Prevalence of Human Papillomavirus (HPV) Genotypes in Cervicovaginal Secretions of Human Immunodeficiency Virus (HIV) Positive Indian Women and Correlation With Clinico-Virological Parameters

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.

Download Full-text

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.

Download Full-text

Performance of OncoE6TMCervical Test in detecting cervical precancer lesions in HIV-positive women attending an HIV clinic in Bujumbura, Burundi: a cross-sectional study

BMJ Open ◽

10.1136/bmjopen-2019-029088 ◽

2019 ◽

Vol 9 (9) ◽

pp. e029088

Author(s):

Zacharie Ndizeye ◽

Sonia Menon ◽

Jean-Pierre Van Geertruyden ◽

Catherine Sauvaget ◽

Y Jacquemyn ◽

...

Keyword(s):

Low Income ◽

Cross Sectional Study ◽

Hiv Positive ◽

Low Grade ◽

Sectional Study ◽

Squamous Intraepithelial Lesion ◽

Cross Sectional ◽

Predictive Values ◽

Hiv Positive Women ◽

Intraepithelial Lesion

ObjectiveNew rapid and low-cost molecular tests for cervical cancer screening, such as the OncoE6 Cervical Test, are emerging and could be alternatives for low-income and middle-income countries. To this end, we evaluated the clinical performance of the OncoE6 Cervical Test in detecting cervical intraepithelial neoplasia (CIN) among HIV-infected women in Bujumbura, Burundi.MethodsFrom June to December 2017, a cross-sectional study was conducted in 680 HIV-positive women at the University Hospital. Women aged 25–65 years who declared having had vaginal intercourse were consecutively recruited, and cervical specimens for OncoE6, liquid-based cytology and human papillomavirus (HPV) genotyping were obtained and visual inspection with acetic acid performed. Thereafter, participants underwent a colposcopic examination. The sensitivity, specificity, and positive and negative predictive values of the different tests were calculated with reference to ‘colposcopic-histological’ diagnoses, and areas under the receiver operating curves of OncoE6 and cytology tests were compared.ResultsThe prevalence of CIN was 4.9%, and OncoE6 positivity was 3.1%. OncoE6 sensitivity varied from poor to low with increasing disease severity (42.1%, 95% CI 19.9% to 64.3% at CIN2+ threshold; and 58.3%, 95% CI 30.4% to 86.2% at CIN3+ threshold). OncoE6 had the highest specificity compared with all other tests used together. The performance of the OncoE6 test was significantly lower compared with cytology at atypical squamous cell of undetermined significance (ASCUS+) cut-off (AUC=0.68 vs 0.85, p=0.03) and low-grade squamous intraepithelial lesion (LSIL+) cut-off (AUC=0.68 vs 0.83, p=0.04) for CIN2+ diagnoses. However, the performance of the OncoE6 test was similar to that of cytology at high-grade squamous intraepithelial lesion (HSIL+) cut-off (AUC=0.68 vs 0.76; p=0.30) for CIN2+ diagnoses and was also similar to that of cytology at all cut-offs (ASCUS+, LSIL+ and HSIL+) for CIN3+ diagnoses (p1=0.76, p2=0.95 and p3=0.50, respectively).ConclusionThe current OncoE6 test proved to be a point-of-care test. However, given its poor performance for CIN2+ diagnoses, we do not recommend it for primary screening. We recommend to enrich it with more oncogenic HPV types, which may improve the performance of the test akin to that of cytology.

Download Full-text

Human papillomavirus (HPV) genotypes and HPV16 variants in human immunodeficiency virus-positive Italian women

Journal of General Virology ◽

10.1099/vir.0.83553-0 ◽

2008 ◽

Vol 89 (6) ◽

pp. 1380-1389 ◽

Cited By ~ 26

Author(s):

Maria Lina Tornesello ◽

Maria Luisa Duraturo ◽

Paolo Giorgi-Rossi ◽

Matilde Sansone ◽

Roberto Piccoli ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Human Papillomavirus ◽

High Risk ◽

Hiv Positive ◽

Sequencing Analysis ◽

Hiv Positive Women ◽

Immunodeficiency Virus ◽

Hpv Genotypes ◽

Italian Women ◽

Hiv Negative

Human immunodeficiency virus (HIV)-positive women have high rates of cervical squamous intraepithelial lesions (SIL) and concurrent human papillomavirus (HPV) infections with a variety of genotypes whose oncogenic risk is poorly documented. The prevalence and persistence of HPV genotypes and HPV16 variants were analysed in 112 HIV-positive and 115 HIV-negative Italian women. HIV-positive women were more likely than HIV-negative women to be infected by HPV at the initial examination (39.3 vs 13.9 %, P<0.001) and to have a higher period prevalence of HPV infection over a 3-year follow-up (43.8 % vs 17.4 %, P<0.001), regardless of CD4+ cell counts and anti-retroviral therapy. ‘High-risk’ and ‘probable high-risk’ HPVs (types 16, 18, 31, 33, 35, 45, 52, 58 and 66), among the 20 different viral genotypes identified, were predominant in HIV-positive (33.9 %) compared with HIV-negative (13.9 %) women. Among HIV-infected women, with normal cytology as well as with SIL of any grade, the most common genotypes were HPV16 followed by HPV81, -58, -72, -33 and -62. HPV16 isolates from 18 HIV-positive and eight HIV-negative women were classified into variant lineages based on sequencing analysis of E6 and E7 genes and the long control region. Whilst the HPV16 G350 European variant was prevalent in both HIV-positive (10.7 %) and -negative women (3.5 %), HPV16 African 2 variant was only detected in HIV-positive women (3.6 %), suggesting different sexual mixing behaviours. The increased prevalence of uncommon viral genotypes and HPV16 variants in HIV-positive Italian women underscores the need to target a wide range of HPV types in cervical screening of high-risk women.

Download Full-text

Human Papillomavirus Infections in Cervical Samples From HIV-Positive Women: Evaluation of the Presence of the Nonavalent HPV Genotypes and Genetic Diversity

Frontiers in Microbiology ◽

10.3389/fmicb.2020.603657 ◽

2020 ◽

Vol 11 ◽

Author(s):

Catia Sias ◽

Valerio Guarrasi ◽

Claudia Minosse ◽

Daniele Lapa ◽

Franca Del Nonno ◽

...

Keyword(s):

Human Papillomavirus ◽

Screening Program ◽

Prediction Method ◽

Hiv Positive ◽

Low Grade ◽

Squamous Intraepithelial Lesion ◽

Hpv Dna ◽

Hiv Positive Women ◽

Intraepithelial Lesion ◽

Hpv Types

Non-nonavalent vaccine (9v) Human papillomavirus (HPV) types have been shown to have high prevalence among HIV-positive women. Here, 1444 cervical samples were tested for HPV DNA positivity. Co-infections of the 9v HPV types with other HPV types were evaluated. The HPV81 L1 and L2 genes were used to investigate the genetic variability of antigenic epitopes. HPV-positive samples were genotyped using the HPVCLART2 assay. The L1 and L2 protein sequences were analyzed using a self-optimized prediction method to predict their secondary structure. Co-occurrence probabilities of the 9v HPV types were calculated. Non9v types represented 49% of the HPV infections; 31.2% of the non9v HPV types were among the low-grade squamous intraepithelial lesion samples, and 27.3% among the high-grade squamous intraepithelial lesion samples, and several genotypes were low risk. The co-occurrence of 9v HPV types with the other genotypes was not correlated with the filogenetic distance. HPV81 showed an amino-acid substitution within the BC loop (N75Q) and the FGb loop (T315N). In the L2 protein, all of the mutations were located outside antigenic sites. The weak cross-protection of the 9v types suggests the relevance of a sustainable and effective screening program, which should be implemented by HPV DNA testing that does not include only high-risk types.

Download Full-text

Outcomes of loop electrosurgical excision procedure for cervical neoplasia in human immunodeficiency virus–infected women

International Journal of Gynecological Cancer ◽

10.1136/ijgc-00009577-200605000-00021 ◽

2006 ◽

Vol 16 (3) ◽

pp. 1082-1088

Author(s):

C. Kietpeerakool ◽

J. Srisomboon ◽

P. Suprasert ◽

C. Phongnarisorn ◽

K. Charoenkwan ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Antiretroviral Therapy ◽

Pap Smear ◽

Cervical Neoplasia ◽

Low Grade ◽

Squamous Intraepithelial Lesion ◽

Immunodeficiency Virus ◽

Intraepithelial Lesion ◽

Loop Electrosurgical Excision ◽

Loop Electrosurgical Excision Procedure

The objective of this study was to evaluate the treatment outcomes and complications in human immunodeficiency virus (HIV)–infected women undergoing loop electrosurgical excision procedure (LEEP) for cervical neoplasia. The medical record of 60 evaluable HIV-infected women who had abnormal Papanicolaou (Pap) smear and underwent LEEP following colposcopy at Chiang Mai University Hospital between May 1998 and June 2004 was reviewed. Thirty-one (51.7%) had associated genital infection at screening. Twenty-five (41.7%) had opportunistic infection, but only 18 (30.0%) were treated with antiretroviral therapy. The most common abnormal Pap smear was high-grade squamous intraepithelial lesion (46.7%), followed by low-grade squamous intraepithelial lesion (40.0%). Forty (66.7%) women had clear surgical margins after LEEP. Only one (1.7%) woman had severe intraoperative hemorrhage. Early and late postoperative hemorrhage were noted in three (5%) women of each period. Localized infection of the cervix was detected in seven (11.7%) women. Two (3.3%) women developed cervical stenosis at 6 months after LEEP. There was no significant difference in overall complications between HIV-infected women and the control group (P = 0.24). Among 60 HIV-infected women, no statistical difference in the rate of margins involvement (P = 1.00) and complications (P = 0.85) could be demonstrated between HIV-infected women who received antiretroviral therapy and those who did not. Disease-free rate at 6 and 12 months were 97.1% and 88%, respectively. These data demonstrated that LEEP appears to be safe and effective in HIV-infected women.

Download Full-text

CERVICAL SMEAR ABNORMALITIES IN HIV INFECTED WOMEN ATTENDING A RURAL HOSPITAL ART CENTER IN TAMILNADU

10.36106/gjra/0100730 ◽

2020 ◽

pp. 16-17

Author(s):

Jeya Pratheef Muthiah ◽

Mareeswari. M

Keyword(s):

Pap Smear ◽

Cd4 Count ◽

Reproductive Age ◽

Hiv Positive ◽

Cd4 Counts ◽

Papanicolaou Smear ◽

Immunological Status ◽

Smear Examination ◽

Hiv Positive Women ◽

Art Program

INTRODUCTION: Cervical cancers are the most common form of cancer encountered in Indian women. Studies from India had reported HIV positive women are 10-11 times more prone for cervical carcinomas than HIV negative women with a recent rise in incidence observed. India started a free antiretroviral therapy (ART) program in 2004 with services extended to rural General Hospitals. Cancer cervix can be diagnosed at a preinvasive stage with repeatative papanicolaou smear (cytological screening) and can be readily preventable. AIM: Our aim is to determine the prevalence of PAP smear abnormalities among HIV infected women from rural areas coming for ART initiation and the relationship between immunological status and smear abnormalities. METHODS: As per the Indian National ART program all HIV positive women of reproductive age should undergo PAP smear examination before initiation of ART. All consenting women >18 years of age with history of penetrative vaginal intercourse undergo PAP smear examination. In this observational cohort from 25th June 2011 to 15th January 2012 conducted in Melur ART centre and the cytological reports and the patient clinical and immunological status data was analyzed by using SPSS 17 version. RESULTS: 102 PAP smears were obtained and classified according to Bethesda classification. Five patients (4.90%) were abnormal. Squamous cell carcinoma was observed in 1 (0.98%) patient with a CD4 count of 580 cells/mm3. High squamous intraepithelial lesions were observed in 2 patients (1.96%) with CD4 counts of 208 & 633 cells/mm3 respectively. Low squamous intraepithelial lesion were observed in 2 patients (1.96%) with CD4 counts of 50 and 385 respectively cells/mm3. Immunological status (CD4 count) correlated with grade of the initial lesion (p=0.10). All the patients with PAP smear abnormalities were referred to Madurai Medical College Hospital for further treatment and follow-up. CONCLUSION: In our observational study increasing cytological abnormalities in the HIV Infected women were noted. Accordingly, all ART centre and HIV treatment programs should institute comprehensive reproductive health care services for this high-risk groups, including routine Papanicolaou smear screening

Download Full-text

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.

Download Full-text

Low Utility in Colposcopy-directed Biopsies for Non-high Grade Cytological Abnormalities on PAP Smear

Current Women s Health Reviews ◽

10.2174/1573404815666190821093421 ◽

2020 ◽

Vol 16 (1) ◽

pp. 18-22

Author(s):

Eronmwon E. Gbinigie ◽

Joshua Fogel ◽

Maggie Tetrokalashvili

Keyword(s):

Pap Smear ◽

Multinomial Logistic Regression ◽

Cervical Dysplasia ◽

Outcome Variable ◽

Low Grade ◽

High Grade ◽

Squamous Intraepithelial Lesion ◽

Intraepithelial Lesion ◽

Cytologic Abnormalities ◽

Cytology Screening

Background: Clinicians commonly perform colposcopy directed biopsies on patients with low grade squamous intraepithelial lesion (LSIL) on PAP cytology even when not consistent with clinical guidelines. Objective: We study the association of PAP cytology screening results with cervical intra-epithelia neoplasia (CIN) 2-3 high-grade dysplasia, as confirmed by colposcopy-directed biopsy. Methods: A retrospective study of 263 women with an abnormality on the PAP smear. Multinomial logistic regression was performed with predictors of PAP cytology screening results with the outcome variable of colposcopy-directed biopsy. Results: High grade squamous intraepithelial lesion (HSIL) had significantly increased relative risk for CIN 2-3 (RR: 9.85, 95% CI: 1.84, 52.79, p=0.008). LSIL was not significantly associated with CIN 2-3. In the comparisons of negative with CIN-1, both HSIL and LSIL were not significantly associated with a negative biopsy. Conclusion: HSIL is associated with cervical dysplasia of CIN 2-3 while LSIL is not associated with cervical dysplasia of CIN 2-3. We do not recommend routine biopsies in patients with LSIL cytologic abnormalities unless additional compelling factors exist.

Download Full-text

High prevalence of human papillomavirus and European variants of HPV 16 infecting concomitantly to cervix and oral cavity in HIV positive women

PLoS ONE ◽

10.1371/journal.pone.0227900 ◽

2020 ◽

Vol 15 (4) ◽

pp. e0227900

Author(s):

Milagros Pérez-Quintanilla ◽

Rocío Méndez-Martínez ◽

Salvador Vázquez-Vega ◽

Raquel Espinosa-Romero ◽

Rita Sotelo-Regil ◽

...

Keyword(s):

Human Papillomavirus ◽

Oral Cavity ◽

Hiv Positive ◽

Hpv 16 ◽

Hiv Positive Women ◽

High Prevalence

Download Full-text

Profiles of Human Papillomavirus Detection of the Multinucleated Cells in Cervical Smears

Microorganisms ◽

10.3390/microorganisms9081575 ◽

2021 ◽

Vol 9 (8) ◽

pp. 1575

Author(s):

Kaori Okayama ◽

Toshiyuki Sasagawa ◽

Koji Teruya ◽

Mizue Oda ◽

Masahiko Fujii ◽

...

Keyword(s):

Pap Smear ◽

Morphological Changes ◽

Human Papillomaviruses ◽

Multinucleated Cells ◽

Hpv Genotypes ◽

Atypical Cells ◽

Intraepithelial Lesion ◽

Liquid Based Cytology ◽

Cervical Cells ◽

High Risk Hpv

Many genotypes of human papillomaviruses (HPVs) may lead to morphological changes in cells, resulting in various atypical cells, such as multinucleated cells (MNCs) and koilocytes, in the cervix. However, the relationships between the profiles of HPV genotypes and MNCs are not exactly known. Thus, this study comprehensively profiles the HPV genotypes in MNCs using a microdissection method. HPV genotypes and MNCs were detected in 651 cases with an abnormal Pap smear by liquid-based cytology. Specific HPV genotypes were also detected, including HPV16, 34, and 56, which might be associated with MNCs. This result suggests that the high-risk HPV genotypes, such as HPV16 and 56, are associated with the atypical changes in MNC morphology from normal cervical cells. The results also show that MNCs may be a predictor of squamous intraepithelial lesion.

Download Full-text