Risk of high-grade squamous intraepithelial lesions (HSIL) in patients with abnormal cytology and HPV-DNA negative results

Objective: A vast majority of cervicovaginal intraepithelial lesions are caused by high-risk human papillomaviruses (HPVs). The Pap test has been the sole method used for the screening of cervicovaginal squamous intraepithelial lesions (SIL). Recently, the FDA approved an HPV-DNA assay as a method of primary screening. We report on a series of FDA-approved HPV-DNA test-negative SIL with HPV genotyping, using an alternative method on the corresponding surgical biopsy specimens. Study Design: A retrospective review identified cytology-positive HPV-negative cases over a 15-month period at a tertiary care gynecologic oncology institution. Corresponding biopsies were reviewed and genotyped for high-risk HPVs. Results: Of the 18,200 total cases, 17 patients meeting the study criteria were selected with 27 surgical specimens corresponding to their cytologic diagnoses. Four patients with high-grade lesions were identified, 3 of whom (75%) were positive for HPV. One of these 4 patients (25%) showed high-grade SIL on biopsies from 4 separate sites in the cervix and vagina. Multiviral HPV infections were frequent. Conclusions: We discuss the relevance of cotesting for screening cervical SILs and emphasize that false-negative results are possible with the FDA-approved HPV screening assay, also in patients with high-grade SIL. These cases may be detectable by cytologic examination and this suggests that the Pap test remains an important diagnostic tool.

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8. Human papillomavirus mRNA testing for the detection of anal high-grade squamous intraepithelial lesions in HIV-positive men who have sex with men

Sexual Health ◽

10.1071/shv10n6ab8 ◽

2013 ◽

Vol 10 (6) ◽

pp. 573

Author(s):

Elena Sendagorta Cudós ◽

Maria P. Romero Gomez ◽

Beatriz Hernandez Novoa ◽

Ander Mayor ◽

Jose I. Bernardino De La Serna ◽

...

Keyword(s):

Predictive Value ◽

Screening Program ◽

University Hospital ◽

High Grade ◽

Squamous Intraepithelial Lesions ◽

Cross Sectional ◽

Hpv Dna ◽

Hpv E6 ◽

Anal Cytology ◽

Intraepithelial Lesions

Background Currently, screening for anal high-grade squamous intraepithelial lesions (HSIL) relies on anal cytology and high-resolution anoscopy (HRA). Since this approach has limited sensitivity and specificity for detecting anal HSIL, there is increasing interest in the role of biomarkers for predicting anal HSIL. The aim of this study is to evaluate the diagnostic accuracy of HPV E6/E7-mRNA expression for the detection of anal HSIL in MSM HIV-infected patients, in comparison to DNA-HR-HPV and anal cytology. Methods: This cross-sectional screening study included 101 MSM followed at the HIV-unit of La Paz University Hospital. Intra-anal swabs from patients participating in a screening program including cytology, HRA and histology were analysed. HR-HPV-DNA detection was performed by means of the CLART HPV2 assay (GENOMICA SAU.). E6/E7-mRNA detection of HR-HPV types 16, 18, 31, 33 and 45 was performed using the NucliSENS-EasyQ assay (BioMérieux, Marcy l’Etoile, France). Results: HR-HPV DNA and HPV E6/E7 mRNA were detected in 82% and 57% of the anal smears, respectively. Anal cytology screening was abnormal in 70.3%. For the detection of HSIL sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 71.7%, 55.6%, 57.9%, and 69.8% for E6/E7-mRNA testing, respectively, compared with 97.9%, 31.5%, 55.4% and 94.4%, respectively, for HR-HPV DNA testing and 83%, 40.7%, 54.9%, 73.3%, respectively, for cytology testing. Conclusions: In comparison with the other tests, the NucliSENS EasyQ HPV assay yielded a lower clinical sensitivity but a higher clinical specificity and PPV for the detection of anal HSIL in MSM HIV-infected patients.

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32. HPV type and strain variant concordance between anal cancers and their preceding high-grade squamous intraepithelial lesions

Sexual Health ◽

10.1071/shv10n6ab32 ◽

2013 ◽

Vol 10 (6) ◽

pp. 585

Author(s):

Joel Palefsky ◽

Maria Da Costa ◽

Teresa M. Darragh ◽

Naomi Jay ◽

J. Michael Berry

Keyword(s):

Anal Cancer ◽

High Grade ◽

Squamous Intraepithelial Lesions ◽

Hpv 16 ◽

Hpv Dna ◽

Formalin Fixed Paraffin ◽

Formalin Fixed Paraffin Embedded ◽

Location Methods ◽

Intraepithelial Lesions

Background Anal high-grade squamous intraepithelial lesions (HSIL) are frequently found overlying anal cancer on histology, and anal cancer has been observed to develop in the same location as previously diagnosed anal HSIL. These observations support the role of HSIL as the direct precursor lesion to anal cancer. To further investigate a direct pathogenetic relationship between anal HSIL and cancer, we typed and sequenced HPV DNA in anal HSIL and the cancers that subsequently developed in the same location. Methods: Tissues samples were analysed from 15 HIV-infected men followed at UCSF in whom anal cancer developed at a previously biopsied site of HSIL. Formalin-fixed paraffin-embedded pairs of HSIL and cancer were typed for HPV DNA using L1 PCR. HPV 16-positive samples underwent E6-based strain variant analysis. Results: Nine matched pairs for which DNA from both HSIL and cancer were available were analysed. Eight pairs (89%) contained HPV 16 DNA. One (11%) contained both HPV 18 and 51 in both samples. Of the eight HPV 16-positive pairs, each pair contained the same HPV 16 strain variant. Four contained the Eur-350T variant alone, and one contained Eur-350T in both the HSIL and cancer, with an additional 426T variant in the cancer. One pair contained both Eur-350T and 457C in both the HSIL and the cancer. Two pairs contained the Eur-350G variant alone. Conclusions: Concordance of both the HPV type and strain variant in anal cancers and their site-matched preceding HSIL further supports the role of anal HSIL as an anal cancer precursor.

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Human papillomaviruses 16 and 58 are distributed widely among women living in Shanghai, China, with high-grade, squamous intraepithelial lesions

Epidemiology and Infection ◽

10.1017/s0950268818003011 ◽

2018 ◽

Vol 147 ◽

Cited By ~ 2

Author(s):

J. Xu ◽

Z. Xia ◽

L. Wang ◽

B. Yang ◽

Y. Zhu ◽

...

Keyword(s):

Human Papillomaviruses ◽

Low Grade ◽

High Grade ◽

Squamous Intraepithelial Lesions ◽

Hpv 16 ◽

Hpv Dna ◽

Control And Prevention ◽

Intraepithelial Lesion ◽

Hpv Dna Tests ◽

Intraepithelial Lesions

AbstractThe distribution of human papillomaviruses (HPVs) must be understood for the control and prevention of cervical cancer. Community-based Papanicolaou and HPV DNA tests were performed on 41 578 women. The prevalences of HPV genotypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68 were assessed. In total, 10% women were infected/co-infected by these HPVs. The infection rate increased from 7.1% in women aged ⩽30 years to 10.4% in those aged 50–60 years, and then decreased slightly to 9.9% in those aged >60 years. The HPV 16 and 58 positivity rates were significantly higher among women with high-grade squamous intraepithelial lesions (HSILs) than among those with cervicitis/negativity for intraepithelial lesion or malignancy (NILM) or low-grade SILs (LSILs). The HPV 18, 52 and 68 infection rates were significantly lower in women with HSILs than in those with NILM or LSILs. The proportion of women infected by multiple HPV strains was higher among those with HSILs. The proportions of the five most common genotypes, HPV 16, 18, 33, 52 and 58, increased with the number of co-infecting strains. HPV 16 and 58 were the high-risk HPVs in the Shanghai community and should be the focus in HPV screening and vaccination.

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Anogenital warts contributing to the risk of squamous intraepithelial lesions among HIV-positive women of São Paulo, Brazil

International Journal of STD & AIDS ◽

10.1258/095646203321605503 ◽

2003 ◽

Vol 14 (5) ◽

pp. 309-313 ◽

Cited By ~ 2

Author(s):

Maria Alice G Goncalves ◽

Marcelo N Burattini ◽

Eduardo A Donadi ◽

Eduardo Massad

Keyword(s):

Univariate Analysis ◽

Hpv Infection ◽

Hiv Positive ◽

High Grade ◽

Anogenital Warts ◽

Squamous Intraepithelial Lesions ◽

Cross Sectional ◽

Hpv Dna ◽

Hiv Positive Women ◽

Intraepithelial Lesions

Unsafe sexual practices may expose HIV-positive women to high-grade squamous intraepithelial lesions (SIL) and to infection with oncogenic human papillomavirus (HPV) types. A cross sectional study of 141 HIV-positive women was designed to evaluate risk factors for the development of cervico-vaginal SIL and HPV-DNA detection/typing. Uni- and multivariate forward stepwise analysis was used to determine the relationship between risk variables and HPV infection and between risk behaviour, HPV and HIV infection with development of SIL. Univariate analysis showed that HPV-DNA infection was related to previous and recurrent anogenital warts, male genital warts and cytological alteration. For final multivariate analysis, both HPV type (undetermined- and high-risk, OR=29.3 and 112.0, respectively) were statistically associated ( P=0.019) with high-grade cervico-vaginal SIL. The presence of anogenital warts as well as high- and undetermined-risk HPV infection may alert to cyto/histopathological alterations. These results point out the importance of the use of barrier methods and routine early genitoscopy/treatment for HIV-infected partners.

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Increased risk for development of severe cervical dysplasia among postmenopausal women with normal cytology and presence of HPV mRNA

10.21203/rs.2.22222/v1 ◽

2020 ◽

Author(s):

Katrin Christine Asciutto ◽

Christer Borgfeldt ◽

Ola Forslund

Keyword(s):

Postmenopausal Women ◽

Cervical Dysplasia ◽

Low Grade ◽

Squamous Intraepithelial Lesions ◽

Abnormal Cytology ◽

Normal Cytology ◽

Hpv Dna ◽

Increased Risk ◽

Intraepithelial Lesions ◽

Hpv Mrna

Abstract Background: During 2013 and 2016 the Region of Skåne, Sweden, started to analyse human papillomavirus (HPV) and cytology in postmenopausal women 60-65 years of age. Our aim was to evaluate if the presence of high-risk (HR) HPV mRNA could predict the development of cervical abnormalities among HR-HPV DNA positive women with normal cytology. Methods: A total of 271 women, 60-65 years of age, underwent liquid based cytology (LBC) and HPV testing by using the HR-HPV DNA MGP-PCR-Luminex assay. HR-HPV DNA-positive women with normal cytology underwent complimentary HPV mRNA testing (Aptima, Hologic). Over a period of 49 months (SD 11.0) the women received regular follow-up at intervals of 12-18 months. Women with abnormal cytology and/or a positive HR-HPV result at two subsequent visits were scheduled for colposcopy and clinical examination. Results: Over the surveillance period, 3.6% (10/271) of the HR-HPV DNA positive women developed histologically confirmed high-grade squamous intraepithelial lesions (HSILs) or worse and 13.3% (36/271) were diagnosed with cervical atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesions (LSILs). The cumulative incidence rates (CIR) were 29.7% (CI 24.8-30.1) for HSIL or worse among HPV mRNA-positive women at enrolment (39.4% 107/271) and 0% among HPV mRNA negative women (60.5%, 164/271), (p=0.002). The corresponding CIRs for ASCUS and LSIL was 59.9% (95% CI 59.3-66.2) and 26.1% (95 %CI 16.5-35.9), (p=0.001). Conclusions : Postmenopausal women with normal cytology along with presence of HR-HPV mRNA are at increased risk for development of severe cervical dysplasia, in contrast to those women with negative HR-HPV mRNA.

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Association of human papillomavirus and bacterial vaginosis with increased risk of high-grade squamous intraepithelial cervical lesions

International Journal of Gynecological Cancer ◽

10.1136/ijgc-2018-000076 ◽

2019 ◽

Vol 29 (2) ◽

pp. 242-249 ◽

Cited By ~ 6

Author(s):

Tamy Tiemi Suehiro ◽

Natália Malaguti ◽

Edilson Damke ◽

Nelson Shozo Uchimura ◽

Fabrícia Gimenes ◽

...

Keyword(s):

Cervical Cancer ◽

High Risk ◽

Bacterial Vaginosis ◽

Low Grade ◽

High Grade ◽

Squamous Intraepithelial Lesions ◽

Hpv Dna ◽

Increased Risk ◽

High Risk Hpv ◽

Intraepithelial Lesions

ObjectiveTo assess the rates of co-infections between human papillomavirus (HPV) and 13 key markers of bacterial vaginosis in cervical samples by multiplex polymerase chain reaction in a population with a high rate of abnormal cytology and a positive HPV test.MethodsThe study included a total of 213 women aged 18–72 years screened using Papanicolaou smears for determining cervical abnormalities and for HPV and bacterial vaginosis by single-target and multiplex polymerase chain reaction.ResultsA total of 83 (39%) women were negative for intraepithelial lesion or malignancy cytology and 130 (61%) had abnormal cytology. HPV-DNA prevalence was 69.9% and bacterial vaginosis was 72.7 %. Co-infections between bacterial vaginosis with HPV-DNA and high-risk HPV were associated with an increased risk for squamous intraepithelial lesions of low-grade cytology and high-grade squamous intraepithelial lesions plus cervical cancer. The most frequent bacterial vaginosis agent was Gardnerella vaginalis (33.8%), and co-infection with HPV-DNA and high-risk HPV increased the risk for squamous intraepithelial lesions of low grade cytology and high-grade squamous intraepithelial lesions plus cervical cancer. Co-infection between Megasphaera type I and high-risk HPV increased the risk for high-grade squamous intraepithelial lesions plus cervical cancer.ConclusionsOur results reinforce the hypothesis that some bacterial vaginosis agents may play a role as co-factors in HPV-mediated cervical carcinogenesis, at least in some populations.

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