Rate of human papillomavirus clearance after treatment of cervical intraepithelial neoplasia

doi:10.1016/S0029-7844(02)02280-9

Obstetrics & Gynecology

Volume 100, Issue 5, Part 1, November 2002, Pages 965-971

https://doi.org/10.1016/S0029-7844(02)02280-9 Get rights and content

Abstract

OBJECTIVE:

To investigate the rate of clearance of human papillomavirus (HPV) infection after surgical treatment for cervical intraepithelial neoplasia (CIN).

METHODS:

One hundred nine women with CIN I–III, treated with cryosurgery or conization at a university hospital, were observed with cervical HPV deoxyribonucleic acid (DNA) testing by general primer polymerase chain reaction and HPV typing at 0, 3, 6, 9, 12, and 24 months after treatment. Penile HPV DNA was analyzed from current sexual partners.

RESULTS:

Eighty-one percent of evaluable women were HPV DNA positive at treatment or enrollment. One year later, seven women (9%) remained positive for the same HPV type. Most women had cleared the HPV infection diagnosed at treatment within 3 months. The cryotherapy group had lower CIN grades, was younger, and had a slower HPV clearance rate (P < .002). Only four couples had HPV DNA of the same type detected.

CONCLUSION:

Surgical treatment of CIN usually results in clearance of HPV infection within 3 months. Human papillomavirus DNA testing may be useful as a rapid intermediate end point for monitoring the efficacy of treatments.

Section snippets

Materials and methods

The institutional review board of Huddinge Hospital approved the study (decision no. 126/95).

For maximum generalizability, all women admitted to the Department of Gynecology and Obstetrics, Huddinge University Hospital, Stockholm, Sweden, for treatment of CIN I–III (66 women with CIN III, 21 with CIN II, and 22 with CIN I) from September 1995 to September 1997 and giving informed consent were eligible to be enrolled. There was no HIV screening. The CIN diagnosis was based on diagnostic biopsy

Results

One hundred nine women (mean age 32.5 years, range 20–71) were enrolled in the study. These women were sampled before treatment of CIN, and 104 women had an adequate β-globin-positive sample. Twenty of 104 women (19%) were negative for HPV DNA. Six of these women became HPV positive in at least one visit during follow-up.

Among the 84 women with positive HPV DNA tests, 18 double infections were detected, giving a total of 102 cervical infections. Human papillomaviruses 16, 18, and 31 were by far

Discussion

The objective of the present study was not to investigate whether HPV infection causes CIN III, as this is already well known, but to investigate whether HPV can be cleared after treatment and at what rate. Clearance of HPV DNA was rapid and usually occurred within 3 months after treatment. Our mean length of follow-up was only 16 months, but there were few additional clearances occurring after 6 months. HPV DNA clearance was primarily found in the conization group, suggesting that this type of

References (23)

M.A.E Nobbenhuis et al.
Relation of human papillomavirus status to cervical lesions and consequences for cervical-cancer screeningA prospective study
Lancet
(1999)
K Elfgren et al.
Conization for cervical intraepithelial neoplasia is followed by disappearance of human papillomavirus deoxyribonucleic acid and a decline in serum and cervical mucus antibodies against human papillomavirus antigens
Am J Obstet Gynecol
(1996)
L Kjellberg et al.
Regular disappearance of the human papillomavirus genome after conization of cervical epithelial dysplasia by carbon dioxide laser
Am J Obstet Gynecol
(2000)
Y Nagai et al.
Persistence of human papillomavirus infection after therapeutic conization for CIN 3Is it an alarm for disease recurrence?
Gynecol Oncol
(2000)
K.L Chua et al.
Human papillomavirus analysis as a prognostic marker following conization of the cervix uteri
Gynecol Oncol
(1997)
J.E Tate et al.
Absence of papillomavirus DNA in normal tissue adjacent to most cervical intraepithelial neoplasms
Obstet Gynecol
(1996)
M Parkin et al.
Estimates of the worldwide incidence of 25 major cancers in 1990
Int J Cancer
(1999)
P Pisani et al.
Estimates of the world-wide mortality from 25 cancers in 1990
Int J Cancer
(1999)
A Anttila et al.
Effect of organised screening on cervical cancer incidence and mortality in Finland 1963–1995Recent increase in cervical cancer incidence
Int J Cancer
(1999)
H zur Hausen
Papillomavirus infections—a major cause of human cancers
Biochim Biophys Acta
(1996)

M.H Schiffman et al.

Epidemiological evidence that human papillomavirus infection causes most cervical intraepithelial neoplasia

J Natl Cancer Inst

(1993)

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Évaluer l’intérêt des tests de détection des HPV à haut risque (HPV HR) dans le dépistage et le suivi après traitement des lésions cervicales intra épithéliales de haut grade (LIEHG).
Une revue systématique de la littérature de 2000 à 2019 a été réalisée incluant les mots clefs suivant : « human papilloma virus », « HPV testing », « cervical squamous intraepithelial lesion », « cervical cancer ».
De nombreuses études randomisées et méta-analyses récentes ont des résultats concordants en faveur d’une supériorité des tests HPV HR par rapport au frottis cervico utérin (FCU) dans le dépistage et le suivi post traitement des LIEHG. En dépistage, la sensibilité des tests HPV HR est de 63 % à 98 % alors que celle du FCU est seulement de 38 % à 65 % pour la détection des LIEHG+ (LIEHG et cancers invasifs). Un test HPV HR négatif est associé à moins de 5 % de risque de LIEHG+ à 6 ans. De plus, après exérèse d’une LIEHG, les tests HPV HR possèdent une sensibilité > 90 % et une spécificité > 80 % pour prédire l’échec de traitement. Un test HPV HR négatif après conisation est associé à un risque d’échec < 2 % (valeur prédictive négative de 98 %), et de 12 à 25 % s’il est positif.
Les tests HPV HR sont performants, permettant un dépistage précoce des LIEHG+, une identification des femmes à bas risque en cas de test négatif, et une prédiction du risque d’échec après traitement.
To evaluate the value of high-risk HPV (HR HPV) testing in screening and post-treatment follow-up of high-grade squamous intraepithelial cervical lesions (HSIL).
A systematic review of the literature from 2000 to 2019 was conducted including the following keywords: “human papilloma virus”, “HPV testing”, “cervical squamous intraepithelial lesion”, “cervical cancer”.
Numerous recent randomized studies and meta-analyzes have concordant results in favor of HR HPV superiority over cervical smear in the screening and post-treatment monitoring of HSIL. In screening, the sensitivity of the HR HPV tests is 63% to 98% whereas that of the cervical smear is only 38% to 65% for the detection of HSIL+ (HSIL and invasive cancers). A negative HR HPV test is associated with less than 5% risk of LIEHG + at 6 years. In addition, after removal of a LIEHG, HR HPV tests have a sensitivity > 90% and specificity > 80% to predict treatment failure. After surgicale exision, a negative HR HPV test is associated with a risk of failure < 2% (negative predictive value of 98%), and 12–25% if it is positive.
HR HPV tests are effective, allowing early detection of LIEHG+ identification of low-risk women in case of negative test, and a prediction of the risk of failure after treatment.
Observational versus ablative treatment of low-grade squamous intraepithelial lesions. A retrospective paired cohort study. January 2010 January 2014
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A nivel mundial, está claramente establecido el manejo excisional de las lesiones intraepiteliales de alto grado; en cambio, existen 2 tendencias en el manejo de la lesión intraepitelial de bajo grado: seguimiento sólo con observación y esperar la remisión de la lesión, lo cual está bien documentado versus el uso de tratamiento ablativo que algunos autores proponen. El propósito de nuestro estudio fue evaluar de forma retrospectiva los resultados de la Clínica de Colposcopía de la Maternidad del Hospital Santo Tomás, comparando las pacientes manejadas de forma expectante con aquellas manejadas mediante tratamientos ablativos. Después de evaluar 242 casos que cumplían los requisitos planteados en el protocolo, se pudo observar que no había diferencias estadísticamente significativas entre ambos grupos, en cuanto a remisión, progresión o persistencia de las lesiones a los 6 meses y a los 12 meses.
The indication for excisional management of high-grade intraepithelial lesions of the cervix is clearly established worldwide. However, low-grade lesions are managed in two different ways: follow-up with routine evaluation of the lesions, with expectation of complete remission, which is well documented in the literature, versus ablative treatment. The purpose of this study was to retrospectively evaluate the results of the Colposcopy Clinic of the Santo Tomás Hospital by comparing patients managed with follow-up and those receiving ablative treatment. After reviewing 242 clinical charts, we observed no statistically significant difference between the two groups in remission, progression or persistence of the lesions at 6 and 12 months.
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2015, Journal of Clinical Virology
Although it is hypothesised that human papillomavirus (HPV) testing may have a role in surveillance of patients conservatively treated for stage IA squamous cell cervical carcinoma, research on this topic has been minimal.
To determine: (1) the changes in HPV test result from treatment onward; (2) the time to viral clearance; and (3) the negative predictive value (NPV) and positive predictive value (PPV) of HPV test result for the detection of CIN2 or worse (CIN2+) during follow-up.
In a multicentre retrospective follow-up study of a consecutive series (1997–2009) of 91 patients, longitudinal outcome measures were estimated as cumulative probabilities using the Kaplan–Meier method.
For patients testing HPV-positive at the first follow-up visit (n = 44), the probability of change to negative rose from 0 to 0.78 between 7 and 21 months after treatment. For HPV-negative patients (n = 47), the probability of change to positive rose to 0.13 between 9 and 26 months. After a median follow-up of 50 months (range, 2–80), the NPV for CIN2+ was 1.00. The PPV was 0.60 (95% confidence interval, 0.43–0.77) after 26 months. The median time to detection was 5 months.
If adequately confirmed, these findings would indicate that HPV testing is capable to identify the patients who have had their lesions fully removed, and would make it possible to focus follow-up efforts on a subset of patients at high risk of residual or progressive disease.
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We investigated the role of high-risk human papillomavirus (hr-HPV) in patients with Barrett’s dysplasia and adenocarcinoma (EAC). Clearance vs persistence of HPV (DNA, E6 or E7 mRNA, and p16INK4A protein) and overexpression or mutation of p53 were determined for 40 patients who underwent endotherapy for Barrett’s dysplasia or EAC. After ablation, dysplasia or neoplasia was eradicated in 34 subjects (24 squamous, 10 intestinal metaplasia). Six patients had detectable lesions after treatment; 2 were positive for transcriptionally active hr-HPV, and 4 had overexpression of p53. Before endotherapy, 15 patients had biologically active hr-HPV, 13 cleared the infection with treatment, and dysplasia or EAC was eliminated from 12 patients. One patient who cleared HPV after ablation acquired a p53 mutation, and their cancer progressed. Of 13 patients with overexpression of p53 before treatment, 10 cleared the p53 abnormality after ablation with eradication of dysplasia or neoplasia, whereas 3 of 13 had persistent p53 mutation-associated dysplasia after endotherapy (P = .004). Immunohistochemical and sequence analyses of p53 produced concordant results for 36 of 40 samples (90%). Detection of dysplasia or neoplasia after treatment was associated with HPV persistence or continued p53 overexpression.
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^☆: This study was supported by Europe Against Cancer, the Swedish Cancer Society, the Swedish Society for Medical Research, and Anders Otto Swärd Foundation for Medical Research. The Swedish Medical Research Council supports JD.

¹: The authors thank Assistant Professor Peter Lidbrink, Department of Dermatovenereology, Huddinge University Hospital, for invaluable help with examining the male partners; Dr. Ilvars Silins for the statistical analyses; and Ms. Carina Eklund for excellent technical assistance.

^†: JMMW died February 1, 2000.

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Original researchRate of human papillomavirus clearance after treatment of cervical intraepithelial neoplasia 1 ☆,

Abstract

Section snippets

Materials and methods

Results

Discussion

Lancet

Am J Obstet Gynecol

Am J Obstet Gynecol

Gynecol Oncol

Gynecol Oncol

Obstet Gynecol

Estimates of the worldwide incidence of 25 major cancers in 1990

Int J Cancer

Estimates of the world-wide mortality from 25 cancers in 1990

Int J Cancer

Effect of organised screening on cervical cancer incidence and mortality in Finland 1963–1995Recent increase in cervical cancer incidence

Int J Cancer

Papillomavirus infections—a major cause of human cancers

Biochim Biophys Acta

Epidemiological evidence that human papillomavirus infection causes most cervical intraepithelial neoplasia

J Natl Cancer Inst

Original research
Rate of human papillomavirus clearance after treatment of cervical intraepithelial neoplasia ¹ ☆,