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1.
Heath S Willis V Allan K Purdie K Harwood C Shields P Simcock R Williams T Gilbert DC 《Clinical oncology (Royal College of Radiologists (Great Britain))》2012,24(1):e18-e23
Aims
The association between squamous cell carcinoma of the head and neck (HNSCC) and infection with human papilloma viruses (HPV) has created considerable interest. Rates of primary oropharyngeal cancers have shown increasing incidence and declining age at presentation over the last decade, believed to relate to infection with oncogenic or high-risk subtypes of HPV (HR-HPV). HR-HPV-associated tumours have reportedly improved outcomes when compared with HPV-negative cancers. Within the UK, rates of HR-HPV in HNSCC have not yet been reported.Materials and methods
We analysed consecutive retrospective cases of oropharyngeal cancer presenting between 2004 and 2007.Results
Thirty-seven per cent of 83 oropharyngeal tumours stained positively for p16INK4A, a marker of HPV infection (73% tonsillar cancers being p16 INK4A positive, 30% tongue and 43% floor of mouth tumours). HPV16 DNA was demonstrated in 75% p16 INK4A cases. Despite being more advanced with higher T-stage and nodal burden at presentation, HR-HPV-associated HNSCC showed significantly improved rates of disease-free and overall survival, in particular with improved rates of response to radical radiotherapy.Conclusion
HPV16 infection seems to be a clinically significant cause of oropharyngeal HNSCC in the UK and the collection of national data should be supported. 相似文献2.
Francesco Broccolo Giulia Ciccarese Agostino Rossi Luca Anselmi Francesco Drago Antonio Toniolo 《Infectious agents and cancer》2018,13(1):32
Background
Oral and oropharyngeal squamous cell carcinomas (OSCC and OPSCC) represent the majority of head and neck squamous cell carcinomas (HNSCC). Human papillomavirus (HPV) is an important etiologic factor together with Epstein-Barr virus (EBV). Little is known on the prevalence of major herpesviruses [EBV, cytomegalovirus (CMV) and HHV-6, ??7 and???8] in HNSCCs.Methods
Fifty-one formalin-fixed paraffin-embedded (FFPE) tissue samples taken at surgery (40 oropharyngeal, 11 oral) were analyzed for 40 HPV genotypes (20 high-risk types), EBV, CMV, HHV-6, ??7 and???8 by quantitative PCR. Expression of the HPV-induced p16INK4A protein was also investigated by immunohistochemistry (IHC).Results
In SCC, the prevalence of EBV was significantly higher compared to that of HPV (EBV 51% vs. HPV 19.5%; P =?0.005). HPV infection was found in 25% of OPSCC and in none of the OSCC; conversely, higher prevalence of EBV was found in OSCC (72.7%). HPV and EBV co-infection was detected only in 4 (10%) OPSCC. CMV was detected in only two cases, whereas HHV-6, ??7 and???8 resulted negative. The prevalence of HPV but no EBV was associated with the non-keratinizing SCC type (NKSCC) compared to the keratinizing SCC type (KSCC)(HPV-DNA P <?0.005; EBV?=?0.054).Conclusions
Single HPV or EBV positivity was higher in OSCC than in OPSCC. Other potentially oncogenic herpesvirus types were minimally or not represented.3.
K Hellman D Lindquist C Ranhem E Wilander S Andersson 《British journal of cancer》2014,110(6):1561-1570
Background:
This study aimed to determine human papillomavirus (HPV) status and to investigate p16INK4A and Ki-67 expression and their correlation with clinical parameters and survival in women with primary carcinoma of the vagina (PCV).Methods:
The presence of HPV DNA was evaluated by PCR. Genotyping was performed by Luminex in 68 short-term (⩽2 years) and long-term (⩾8 years) PCV survivors. p16INK4A and Ki-67 expression was evaluated by immunohistochemistry.Results:
Human papillomavirus DNA was detected in 43% of patients, the majority (63%) of whom were HPV16 positive. High p16INK4A expression was significantly correlated with low histopathological grade (P=0.004), HPV positivity (P=0.032), and long-term survival (P=0.045). High Ki-67 expression was negatively correlated with histopathological grade (P<0.001) and tumour size (P=0.047). There was an association between HPV positivity and low histopathological grade, but not between HPV positivity and survival.Conclusion:
High p16INK4A expression was associated with long-term survival, but the only independent predictors for survival were tumour size and histopathological grade. Our results indicate that p16INK4A and Ki-67 expression might be useful in tumour grading, and that it might be possible to use p16INK4A expression as a marker for HPV positivity, but this has to be further elucidated. 相似文献4.
Megan Q. Zhang MD Samir K. El‐Mofty DMD PhD Rosa M. Dávila MD 《Cancer cytopathology》2008,114(2):118-123
BACKGROUND
Fine‐needle aspiration (FNA) biopsy often is the first diagnostic procedure performed in patients with head and neck masses. When squamous cell carcinoma (SCC) is diagnosed, proper management and improved prognosis depends on identification of the primary tumor. Recent studies have indicated that human papillomavirus (HPV) infection is associated closely with oropharyngeal SCC and that these tumors have a distinct nonkeratinizing morphology. In this study, the authors explored the value of identifying HPV‐related tumors in neck metastases to determine the origin of occult primary head and neck squamous cell carcinoma (HNSCC).METHODS
Thirty FNA biopsies of neck metastases from patients with HNSCC were recovered from the authors' files from 2004 to 2005. The primary sites included 13 oropharynx, 13 oral cavity, and 4 larynx/hypopharynx. All patients had corresponding tissue samples from the neck mass and the primary carcinoma. The FNA specimens and corresponding tissue samples were classified as either nonkeratinizing SCC (NKSCC) or keratinizing SCC (KSCC). In situ hybridization for HPV (HPV‐ISH) was performed using ethanol‐fixed, Papanicolaou‐stained smears. A positive signal was defined as dark blue or black nuclear dots. Corresponding formalin‐fixed, paraffin‐embedded tissue sections also were processed for HPV‐ISH.RESULTS
Twenty of the 30 FNA specimens were KSCC, and 10 were NKSCC. Eight of the 10 NKSCCs originated in the oropharynx, and 2 had nonoropharyngeal origin. HPV was detected in 7 of 10 NKSCCs. Ten of 30 (33%) FNA biopsies were positive for HPV, and 9 of those biopsies were metastatic from the oropharynx. Nonkeratinzing morphology or HPV‐positive ISH in FNA samples significantly predicted oropharyngeal origin (P < .0069 and P < .0004, respectively).CONCLUSIONS
NKSCC in metastatic cervical lymph nodes predicted positive HPV‐ISH and was strongly suggestive of an oropharyngeal primary tumor. Cancer (Cancer Cytopathol) 2008. © 2008 American Cancer Society. 相似文献5.
Hina Sarwath Devendra Bansal Nazik Elmalaika Husain Mahmoud Mohamed Ali A. Sultan Shahinaz Bedri 《Infectious agents and cancer》2017,12(1):50
Background
Cervical cancer is the fourth most common cancer in women worldwide with highest incidence reported in Eastern Africa in 2012. The primary goal of this study was to study the expression of p16INK4a in squamous cell carcinoma (SCC) of the cervix by immunohistochemistry (IHC) and determine relation with clinico-pathological parameters. This study further explored the correlation of p16INK4a immunostaining with another proliferation marker, Ki-67 and to study if human papillomavirus (HPV) IHC can be used as a marker for detection of virus in high-grade dysplasia.Methods
A total of 90 samples, diagnosed for cervical cancer, were included in the study. Fixed Paraffin Embedded (FFPE) tissue sections were stained with anti-p16INK4a, anti-Ki-67 and anti-HPV antibodies using automated immunohistochemistry platform (ASLink 48-DAKO).Results
Immunohistochemical protein expression of p16INK4a positivity was found to be highest in SCC (92.2%, n = 71) than other HPV tumors (76.9%, n = 10). The majority of cases (97.4%) were p16INK4a positive in the age group 41–60 years. In addition, a statistically significant difference between p16INK4a and HPV was observed among total cervical tumor cases and SCC cases.Conclusions
As expected staining of invasive cervical cancer with anti-HPV showed rare positivity because HPV heralds active infection in dysplastic lesions and not of frank cervical carcinoma. In contrast, anti-p16INK4a IHC results showed positive correlation in SCC and other cervical tumors.6.
Vanessa Deschoolmeester Veerle Van Marck Marc Baay Christine Weyn Peter Vermeulen Eric Van Marck Filip Lardon Veronique Fontaine Jan B Vermorken 《BMC cancer》2010,10(1):117
Background
Based on the well-recognized etiological role of human papillomavirus (HPV) in cervical, anogenital and oropharyngeal carcinogenesis, a potential role of HPV in colorectal carcinogenesis has been suggested. For that reason, the aim of the present study was to investigate the presence of HPV DNA in colorectal carcinomas (CRC) and to study overexpression of p16INK4A as a marker for the presence of an active HPV oncoprotein E7. These findings were correlated with clinical and pathological prognostic factors of CRC. 相似文献7.
Human papillomavirus (HPV)‐associated oropharyngeal squamous cell carcinomas (OPSCCs) frequently show different clinical and pathological features, which tend to be younger age, better performance status, less tobacco and alcohol consumption, more poorly differentiated histopathology, but usually with better treatment response and prognosis compared with HPV‐negative OPSCCs. In tumor tissue, HPV infection is closely correlated with p16INK4A expression, which has been suggested to be a surrogate biomarker of HPV infection. However, there is diversity of sensitivity and specificity about p16INK4A in surrogate detection of HPV status. Herein, we summarize the current knowledge and note some aspects for consideration concerning p16INK4A as a surrogate biomarker for HPV‐associated OPSCC. 相似文献
8.
Jureeporn Chuerduangphui Chamsai Pientong Piyawut Swangphon Sanguanchoke Luanratanakorn Ussanee Sangkomkamhang Thumwadee Tungsiriwattana Pilaiwan Kleebkaow Ati Burassakarn Tipaya Ekalaksananan 《Medical oncology (Northwood, London, England)》2018,35(6):93
Human papillomavirus (HPV) E2 and L1 proteins are expressed in cervical cells during the lytic stage of infection. Overexpression of p16INK4A is a biomarker of HPV-associated cervical neoplasia. This study investigated antibodies to HPV16 E2, HPV16 L1, and p16INK4A in sera from women with no squamous intraepithelial lesion (No-SIL) of the cervix, low-grade SIL, high-grade SIL, and cervical squamous cell carcinoma (SCC). HPV DNA was detected by polymerase chain reaction. Anti-E2, -L1, and -p16INK4A antibodies in sera were determined by western blot. Among 116 samples, 69 (60%) were HPV DNA-positive. Percentages seropositive for anti-E2, -L1, and -p16INK4A antibodies were 39.6, 22.4, and 23.3%, respectively. Anti-E2 antibody was significantly correlated with HPV DNA-positive cases. Eighty-seven women (75%) were regarded as infected with HPV, having at least one positive result from HPV DNA, L1, or E2 antibody. Antibody to p16INK4A was associated with HPV infection (odds?=?5.444, 95% CI 1.203–24.629, P?=?0.028) and precancerous cervical lesions (odds?=?5.132, 95% CI 1.604–16.415, P?=?0.006). Interestingly, the concurrent detection of anti-E2 and -p16INK4A antibodies was significantly associated with HPV infection (odds?=?1.382, 95% CI 1.228–1.555, P?=?0.044). These antibodies might be good candidate biomarkers for monitoring HPV-associated cervical lesion development to cancer. 相似文献
9.
p16INK4a/Ki‐67 co‐expression specifically identifies transformed cells in the head and neck region
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Csaba Toth Gerhard Dyckhoff Steffen Wagner Franziska Müller Claus Wittekindt Kolja Freier Peter Plinkert Jürgen Hoffmann Svetlana Vinokurova Jens Peter Klussmann Magnus von Knebel Doeberitz Miriam Reuschenbach 《International journal of cancer. Journal international du cancer》2015,136(7):1589-1599
p16INK4a immunohistochemical overexpression is an overall reliable surrogate marker of human papillomavirus (HPV)‐associated head and neck squamous cell carcinomas (HNSCC). However, cases of ambiguous p16INK4a overexpression are regularly detected in the head and neck: p16INK4a expression can be observed in non‐malignant tissue, such as tonsillar crypt epithelium and a proportion of branchial cleft cysts. Additionally, diverse patterns of p16INK4 expression can complicate interpretation of “p16INK4a‐positivity”. These aspects impede the unrestricted application of p16INK4a as a diagnostic marker in the head and neck. We hypothesized that combined detection of p16INK4a and the proliferation marker Ki‐67 could support clarification of ambiguous p16INK4a expression in the head and neck by specifically indicating p16INK4a‐expressing cells with proliferative activity. p16INK4a/Ki‐67 co‐expression in a combined staining procedure was correlated to distinct p16INK4a expression patterns and HPV status (HPV DNA followed by E6*I oncogene mRNA detection) in 147 HNSCC and 50 non‐malignant head and neck samples. p16INK4a/Ki‐67 co‐expression only occurred in transformed cells of the head and neck. Co‐expression was never detected in non‐transformed cells. Combined p16INK4a/Ki‐67 expression was stringently associated with a diffuse p16INK4a expression pattern. All HPV oncogene‐expressing HNSCC showed p16INK4a/Ki‐67 co‐expression. We demonstrate that p16INK4a/Ki‐67 co‐expression occurs exclusively in transformed cells of the head and neck. Our findings indicate a substantial impact of combined p16INK4a/Ki‐67 expression in the assessment of ambiguous p16INK4a expression in the head and neck by specifically identifying p16INK4a‐expressing cells with proliferative activity. This property will be of considerable significance for head and neck histo‐ and cytopathology. 相似文献
10.
Duncan C Gilbert Anthony Williams Kimberley Allan Joanna Stokoe Tim Jackson Suzanne Linsdall Charles MH Bailey Jeff Summers 《Radiotherapy and oncology》2013
Background and Purpose
Squamous cell carcinomas of the anal canal are associated with infection with Human Papilloma Viruses (HPVs). Chemo-radiotherapy (CRT) gives 70% 3-year relapse-free survival. Improved predictive markers and therapeutic options are required.Methods
Tumours from 153 patients treated with radical chemo-radiotherapy (50.4 Gy in 28# with concurrent Mitomycin and 5-Fluorouracil between 2004 and 2009) were retrieved and immunohistochemistry performed for p16INK4A, p53 and EGFR and correlated with outcome. Primary and relapsed samples were analysed for mutations in KRAS.Results
137/153 (89.5%) stained moderately or strongly for p16INK4A. p16INK4A correlated strongly with outcome. 37/137 patients demonstrating moderate/strong p16INK4A expression relapsed (27.0%), as opposed to 10/16 (62.5%) with absent/weak staining (log rank test p < 0.001). p16 and p53 expression were inversely correlated. p16INK4A negative tumours were more frequent in men. p16INK4A negative patients had significantly worse overall survival (p < 0.001). No mutations in KRAS were identified in primary tumours or relapses following treatment.Conclusions
p16INK4A is strongly associated with relapse in SCC of the anus and identifies patients with very poor rates of relapse-free and overall survival. Primary and recurrent anal cancer expresses wild type KRAS, unaffected by treatment, supporting trials targeting EGFR in poor risk/recurrent anal cancer. 相似文献11.
P16INK4A immunostaining is a strong indicator for high‐risk‐HPV‐associated oropharyngeal carcinomas and dysplasias,but is unreliable to predict low‐risk‐HPV‐infection in head and neck papillomas and laryngeal dysplasias
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Jeroen J. Mooren Sibel E. Gültekin Jos M.J.A.A. Straetmans Annick Haesevoets Carine J. Peutz‐Kootstra Christian U. Huebbers Hans P. Dienes Ulrike Wieland Frans C.S. Ramaekers Bernd Kremer Jens P. Klussmann 《International journal of cancer. Journal international du cancer》2014,134(9):2108-2117
Human papillomavirus (HPV) is a risk factor for the development of benign and malignant mucosal head and neck lesions. P16INK4A is often used as a surrogate marker for HPV‐infection, although there is still controversy with respect its reliability. Our aim was to determine if p16INK4A overexpression can accurately predict both high‐risk and low‐risk‐HPV‐presence in (pre)malignant and benign head and neck lesions. P16INK4A immunohistochemistry was performed on paraffin‐embedded tissue sections of 162 oropharyngeal squamous cell carcinomas (OPSCC), 14 tonsillar and 23 laryngeal dysplasias, and 20 tonsillar and 27 laryngeal papillomas. PCR, enzyme‐immunoassay and FISH analysis were used to assess HPV‐presence and type. Of the 162 OPSCC and 14 tonsillar dysplasias, 51 (31%) and 10 (71%) were HPV16‐positive, respectively. All tonsillar papillomas were HPV‐negative and four laryngeal dysplasias and 26 laryngeal papillomas were positive for HPV6 or ?11. P16INK4A immunohistochemistry revealed a strong nuclear and cytoplasmic staining in 50 out of 51 HPV16‐positive and 5 out of 111 HPV‐negative OPSCC (p < 0.0001) and in all HPV16‐positive tonsillar dysplasias, whereas highly variable staining patterns were detected in the papillomas and laryngeal dysplasias, irrespective of the HPV‐status. In addition, the latter lesions generally showed a higher nuclear than cytoplasmic p16INK4A immunostaining intensity. In conclusion, our data show that strong nuclear and cytoplasmic p16INK4A overexpression is a reliable surrogate indicator for HPV16 in OPSCC and (adjacent) dysplasias. For HPV6 or ?11‐positive and HPV‐negative benign and premalignant lesions of the tonsil and larynx, however, p16INK4A immunostaining is highly variable and cannot be recommended to predict HPV‐presence. 相似文献
12.
Reuschenbach M Tran T Faulstich F Hartschuh W Vinokurova S Kloor M Krautkrämer E Zeier M von Knebel Doeberitz M Sommerer C 《British journal of cancer》2011,104(8):1334-1341
Background:
High-risk human papillomaviruses (HR-HPVs) can be detected in a proportion of non-melanoma skin cancers. Data on prevalence are inconclusive, but are essential to estimate the relevance of HR-HPV, particularly with regard to prophylactic HPV vaccines for skin cancer prevention.Methods:
High-risk human papillomavirus DNA was investigated in 140 non-melanoma skin lesions from 54 immunocompetent patients and 33 immunosuppressed renal allograft recipients. Expression of p16INK4a, a marker for HR-HPV oncogene expression in the uterine cervix, and of p53 and pRB was evaluated immunohistochemically.Results:
The highest prevalence of HR-HPV was found in squamous cell cancer (SCC) (46.2% (6 out of 13) in immunosuppressed and 23.5% (4 out of 17) in immunocompetent patients). High-risk human papillomavirus positivity was accompanied by diffuse p16INK4a expression in most SCC (P<0.001) and basal cell cancers (P=0.02), while almost all SCC in situ were p16INK4a positive irrespective of HR-HPV presence (P=0.66). Diffuse p16INK4a expression was associated with lack of pRB expression (P=0.001). p53 was strongly expressed in 40.0% (56 out of 140) of the lesions irrespective of HR-HPV presence.Conclusion:
High-risk human papillomavirus can be detected in lesions of keratinised squamous epithelia. The association of HR-HPV with diffuse p16INK4a expression might indicate HR-HPV oncogene expression in a proportion of lesions. Overexpression of p53 suggests p53 pathway alterations in HR-HPV-positive and -negative lesions. 相似文献13.
Background
The pathogenic role of beta-HPVs in non melanoma skin cancer (NMSC), is not still completely understood, and literature data indicate that they might be at least cofactors in the development of certain cutaneous squamous cell carcinomas. However, only few reports contain data on basal cell carcinoma (BCC). The HPVs interact with many cellular proteins altering their function or the expression levels, like the p16INK4a and Akt. Our study aimed to determine the presence of different beta -HPV types and the expression of p16INK4a and Akt in BCC, the commonest NMSC, in the normal appearing perilesional skin and in forehead swab of 37 immunocompetent patients.Methods
The expression of p16INK4a and Akt, by immunohistochemistry, and the HPV DNA, by nested PCR, were investigated in each sample.Results
No correspondence of HPV types between BCC and swab samples was found, whereas a correspondence between perilesional skin and BCC was ascertained in the 16,7% of the patients. In BCC, 16 different types of beta HPV were found and the most frequent types were HPV107 (15,4%), HPV100 (11,5%) and HPV15 (11,5%) all belonging to the beta HPV species 2. Immunohistochemistry detected significant p16INK4a expression in almost all tumor samples (94,3%) with the highest percentages (> 30%) of positive cells detected in 8 cases. A statistically significant (p = 0,012) increase of beta HPV presence was detected in p16INK4a strongly positive samples, in particular of species 2. pAkt expression was detected in all tumor samples with only 2 cases showing rare positive cells, whereas Akt2 expression was found in 14 out of 35 BCC (40%); in particular in HPV positive samples over-expressing p16INK4a.Conclusions
Our data show that p16INK4a and pAkt are over-expressed in BCC and that the high expression of p16INK4a and of Akt2 isoform is often associated with the presence of beta-HPV species 2 (i.e. HPV 15). The association of these viruses with the up-regulation of p16INK4a and Akt/PI3K pathway suggests that in a subtype of BCC these viruses may exert a role in the carcinogenesis or in other, still undefined, biological property of these tumors. If this particular type of BCC reflects a different biology it will remain undisclosed until further studies on a larger number of samples will be performed. 相似文献14.
Francesca Paolini Angelo Carbone Maria Benevolo Vitaliano Silipo Francesca Rollo Renato Covello Paolo Piemonte Pasquale Frascione Rodolfo Capizzi Caterina Catricalà Aldo Venuti 《Journal of experimental & clinical cancer research : CR》2011,30(1):108
Background
The pathogenic role of beta-HPVs in non melanoma skin cancer (NMSC), is not still completely understood, and literature data indicate that they might be at least cofactors in the development of certain cutaneous squamous cell carcinomas. However, only few reports contain data on basal cell carcinoma (BCC). The HPVs interact with many cellular proteins altering their function or the expression levels, like the p16INK4a and Akt. Our study aimed to determine the presence of different beta -HPV types and the expression of p16INK4a and Akt in BCC, the commonest NMSC, in the normal appearing perilesional skin and in forehead swab of 37 immunocompetent patients.Methods
The expression of p16INK4a and Akt, by immunohistochemistry, and the HPV DNA, by nested PCR, were investigated in each sample.Results
No correspondence of HPV types between BCC and swab samples was found, whereas a correspondence between perilesional skin and BCC was ascertained in the 16,7% of the patients. In BCC, 16 different types of beta HPV were found and the most frequent types were HPV107 (15,4%), HPV100 (11,5%) and HPV15 (11,5%) all belonging to the beta HPV species 2. Immunohistochemistry detected significant p16INK4a expression in almost all tumor samples (94,3%) with the highest percentages (> 30%) of positive cells detected in 8 cases. A statistically significant (p = 0,012) increase of beta HPV presence was detected in p16INK4a strongly positive samples, in particular of species 2. pAkt expression was detected in all tumor samples with only 2 cases showing rare positive cells, whereas Akt2 expression was found in 14 out of 35 BCC (40%); in particular in HPV positive samples over-expressing p16INK4a.Conclusions
Our data show that p16INK4a and pAkt are over-expressed in BCC and that the high expression of p16INK4a and of Akt2 isoform is often associated with the presence of beta-HPV species 2 (i.e. HPV 15). The association of these viruses with the up-regulation of p16INK4a and Akt/PI3K pathway suggests that in a subtype of BCC these viruses may exert a role in the carcinogenesis or in other, still undefined, biological property of these tumors. If this particular type of BCC reflects a different biology it will remain undisclosed until further studies on a larger number of samples will be performed. 相似文献15.
Sakiko Nishio Takuma Fujii Hiroshi Nishio Kaori Kameyama Miyuki Saito Takashi Iwata Kaneyuki Kubushiro Daisuke Aoki 《Journal Of Gynecologic Oncology》2013,24(3):215-221
Objective
In cervical intraepithelial neoplasia (CIN), p16INK4a immunohistochemistry has been reported to be a useful diagnostic biomarker. However, limited information is available about the association between the p16INK4a immunohistochemistry and the outcomes of CIN. Here, we report p16INK4a immunohistochemistry as an effective biomarker to predict the outcomes of CIN.Methods
p16INK4a immunohistochemistry was performed in patients with CIN from January 2000 to August 2009. Among these patients, we have performed a retrospective analysis of the medical records to evaluate the outcome of CIN 1-2 and performed statistical analysis to determine the correlation between p16INK4a expression and the outcomes. We also performed HPV genotyping and analyzed the relation between the infecting human papillomavirus (HPV) genotype and the outcomes.Results
A total of 244 patients, including 82 with CIN 1, 60 with CIN 2, and 102 with CIN 3, were examined. The rate of p16INK4a overexpression increased with increasing CIN grade, 20.7% for CIN 1, 80.0% for CIN 2, and 89.2% for CIN 3, with significant differences between CIN 1 and CIN 2-3 group. In the 131 CIN 1-2 patients, the progression rate was significantly higher for the patients showing p16INK4a overexpression than for those not showing p16INK4a overexpression (p=0.005); the regression rate was also found to be significantly lower for the patients showing p16INK4a overexpression (p=0.003). High-risk HPV genotypes were detected in 73 patients (73.7%). Both progression and regression rates were not significantly different between the high-risk HPV-positive and HPV-negative groups (p=0.401 and p=0.381, respectively).Conclusion
p16INK4a overexpression was correlated with the outcome of CIN 1-2, and p16INK4a is considered to be a superior biomarker for predicting the outcome of CIN 1-2 compared with HPV genotyping. 相似文献16.
p16INK4A immunohistochemical staining and predictive value for progression of cervical intraepithelial neoplasia grade 1: A prospective study in China
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Guang‐Dong Liao John W. Sellors Hai‐Kui Sun Xun Zhang Yan‐Ping Bao Jose Jeronimo Wen Chen Fang‐Hui Zhao Yan Song Zhi Cao Shao‐Kai Zhang Ming‐Rong Xi You‐Lin Qiao 《International journal of cancer. Journal international du cancer》2014,134(7):1715-1724
p16INK4A is strongly expressed in tissues diagnosed as cervical intraepithelial neoplasia (CIN) and cancer in women infected with human papillomavirus (HPV), but few prospective studies have evaluated p16INK4A as a marker for the risk of low‐grade CIN (CIN1) progression. We investigated the prevalence of p16INK4A immunostaining by CIN grade and whether overexpression of p16INK4A in CIN1 predicts future risk for high‐grade CIN in Chinese women. 6,557 Chinese women aged 30–49 years were screened from 2003 to 2005 using cytology and carcinogenic HPV test. Colposcopy was performed on women with any abnormal result. p16INK4A Immunostaining was performed on biopsies from all women with CIN1, as well as randomly selected women with normal or CIN grade 2 and worse (CIN2+) biopsies. Women with CIN1 were followed up without treatment. Colposcopy was performed on all untreated women at a 2‐year interval. The prevalence of p16INK4A staining was 2.7%, 42.7%, 75.5%, 79.6% and 100% among women with normal, CIN1, 2, 3 and cancer biopsies, respectively (p < 0.001). HPV positivity was strongly associated with p16INK4A staining [odds ratios (OR) = 12.8; 95% confidence intervals (CI): 5.2–31.6]. p16INK4A staining of CIN1 biopsies at baseline was associated with an increased risk of finding high‐grade CIN over 2 years of follow‐up (OR = 1.43; 95% CI: 0.52–3.91). The two‐year cumulative incidence of CIN2+ for p16INK4A positive women was higher at 10.71% than for p16INK4A negative women at 1.30% (crude RR = 8.25, 95% CI: 1.02–66.62). p16INK4A overexpression is strongly associated with grade of CIN and risk of progression to high‐grade CIN in women with low‐grade lesions. 相似文献
17.
Panduka Samarawardana MD Donna L. Dehn PhD Meenakshi Singh MD Douglas Franquemont MD Chesney Thompson MD Loretta Gaido MD Kathleen C. Torkko PhD Petra Homer MS Stephanie Burke BS Matthew A. Titmus BS Vipul Nayi BS Kenneth R. Shroyer MD PhD 《Cancer cytopathology》2010,118(3):146-156
BACKGROUND
The primary goal of this study was to compare the clinical performance of an optimized and rigorously controlled immunocytochemical (ICC) assay for p16INK4a to high‐risk (HR) human papillomavirus (HPV) detection by polymerase chain reaction (PCR) as diagnostic adjuncts for cytology specimens from colposcopy patients.METHODS:
The study included 403 cervical cytology specimens collected within 3 months of colposcopy. The colposcopic impression and cervical biopsy diagnosis served as the standards for correlation with cytological, p16INK4a, and HPV data. p16INK4a was evaluated using an immunoperoxidase‐based assay that was linear over 4 logs for the detection of HeLa‐spiked positive control cytology specimens, using a threshold for positive test results that was based on receiver operating characteristic curve analysis. HR‐HPV was detected by multiplex PCR using genotype‐specific primers.RESULTS:
In all combined diagnostic categories (negative for intraepithelial lesion and malignancy, atypical glandular cells, atypical squamous cells of undetermined significance, atypical squamous cells cannot exclude high‐grade squamous intraepithelial lesion, low‐grade squamous intraepithelial lesion, and high‐grade squamous intraepithelial lesion), the p16INK4a ICC and HR‐HPV assays, respectively, had sensitivity of 81.7% and 83.3% (P = .81) and specificity of 78.1% and 50.9% (P < .001) for the detection of underlying ≥grade 2 cervical intraepithelial neoplasia (CIN) lesions on biopsy. Furthermore, the positive predictive value of p16INK4a ICC was greater than that of HR‐HPV for patients with biopsies ≥CIN‐2 (41.2% and 24.2%, respectively, P = .001).CONCLUSIONS:
This p16INK4a immunocytochemical assay has superior specificity but similar sensitivity to HR‐HPV testing to predict underlying high‐grade dysplastic lesions in patients who are referred for colposcopy. The determination of the overall performance characteristics of p16INK4a immunocytochemistry, as an independent test or in combination with HPV testing in low‐risk screening populations, however, will require subsequent large‐scale prospective clinical trials. Cancer (Cancer Cytopathol) 2010. © 2010 American Cancer Society. 相似文献18.
19.
BACKGROUND:
Although previous studies have shown that p16INK4a and Ki‐67 are sensitive and specific markers for high‐grade lesions (≥CIN2) on cervical biopsies, limited information is available regarding the performance of a dual‐staining approach as a diagnostic adjunct in cervical cytology. We evaluated a dual p16INK4a/Ki‐67 immunocytochemistry (ICC) assay to determine its sensitivity and specificity versus that of high‐risk HPV (HR‐HPV) in a US‐based pilot cytology study.METHODS:
ThinPrep specimens from 122 cervical cytology specimens encompassing 23 negative (NILM), 20 ASC‐US, 22 LSIL, 17 ASCH, 22 HSIL, and 18 AGC cases were processed for multiplexed ICC staining using a CINtec Plus Kit. Dual‐positive assay results were defined based on the detection of 1 or more epithelial cells that were stained for both p16INK4a and Ki‐67 without regard to cellular morphology. HR‐HPV testing was performed by multiplex PCR with capillary electrophoresis genotyping.RESULTS:
Dual staining for p16INK4a and Ki‐67 was frequently detected in HSIL and AGC but was rarely detected in NILM cases. The HR‐HPV assay showed a sensitivity of 76.2% and a specificity of 55.8% for the detection of clinically significant cervical squamous or endometrial lesions. In contrast, the colocalization of p16INK4a plus Ki‐67 maintained a high sensitivity of 81.8% and improved specificity to 81.8% for biopsy‐confirmed CIN2/3, endocervical adenocarcinoma, or endometrial adenocarcinoma.CONCLUSIONS:
Dual staining for p16INK4a/Ki‐67 immunocytochemistry dramatically increased specificity and maintained high‐level sensitivity for the diagnosis of CIN2/3 or glandular lesions compared with PCR‐based testing for HR‐HPV. Cancer (Cancer Cytopathol) 2012. © 2011 American Cancer Society. 相似文献20.
Diagnostic accuracy of p16INK4a immunohistochemistry in oropharyngeal squamous cell carcinomas: A systematic review and meta‐analysis
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Elena‐Sophie Prigge Marc Arbyn Magnus von Knebel Doeberitz Miriam Reuschenbach 《International journal of cancer. Journal international du cancer》2017,140(5):1186-1198
The accurate diagnosis of human papillomavirus (HPV) causality in oropharyngeal squamous cell carcinomas (OPSCC) is likely to influence therapeutic decisions in affected patients in the near future. We conducted a systematic review and meta‐analysis to determine the diagnostic accuracy of p16INK4a immunohistochemistry (IHC) to identify HPV‐induced OPSCC. We identified all studies that performed p16INK4a IHC (index test) and HPV E6/E7 mRNA detection using an amplification‐based method (gold standard to indicate a transforming relevance of HPV) in OPSCC. Testing with one or more comparator tests (HPV DNA PCR, HPV DNA in situ hybridization (ISH) and p16INK4a IHC/HPV DNA PCR combined testing) was an optional criterion for inclusion. Among 1,636 retrieved studies 24 fulfilled the inclusion criteria. The pooled sensitivity of p16INK4a IHC, HPV DNA PCR, HPV DNA ISH and p16INK4a IHC/HPV DNA PCR combined testing was 94% (95%‐confidence interval (CI) 91–97%), 98% (CI 94–100%), 85% (CI 76–92%) and 93% (CI 87–97%), respectively. The pooled specificity was 83% (CI 78–88%), 84% (CI 74–92%), 88% (CI 78–96%) and 96% (CI 89–100%), respectively. p16INK4a IHC/HPV DNA PCR combined testing was as sensitive as either p16INK4a IHC or HPV DNA PCR alone but significantly more specific than either separate test. In conclusion, p16INK4a IHC is highly sensitive but moderately specific to diagnose HPV‐transformed OPSCC when used as a single test. Combined p16INK4a IHC and HPV DNA PCR testing significantly enhances specificity while maintaining high sensitivity. This diagnostic test combination thus represents an attractive testing strategy for the reliable diagnosis of HPV‐induced OPSCC in the clinical setting and may constitute an inclusion criterion for future therapeutic trials. 相似文献