Serial measurement of antibodies has not been used to provide evidence of active viral replication of human papillomavirus (HPV). Serum specimens from sequential study visits contributed by 642 human immunodeficiency virus (HIV)-positive and 116 HIV-negative participants enrolled in the Women's Interagency HIV Study were used to detect significant rises in HPV type 16 (HPV-16) antibody levels. Factors associated with a significant rise were identified using multivariable logistic regression models with generalized estimating equations. Among HIV-positive women, 8.3% of 1,997 pairs showed antibody rises, compared to 6.1% of 361 pairs among HIV-negative women (P = 0.191). For HIV-positive women, rises were associated with current (odds ratio [OR], 23.4; P < 0.001) or past (OR, 8.9; P < 0.001) HPV-16 infection relative to never being HPV-16 infected and with CD4+ cell counts (OR per 100-cell increase, 0.8; P < 0.001) but not with sexual behavior. For HIV-negative women, rises were associated with past (OR, 10.9; P = 0.033) HPV-16 infection relative to no HPV-16, current cigarette smoking (OR, 5.0; P = 0.029) relative to no smoking history, and having 6 to 10 lifetime sexual partners compared to 0 to 5 partners (OR, 9.9; P = 0.036). Serial measurement of HPV-16 serum antibodies is a useful tool for identifying active HPV-16 viral replication. Rises among HIV-positive women may more often result from reactivation of a latent HPV infection in the context of HIV-induced immunosuppression, while rises among HIV-negative women may more often result from reinfection with HPV.

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Recurrence of cervical intraepithelial neoplasia grades 2 or 3 in HIV-infected women treated by large loop excision of the transformation zone (LLETZ)

Sao Paulo Medical Journal ◽

10.1590/s1516-31802008000100004 ◽

2008 ◽

Vol 126 (1) ◽

pp. 17-22 ◽

Cited By ~ 6

Author(s):

Fábio Russomano ◽

Aldo Reis ◽

Maria José Camargo ◽

Beatriz Grinsztejn ◽

Maria Aparecida Tristão

Keyword(s):

Cervical Intraepithelial Neoplasia ◽

Highly Active Antiretroviral Therapy ◽

Intraepithelial Neoplasia ◽

Hiv Positive ◽

Hiv Patients ◽

Transformation Zone ◽

Large Loop ◽

Hiv Positive Women ◽

Hiv Negative

CONTEXT AND OBJECTIVE: Women infected by HIV are more likely to have cervical cancer and its precursors. Treatment of the precursor lesions can prevent this neoplasia. The aim of this study was to assess the likelihood of recurrent cervical intraepithelial neoplasia grades 2 or 3 (CIN 2-3) in HIV-infected women, compared with HIV-negative women, all treated by large loop excision of the transformation zone (LLETZ). DESIGN AND SETTING: A cohort study in Instituto Fernandes Figueira, Fundação Oswaldo Cruz (IFF-Fiocruz), Rio de Janeiro. METHOD: 55 HIV-positive and 212 HIV-negative women were followed up after LLETZ for CIN 2-3 (range: 6-133 months). RESULTS: The incidence of recurrent CIN 2-3 was 30.06/10,000 woman-months in the HIV-positive group and 4.88/10,000 woman-months in the HIV-negative group (relative risk, RR = 6.16; 95% confidence interval, CI: 2.07-18.34). The likelihood of recurrence reached 26% at the 62nd month of follow-up among the HIV-positive women, and remained stable at almost 0.6% at the 93rd month of follow-up among the HIV-negative women. We were unable to demonstrate other prognostic factors relating to CIN recurrence, but the use of highly active antiretroviral therapy (HAART) may decrease the risk of this occurrence among HIV patients. CONCLUSION: After LLETZ there is a higher risk of recurrence of CIN 2-3 among HIV-positive women than among HIV-negative women. This higher risk was not influenced by margin status or grade of cervical disease treated. The use of HAART may decrease the risk of this occurrence in HIV patients.

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Incidence of Cytological Abnormalities in Pap's Smear in HIV Positive Women

Journal of Medical Research and Innovation ◽

10.15419/jmri.136 ◽

2018 ◽

Vol 2 (S1) ◽

pp. e000136

Author(s):

Suhana Jotva ◽

Hemani Desai ◽

Hansa Goswami

Keyword(s):

Trichomonas Vaginalis ◽

Clinical History ◽

Hiv Positive ◽

Squamous Intraepithelial Lesions ◽

Squamous Cells ◽

Medical College ◽

Hiv Positive Women ◽

Cytological Abnormalities ◽

Intraepithelial Lesions ◽

Hiv Negative

Aims and Objectives: The aim of present study is to estimate the frequency of abnormal PAP’s smears and mainly to detect precancerous and cancerous lesions as well as inflammatory lesions in HIV infected women. Methodology: Our study was a retrospective study of total 130 cases and PAP’s smears were examined in cytology section in Department of Pathology, BJ Medical College, Ahmedabad from 1st March 2017 to 31st August 2017. Both HIV positive and HIV negative patients were included in the study. 80 patients were HIV negative and 50 patients were HIV positive. The clinical history and relevant parameters were noted. All the smears were processed by a conventional method using Papanicolaou stain. Results: Out of 130 cases, 118 cases were reported negative for intraepithelial lesions or malignancy (NILM). Five cases were positive for squamous intraepithelial lesions (SIL) out of which four were HIV positive. Seven cases were of atypical squamous cells of undetermined significance (ASCUS) out of which 5 were HIV positive. Three cases were showing bacterial vaginosis. 1 case was showing Trichomonas Vaginalis. 19 cases were showing changes of non-specific inflammation. 6 cases were showing atrophic changes. Conclusion: HIV infected women are at more risk to develop cervical cytological abnormalities. The study revealed a maximum number of non-specific inflammatory smears followed by smears showing atrophic changes. Smears suspicious for malignancy (ASCUS) and smears showing squamous intraepithelial lesions (SIL) were more common in HIV positive patients. Thus regular PAP’s smears screening as recommended by National AIDS Control Organization (NACO) will help in early detection of cervical abnormalities in HIV positive women.

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