Prediction of Recurrent and Residual Cervical Dysplasia by Human Papillomavirus Detection among Patients with Abnormal Cytology

doi:10.1006/gyno.1998.5250

Gynecologic Oncology

Volume 72, Issue 2, February 1999, Pages 199-201

https://doi.org/10.1006/gyno.1998.5250 Get rights and content

Abstract

To determine the discriminative capacity of human papillomavirus (HPV) DNA testing for recurrent and residual cervical dysplasia, 43 patients with abnormal cytology after treatment for cervical dysplasia were tested for the presence of HPV DNA by PCR. An endocervical curettage was performed in all patients for histological examination. Sixteen of the 43 patients showed moderate or severe dysplasia. The HPV test was positive in all 16 patients with recurrent or residual dysplasia and negative in 12 of the 27 patients without dysplasia. The sensitivity and specificity of the HPV test were 100 and 44%, respectively. The likelihood ratio of a positive HPV test was 1.8, whereas a negative HPV test had a likelihood ratio of 0.12. Testing for the presence of HPV has the potential to select patients without recurrent or residual cervical dysplasia who have an abnormal cytological smear. This may have clinical implications, since unnecessary diagnostic conizations may be avoided in patients with abnormal cytology after treatment for cervical dysplasia and a negative HPV test.

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Cited by (79)

Study of high-risk hpv infection clearance after conization
2021, Clinica e Investigacion en Ginecologia y Obstetricia
Evaluar el porcentaje de aclaramiento de la infección por el virus del papiloma humano (VPH) de alto riesgo en las mujeres sometidas a una conización cervical, así como analizar los genotipos de VPH más prevalentes en nuestro medio.
Estudio longitudinal, observacional, retrospectivo, descriptivo y analítico. Se revisaron las conizaciones realizadas en el Área 7 del Hospital Clínico San Carlos de Madrid entre octubre de 2015 y octubre de 2016.
De 291 conizaciones practicadas durante 12 meses, se realizó determinación de VPH-AR pre-conización a 138 pacientes. En 247 pacientes la indicación del tratamiento escisional fue por resultado de biopsia HSIL/CIN 2-3, y en 44 por LSIL/CIN una persistente más de dos años. Sesenta y una de las 138 mujeres presentaron uno o varios VPH-AR distintos al 16/18/31 antes de la conización (61/138), mientras que en 77 pacientes se diagnosticaron VPH-AR 16/18/31 (77/138). Si desglosamos, el VPH 16 estuvo presente en 58/138 de los casos, el VPH 31 en 15/138 y el VPH 18 en 4/138. En el primer control post-conización, en 126 pacientes la determinación de VPH-AR fue negativa (126/138). El VPH 16 se aclaró en 49 pacientes (49/58), el VPH 31 en 15 (15/15) y el VPH 18 en uno (1/4).
El genotipo 16 fue el VPH-AR más frecuente en mujeres conizadas en nuestro estudio, seguido por el 31 y el 18. Tras la conización cervical, se consigue un aclaramiento de la infección por VPH-AR en un 91,4% de las pacientes.
To evaluate the percentage of clearance of high-risk HPV infection in women undergoing cervical conization, as well as to analyse the most prevalent HPV genotypes in our environment.
Longitudinal, observational, retrospective, descriptive and analytical study. The conizations performed in Area 7 of the Hospital Clínico San Carlos in Madrid between October 2015 and October 2016 were reviewed.
Of 291 conizations over 12 months, pre-conization HPV-AR determination was made in 138 patients. In 247 patients the indication for excisional treatment was the result of biopsy HSIL/CIN 2-3, and in 44 for persistent LSIL/CIN 1 for more than 2 years. Sixty-one of the 138 women had one or more HPV-AR other than 16/18/31 prior to conization (61/138), while 77 patients were diagnosed with HPV-AR 16/18/31 (77/138). If we break it down, HPV 16 was present in 58/138 of cases, HPV 31 in 15/138 and HPV 18 in 4/138. In the first post-conization control, in 126 patients the determination of HPV-AR was negative (126/138). Clearance of HPV 16 was achieved in 49 patients (49/58), HPV 31 in 13 (13/15) and HPV 18 in 1 (1/4).
Genotype 16 was the most common HPV-AR in conized women in our study, followed by 31 and 18. After cervical conization, a clearance of HPV-AR infection was achieved in 91.4% of patients.
Value of endocervical margin and high-risk human papillomavirus status after conization for high-grade cervical intraepithelial neoplasia, adenocarcinoma in situ, and microinvasive carcinoma of the uterine cervix
2014, Gynecologic Oncology
Citation Excerpt :
Colposcopy with directed biopsy has been shown to miss residual/recurrent lesions [3]. In addition, the Papanicolaou (Pap) test has some inherent flaws due to its relatively high rate of false negativity and low sensitivity after the conization [4,5]. Therefore, annual cervical cytology accompanied by human papillomavirus (HPV) testing at 12 and 24 months has been recently used to monitor for women treated for high-grade CIN because high-risk (HR)-HPV assessment is beneficial in identifying the undetected high-grade residual/recurrent disease [6].
The aim of this study was to analyze clinico-pathologic factors and the optimal cut-off value of high-risk human papillomavirus (HR-HPV) viral load for predicting high-grade residual/recurrent disease after the conization in cervical intraepithelial neoplasia (CIN 2–3), adenocarcinoma in situ (AIS), and microinvasive carcinoma of the uterine cervix (MICA).
We retrospectively reviewed data from 701 patients with CIN 2–3, AIS, and MICA who underwent conization between September 2003 and June 2012. Receiver-operating characteristic curve analysis was used to find out the cut-off value of HR-HPV viral load for predicting residual/recurrent disease. Clinico-pathologic variables, including resection margin and HR-HPV status, were evaluated as possible predictors of residual/recurrent disease.
At a cut-off value of 1.16 RLU/CO for post-cone HR-HPV viral load, the sensitivity was 88.2% and the specificity was 98.3%. Multivariate analysis demonstrated that post-cone cytology (p = 0.001, OR = 83.808, 95% CI = 6.688–1050.232), endocervical margin status (p < 0.001, OR = 80.478, 95% CI = 7.421–872.732), and post-cone HR-HPV status (p < 0.001, OR = 79.660, 95% CI = 8.539–743.129) were significantly associated with residual/recurrent disease. The post-cone HR-HPV positivity was observed more in the patients who showed positive endocervical margin than in the patients with positive ectocervical margin (32.6% vs. 5.3%, p = 0.002).
Follow-up using liquid based cytology in combination with HR-HPV test at 12 months after the conization, and not the early HR-HPV test, might be acceptable. Post-cone endocervical margin status combined with post-cone HR-HPV test is critical for predicting residual/recurrent disease and clinical management.
Assessment of HPV-mRNA test to predict recurrent disease in patients previously treated for CIN 2/3
2014, Journal of Clinical Virology
The use of HPV-mRNA test in the follow-up after LEEP is still matter of debate, with regard to its capacity of prediction relapse.
The aim of the present study is to evaluate the reliability of HPV-mRNA test to predict the residual and recurrent disease, and its accuracy in the follow-up of patients treated for CIN 2/3.
Multicenter prospective cohort study. Patients who underwent LEEP after a biopsy diagnosing CIN 2/3 were followed at 3, 6, 12, 24 and 36 months. Each check up included cytology, colposcopy, HPV-DNA test (LiPA) and HPV-mRNA test (PreTect HPV Proofer Kit NorChip). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), of HPV-DNA test and HPV-mRNA test to predict relapse, recurrent and residual disease. Using multiple logistic regression, the statistical significant variables as assessed in univariate analysis were entered and investigated as predictors of relapse disease.
The mRNA-test in predicting a residual disease had a sensitivity of 52% and a NPV of 91%, whereas DNA-test had 100% and 100%, respectively. On the contrary in the prediction of recurrent disease mRNA-test had a sensitivity and a NPV of 73.5% and 97%, whereas DNA-test had 44% and 93%. On the multivariate analysis, age, cytology, HPV DNA and mRNA test achieved the role of independent predictors of relapse.
HPV-mRNA test has a higher sensitivity and a higher NPV in predicting recurrent disease, for this reason it should be used in the follow-up of patients treated with LEEP for CIN 2/3 in order to individualize the timing of check up.
The incidence of human papillomavirus infection following treatment for cervical neoplasia: A systematic review
2014, Gynecologic Oncology
To systematically review the published literature in order to estimate the incidence and describe the variability of human papillomavirus (HPV) infection in women following treatment for cervical neoplasia.
Several scientific literature databases (e.g. PubMed, ISI Web of Science) were searched through January 31, 2012. Eligible articles provided data on (i) baseline HPV infection status within 6 months prior to or at time of treatment (pre-treatment); and (ii) HPV test results for women's first visit after treatment occurring within 36 months (post-treatment). We abstracted and summarized the post-treatment incidence of newly detected HPV genotypes that were not present at pre-treatment, overall and stratified by study and other population characteristics.
A total of 25 studies were included, reporting post-treatment HPV incidence in nearly 2000 women. Mean patient age ranged from 31 to 43 years (median 36). Most studies used cervical exfoliated cell specimens to test for HPV DNA (n = 20; 80%), using polymerase chain reaction (n = 21; 84%). Cervical neoplasia treatment included loop electrical excision procedure (n = 11; 44%); laser conization (n = 2; 8%); laser ablation, surgical conization, cryotherapy, alpha-interferon (n = 1; 4% each); or multiple treatment regimens (n = 8; 32%). Follow-up times post-treatment ranged from 1.5 to 36 months (median 6). More than half of studies (n = 17; 68%) estimated the incidence of any HPV type following treatment, while 7 (28%) focused specifically on high-risk (HR) HPV. HPV incidence after treatment varied widely, ranging from 0 to 47% (interquartile range: 0%-15%) in up to 3 years of follow-up after treatment. Lower HPV incidence was observed among studies that included relatively younger women, used laser conization, focused on HR-HPV rather than overall HPV infection, and had a lower proportion of recurrent cervical disease.
These modest summary incidence estimates from the published literature can guide clinicians, epidemiologists and health economists in developing best practices for post-treatment cervical cancer prevention.
Follow-up after LLETZ: A study of 682 cases of CIN 2-CIN 3 in a single institution
2012, European Journal of Obstetrics and Gynecology and Reproductive Biology
Citation Excerpt :
A total of 25% of the patients had a positive HPV test at the follow-up at 6 months. The rate of persistent HPV infection after therapeutic conization is between 6% and 61% depending on the methods used to detect HPV DNA, the type of treatment and the time between treatment and evaluation [13,22,24]. Houfflin-Debarge et al. observed a 34% rate of persistent HPV infection 3 months after treatment.
To evaluate the importance of resection margins in the risk of persistent/recurrent lesions and to investigate other factors such as detection of high-risk HPV, which could potentially predict persistent/recurrent disease before patients engage in follow-up.
682 women with a histologically confirmed diagnosis of CIN 2–3 treated by loop electrosurgical excision procedure (LEEP) were included, between January 2000 and December 2006. Age, high-risk HPV detection determined by Hybrid Capture II and cone margins were evaluated as possible predictors of persistent/recurrent disease.
The mean age at diagnosis was 37.8 years (range 18–73). The mean follow-up period was 39.9 months (SD 25.8). 6.6% of patients (45/682) were lost to follow-up. 64.7% of patients (441/682) had clear margins in the specimen and 20.1% of patients had positive surgical margins (137/682). In 8.6% of patients (59/682) the resection margins were uncertain. Positive endocervical sweep was found in 10.8% of cases (73/682). Residual/recurrent disease was demonstrated by colposcopy-guided biopsy in 13.9% of patients (88/637); 77.3% (68/88) of them developed CIN 1 while only 22.7% (20/88) developed high-grade premalignant lesions or carcinomas during the follow-up. We found significant differences in the frequency of persistent/recurrent disease depending on the status of margins: 24.8% of cases with positive margins vs 11.1% of cases with negative margins (p < 0.0001). Multivariate analysis showed that only post-treatment high-risk HPV detection and status of the cone margins were significantly predictive of persistent/recurrent disease (OR 4.1, 95%CI 2.4–7.3, p < 0.0001 and OR 2.7, 95%CI 1.5–4.7, p = 0.001; respectively).
The combination of histological examination of resection margins plus post-treatment tests for HPV detection would help to classify LEEP-treated patients into categories at different risk of recurrence.
Predictors of recurrence in high-grade cervical lesions and a plan of management
2010, European Journal of Surgical Oncology
Positive endocervical margins are an important predictor of recurrence in high-grade cervical lesions, and though they do not always warrant retreatment, closer surveillance is recommended.
To identify predictors of recurrence and persistence of high-grade cervical dysplasia and to determine appropriate follow-up. Design: prospective pilot study. Setting: Gynaecological surgical center.
Three hundred fifty-two patients were treated between 1999 and 2002 for high-grade lesions.
According to the accessibility of the transformation zone and the degree of dysplasia, patients were treated either by conization or by loop electrosurgical excision procedure (LEEP). Follow-up comprised colposcopy and Pap-smear screening 4–6 months after treatment as well as high-risk human papillomavirus (HR-HPV) testing before and after treatment.
underscore predictors of recurrence and propose a treatment flowchart for both management and follow-up.
Of the 352 patients, 37 (10.5%) had true recurrence 6 months after initial surgical treatment and 6 patients (1.7%) had persistent lesions. Overall, 43 patients (12.2%) were considered as having recurrent disease. Patients were followed up for 5 years with a mean of 73 months. The most important predictor of recurrence was a positive HR-HPV test at 6 months postoperatively (odds ratio 38.8, 95% confidence interval 14.09, 107.05). The second significant predictor was positive endocervical margins and the third was positive pre-treatment HPV typing. A positive post-treatment HPV test had a more significant influence on risk than a positive test before treatment.
In agreement with recent findings, our study supports the usefulness of the HR-HPV test in the follow-up of treated high-grade lesions, especially when excision margins were positive.

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¹: To whom correspondence and reprint requests should be addressed at the Department of Virology, Academic Medical Center, Building L1, Room 158, Meibergdreef 15, 1105 A2 Amsterdam, The Netherlands. Fax: 31206979271.

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Regular ArticlePrediction of Recurrent and Residual Cervical Dysplasia by Human Papillomavirus Detection among Patients with Abnormal Cytology

Abstract

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Gynecol Oncol

Am J Obstet Gynecol

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Regular Article
Prediction of Recurrent and Residual Cervical Dysplasia by Human Papillomavirus Detection among Patients with Abnormal Cytology