Colposcopic Regression Patterns in High-Grade Cervical Intraepithelial Neoplasia

Brewer, Cheryl A.; Wilczynski, S P; Kurasoaki, T; Daood, R; Berman, Michael L.

doi:10.1097/00128360-199804000-00018

Cited by 5 publications

(7 citation statements)

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“…2). Such a strategy for defining partial response has been utilized in other clinical trials involving cervical dysplasia [26,27]. Stable disease (SD) was defined as persistent CIN III with less than 50% reduction of lesion size.…”

Section: Response Evaluationmentioning

confidence: 99%

Heat shock fusion protein-based immunotherapy for treatment of cervical intraepithelial neoplasia III

Einstein

Kadish

Burk

et al. 2007

Gynecologic Oncology

129

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Objectives-SGN-00101 (HspE7, Nventa, San Diego, CA) is a novel therapeutic vaccine consisting of a fusion protein containing an M. bovis BCG heat shock protein (Hsp65) covalently linked to the entire sequence of HPV 16 E7. This trial was designed to evaluate the efficacy and toxicities of HspE7 in women with CIN III.Methods-HIV (−) women with biopsy-proven CIN III were eligible. Two cohorts were accrued; one cohort to establish efficacy and a second cohort with a longer follow-up period to improve the precision of the trial to estimate response rates. Each patient underwent 3 monthly subcutaneous vaccinations with 500 µg of HspE7 followed by monthly colposcopic follow-up for 1 month in cohort 1 and an extended observation period (2 months) in cohort 2. All patients then underwent a LEEP or cone biopsy of the cervix. A complete pathologic response (pCR) was defined as no evidence of CIN or CIN I (only HPV changes). A partial response (PR) was defined as colposcopic lesion regression of >50% in size. Cervicovaginal lavage samples were obtained at each visit for HPV typing using MY09/ MY11 HPV PCR.Results-Seventy-two patients were registered and screened, of whom 64 were eligible. Fifty-eight patients completed the trial and were evaluable (31 in cohort 1, 27 in cohort 2). There were no significant epidemiologic or HPV type differences between the 2 cohorts so responses were combined for analysis. Of the 58 evaluable patients, 13 (22.5%) had a pCR; 32 (55%) had a PR and 11 (19%) had stable disease. Two (3.5%) patients in cohort 2 had microinvasive disease and were defined as progressive disease. Thirty-three of 58 (57%) of the patients were infected with HPV 16 prior to vaccination or in subsequent visits. There was no significant difference in regression in women infected with HPV 16 compared to those without HPV 16 infection (88% vs. 70%; p=0.12). Women who had a previous LEEP or ablation for CIN were 2.7 times more likely to have a complete response compared to patients without previous treatment, although the difference was not statistically significant (95% CI for rate ratio: 0. 95-6.19, p=0.10). At a cellular level, there was a significant association between local inflammation and response; lower grade of lesional inflammation correlated with a response to HspE7 (p=0.04 using Wilcoxon rank sum test). Conclusions-HspE7 appeared to demonstrate activity in women with CIN III and met a priori assumptions for efficacy; however, it is unclear whether this response was due to natural regression rather than treatment effect. HspE7, which targets the HPV 16 E7 oncoprotein, had efficacy in patients infected with HPV types other than 16, suggesting cross-reactivity. A larger randomized, controlled trial is needed to better define efficacy and to identify subsets of women most likely to benefit from immunotherapy.

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Section: Response Evaluationmentioning

confidence: 99%

Heat shock fusion protein-based immunotherapy for treatment of cervical intraepithelial neoplasia III

Einstein

Kadish

Burk

et al. 2007

Gynecologic Oncology

129

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“…A pathologic complete response (CRpath) was defined as a post-vaccine LEEP specimen negative for CIN. A partial response (PR) was defined as a 50% or more reduction of lesion size post-vaccination based on quantitative colposcopic measurements made on grid colposcopy forms [18, 19]. Stable disease (SD) was defined as persistent CIN III with less than 50% reduction of lesion size.…”

Section: Methodsmentioning

confidence: 99%

Serological response to an HPV16 E7 based therapeutic vaccine in women with high-grade cervical dysplasia

Doorslaer

Reimers

Studentsov

et al. 2010

Gynecologic Oncology

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Purpose-Infection with oncogenic human papillomaviruses has been linked to the development of cervical neoplasia and cancer. The exclusive expression of E7, a viral oncogene, in infected cells makes this protein an ideal target for immunotherapy. We recently reported on the results of a trial in women with cervical carcinoma-in-situ using HspE7, a protein vaccine consisting of full length HPV16 E7 linked to a heat shock protein from M. bovis. The stimulating effects of HspE7 on specific cytotoxic T lymphocytes have been demonstrated in vitro and in (pre-)clinical trials. The induction of a B-cell response by HspE7 and its association with clinical outcome is unknown, and is the purpose of this study.Experimental design-We measured the serum IgG levels against HPV16 E7 and HPV16 and -18 VLPs using a multiplexed Luminex based assay in 57 women with CIS who received the HspE7 vaccine.Results-Vaccination with HspE7 results in a modest, yet maintained increase in HPV16 E7 specific IgG levels. While not significant, increased HPV16 E7 IgG levels appear to be correlated with a positive therapeutic effect. Women who were previously treated for recurrent disease (by LEEP) had significantly higher HPV16 E7 IgG levels compared with subjects without recurrent disease (p=0.01). In women with recurrent disease, higher IgG levels correlated with complete pathological response. Conflict of Interest StatementMHE has advised Nventa, the company producing HspE7, but does not receive an honorarium. The other authors have no conflict of interest to disclose.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Conclusions-This study suggests that IgG levels could potentially be used as a marker for response to a therapeutic vaccine. Further translational investigations of the 'priming' of local immune responses using extirpative procedures should be explored. NIH Public Access

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“…A large series examining the medical treatment of CIN using retinoic acid showed statistically significant differences between the regression rates in treated and placebo groups with CIN 2 but not with CIN 3 19 . CIN 2 was also found to be more likely that CIN 3 to regress in a small group of patients treated with β carotene 20 . Although the numbers of studies comparing the regression rates of women with CIN 2 and CIN 3 treated medically are small and even contradictory, 21 it appears that distinguishing women with CIN 2 may identify a subgroup who will respond differently from those with CIN 3, providing these patients with an opportunity to benefit from other than conventional ablative or excisional therapy 19 .…”

Section: How Should We Grade Cin?mentioning

confidence: 99%

How should we grade CIN?

Heatley

2002

Histopathology

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How should we grade CIN? The grading of cervical intraepithelial neoplasia (CIN) is problematic. CIN represents a morphological continuum, but biopsies displaying this lesion are classified into two (e.g. Bethesda) or three grade categories, sometimes with poor reproducibility. There are also difficulties in reliably distinguishing low-grade CIN from its reactive simulants. Because of problems with inter- and intra-observer disagreement in the grading of CIN and the diagnosis of low-grade lesions, three expert contributions were commissioned to address the question 'how should we grade CIN?'.

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Colposcopic Regression Patterns in High-Grade Cervical Intraepithelial Neoplasia

Cited by 5 publications

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Heat shock fusion protein-based immunotherapy for treatment of cervical intraepithelial neoplasia III

Heat shock fusion protein-based immunotherapy for treatment of cervical intraepithelial neoplasia III

Serological response to an HPV16 E7 based therapeutic vaccine in women with high-grade cervical dysplasia

How should we grade CIN?

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