(1) Mehlhorn G, et al. 2014, HPV16-L1-specific Antibody Response Is Associated with Clinical Remission of High-risk HPV-positive Early Dysplastic Lesions.

Anticancer Research 34: 5127-5132
The paper shows that HPV-specific immune competence as evidenced by the detection of HPV16-L1-specific antibodies strongly correlates with clinical remission
of early dysplastic lesions. The risk of progression to CIN3 for L1 antigen and HPV16-L1 antibody double-positive
women is extremely low (about 6%) and very rarely (in 8.7%) associated with CIN during follow-up.


(2)  S.-J. Lee, A.-W. Lee, C.-S. Kang, J.-S. Park, D.-C. Park, E.-Y. Ki, K.-H. Lee, J.-H. Yoon, S.-Y. Hur, T.-J. Kim, 2014, Clinicopathological Implications of Human Papilloma Virus (HPV) L1 Capsid Protein Immunoreactivity in HPV16 – Positive Cervical Cytology. International Journal of Medical Sciences, 11(1):80-86. Doi: 10.7150/ijms.5585

Our study demonstrates that the expression of HPV L1 is low in advanced dysplasia. Furthermore, the absence of HPV L1 in HPV16-positive low-grade cytology (i.e., ASCUS and LSIL) is strongly associated with high-grade histopathology diagnoses. The multiplicity of HPV infections may have an important role in high-grade histopathology diagnoses (≥CIN3) in HPV L1-positive cases.


(3) Mehlhorn G, et al. 2013, HPV L1 detection discriminates cervical precancer from transient HPV infection: a prospective international multicenter study. Nature-Modern Pathology, 26, 967-974

The prospective international multicenter study include 908 non-therapy relevant HPV high risk positive mild to moderate dysplasia (LSIL and HSIL) with a follow-up of the patients up to 54 months. The results of all former studies were confirmed and strengthened. Only about 20% of all L1 positive cases show a progression to the histological evaluated CIN3 lesions, contrary to L1 negative cases which show a progression in 84%. The data of the study with Cytoactiv allowed a clear distinction between transient HPV high-risk infections and progressive precancerous lesions.


(4) S. W. Byun, A. Lee, S. Kim, Y. J, Choi, Y. S. Lee, J. S. Park, 2013, Immunostaining of p16INK4a /Ki-67 and L1 Capsid Protein on Liquid-based Cytology Specimens Obtained from ASC-H and LSIL-H Cases, International Journal of Medical Sciences

This study analyzed the expression of p16INK4a/Ki-67 and L1 capsed protein and conducted HPV DNA typing in liquid-based cytology specimens (LBCS) of ASC-H and LSIL-H patients to develop a more effective set of surrogate markers for the prediction of high-risk precursor or invasive cervical lesions.


(5) R. Hilfrich PhD, 2013, HPV L1 Detection as a Prognostic Marker for Management of HPV High Risk Positive Abnormal Pap Smears, Book InTech – Human Papillomavirus and related diseases; from bench to bedside – a diagnostic and preventive perspective

The article within the book summarizes the scientific dates for the management of abnormal Pap smears with the prognostic marker Cytoactiv.


(6) Gerd Böhmer, Thomas Weyerstahl, 2011, Management of abnormal results of the Cervix Uteri during cervical cancer screening, Thieme Gynaecology up2date

This review article summarizes the state of the art recommendations for the management of abnormal Pap smears. Especially Cytoactiv as PROGNOSTIC MARKER, is distinguished from Biomarkers, like CinTectPlus


(7) S.J. Lee et al. 2011, Correlation between immunocytochemistry of human papilloma virus L1 capsid protein and behavior of low-grade cervical cytology in Korean women, Journal of Obstetrics and Gynaecology Research

The prospective trial of 318 women confirmed the benefit for Cytoactiv for the management of HPV high risk positiv LSIL women. The positive predictive value of HPV L1-positive cases for no progression was 91.7%, and the negative predictive value of HPV L1-negative cases for progression to high-grade lesions was 27.7


(8) M.T. Galgano et al. 2010, Using Biomarkers as Objective Standards in the Diagnosis of Cervical Biopsies, Am J Surg Pathol.

This diagnostic paper confirms the superior high specificity of 96,7% for Cytoactiv in contrast to p16 and ki67. In addition the relative reproducibility of the adjunctive stains as raw agreement was highest for Cytoactiv (96,9% and 0,88 Kappa) follwoed by p16INK4a (76.5%, 0.64) and ki67 (73.6%, 0.55)


(9) Y.S. Choi et al, 2010, Human Papillomavirus L1 Capsid Protein and Human Papillomavirus Type 16 as Prognostic Markers in Cervical Intraepithelial Neoplasia 1, Int Jour of Gynecol Cancer

The first Korean study with 101 HPV High risk positive CIN1 confirms that the HPV L1 protein expression is closely related to spontaneous disease regression.


(10) Griesser H, Sander H, Walczak C, Hilfrich R. 2009.HPV vaccine protein L1 predicts disease outcome of high-risk HPV+ early dysplastic lesions. Am J Clin Pathol

The prospective study included 211 non-therapy relevant, HPV HR-positive mild to moderate dysplasia (LSIL and HSIL) with a follow-up of the patients between 36 – 48 months. The results of all former retrospective studies were confirmed and strengthened. Depending on patients age (<30 / >30) and the classification of the precancerous lesion (LSIL or HSIL) only 20 % of all L1 positive cases showed a progression. The progression rate of the L1 negative cases was very high: 97%!


(11) Scheidemantel et al. 2008, Expression pattern of HPV L1 capsid protein in PAP tests: a potential biomarker in risk assessment for high grade SIL lesion. Abstract Ann. M. Am. Soc. of Cytopathology

The first US study using ThinPrep slides on 111 HR-HPV positive cases shows that NONE of the cytoactiv positive patients showed a progression towards cervical cancer. All progredient cases were found to be L1 negative.


(12) Negri G et al. 2008, p16 andHPV immunohistochemistry is helpful for estimating the behaviour of low grade dysplastic lesions of the cervix uteri. AmJ SurgPathol

The study confirms the use of cytoactiv as prognostic marker with regards to prediction of the outcome of a mild/moderate dysplasia. Additionally they show good value of combining L1 protein detection with p16 and HPV high risk test.


(13) Hilfrich R, Hariri J, 2008. Prognostic relevance of HPV L1 capsid protein detection within mild to moderate dysplastic lesions of the cervix uteri in combination with a second biomarker p16. Anal Quant Cytol Histl

The Danish study with 191 punch biopsies (CIN I/II) showed equal results for the L1 capsid protein detection using histological specimen. Progression of the precancerous lesions was found in 83,9% of the L1 negative cases and was 27,5% in L1 positive cases (p-values <0.001). Compared to p16 only the L1 capsid protein detection proved prognostic value at this early level. The specificity of Cytoactiv is 100%.


(14) Rauber D et al. 2008. Prognostic significance of the detection of the human papillomavirus L1 protein in smears of mild to moderate cervical intraepithelial lesions. Eur J Obstet Gyn Reprod Biol

This retrospective study with 279 HR-positive mild and moderate dysplasias (LSIL / HSIL) confirmed the previous findings. The progression rate of L1 capsid protein positive cases was found to be only 12,3% (p-value <0,001).

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