Results of longterm hospital based cytological screening in asymptomatic women

Routine cytological screening has been carried out in 27,062 asymptomatic women attending Gynaec and Family Planning O.P.D. of Queen Mary's Hospital, Lucknow, India (April 1971-December 2004). Incidence of squamous intraepithelial lesion (SIL) was found to be 5.9% in the series, while cervical malignancy was seen in 0.6% of cases. The study highlighted the immense utility of cytological screening in minimizing the incidence of carcinoma cervix in the segment of the urban population screened, as the incidence dropped down to 0.5% in the second half from 1.1% noticed in the first half of the screening period. The study also emphasized the utility of clinically downstaging the cervical cancer as 7,316 women showing clinical lesions of cervix were found to harbor SIL in 15.3% and carcinoma cervix in 1.3% of cases as against the incidence of 2.5% for SIL and 0.6% for frank cancer in women with normal cervix. The investigation into different risk factors involved in cervical carcinogenesis revealed that the incidence of SIL and cancer cervix showed a rise with increasing age and parity and prolonged sexual period. The incidences of both cervical cytopathologies were also higher in women of low socio-economic status while religion was found to have no bearing on the occurrence of the disease. Among the four sexually transmitted diseases (STDs) diagnosed in the cervical smears, Trichomonas vaginalis was found to be more prevalent (2.6%), while human papillomavirus (HPV) and Herpes simplex was seen in 0.4 and 0.2% of cases, respectively Herpes simplex was found to have strong affinity with both SIL and carcinoma cervix, while only SIL incidence was high with HPV infection. The study emphasizes need of proper education to women of low socio-economic class for creating awareness regarding hazards and risk factors of cervical cancer as well as management and cure of the disease.     

Squamous intraepithelial lesions in cervical smears of human immunodeficiency virus-seropositive adolescents

Various authors have reported a high rate of human papillomavirus (HPV) infection and HPV-related neoplasias in human immunodeficiency virus (HIV)-seropositive women. On the other hand, young women are most susceptible to cervical infection because of immaturity of the cervix, as it appears that HPV has more access to the basal cells of the differentiating epithelium. The purpose of the present work was to study cervical smears of 82 adolescent HIV-seropositive women (13–21 years of age) to search for cytological evidence of cervical intraepithelial neoplasias. Twenty-one cases showed characteristic features of HPV infection and squamous intraepithelial lesions (SIL; 25.6%). Sixteen cases aged from 17 to 21 years (mean age 19.5 years) had low-grade SIL (LSIL; 19.5%) and five cases aged from 18 to 21 years (mean age 20.2 years) had high-grade SIL (HSIL; 6.1%). There was no significant difference between the mean age of patients with LSIL and HSIL. Two cases had atypical squamous cells of undetermined significance (ASCUS). In the present work it was found that HIV-seropositive adolescents have a high risk for preneoplastic lesions of the cervix (25.6%) as well as a high incidence of more aggressive lesions (6.1% of HSIL) when compared to the general population of adolescents. As it can be assumed that, if the age of acquisition of the infection in both groups (in the general population and HIV-seropositive women) is the same, it is probable that HIV infection in adolescents not only increases the frequency of HPV infections but also facilitates the evolution to more aggressive preneoplastic lesions of the cervix due to HPV. Diagn. Cytopathol. 1998;18:91–92. © 1998 Wiley-Liss, Inc.     

Progression of cervical lesions in HIV-seropositive women: a cytological study

It has been reported that cervical intraepithelial lesions have a more aggressive course in HIV-seropositive than in HIV-seronegative women. In the present investigation, the progression of these cervical lesions was studied in a group of HIV-seropositive women. Of 1,587 patients, 200 (12.6%) had a cytological diagnosis of squamous intraepithelial lesion (SIL) or invasive carcinoma. In 409 patients, more than one cytological smear was collected in 3(1/2) years. Progression occurred in 39 cases. In 24 (61.5%), the first diagnosis was benign cellular changes (BCC) and the second was low-grade SIL (LSIL) (1-yr interval in 21 cases); in 11 (28.2%), the first was BCC, and the second, high-grade SIL (HSIL) (1-yr interval in 9 cases); in 2 (5.0%), the first diagnosis was LSIL. and the second, HSIL (1-yr interval); in 2 (5.0%), the first was HSIL, and the second, invasive carcinoma (2-yr interval). These results point to the importance of cervical cytologic surveillance in HIV-seropositive patients.     

Altered expression of desmosomal components in high-grade squamous intraepithelial lesions of the cervix

We have used immunohistochemistry to test the hypothesis that components of the desmosome are disrupted during neoplastic progression of squamous epithelial cells in the uterine cervix. Sections of normal cervix and squamous intraepithelial lesions (SILs) were immunostained for desmosomal proteins and glycoproteins, and results were assessed using a semi-quantitative grading system. No difference between normal cervix and low-grade SIL (LSIL) was found. A significant reduction in expression of desmogleins was seen between high-grade SIL (HSIL) and LSIL (P<0.01) and normal cervix (P<0.001). Desmocollin expression was not reduced significantly, although scores showed significantly greater variation in HSIL compared with LSIL (P<0.05) and normal cervix (P<0.05). There was no significant difference in desmoplakin expression among the three groups. The results suggest that there may be sequential disruption of desmosomal function during neoplastic progression of cervical squamous intraepithelial cells, with downregulation of desmogleins during the progression from LSIL to HSIL and loss of desmocollin expression occurring in some cases of established HSIL.     

Assessing the feasibility of single lifetime PAP smear evaluation between 41-50 years of age as strategy for cervical cancer control in developing countries from our 32 years of experience of hospital-based routine cytological screening

In view of the huge expenditure involved in mass cytological screening as well as lack of cytology manpower in the developing countries, single lifetime screening at 45 yr of age has been suggested as feasible strategy for control of cervical cancer. The present study is aimed at testing this hypothesis in a broader prospective, accommodating women between 41 and 50 yr of age from the data derived from the ongoing long-term hospital-based routine cervicovaginal cytology at Queen Mary's Hospital, Lucknow, India. The cervical smears of 31,032 women have been evaluated cytologically during a span of 32 yr (April 1971-March 2003) for early detection of carcinoma cervix and sexually transmitted diseases (STDs). The incidence of squamous intraepithelial lesions (SIL) was found to be 6.1% while frank malignancy was seen in 0.5% of cases. The following observations were made from the accumulated cytological data: (a) approximately 30% of the total cancer cases was in the age group of 41-50 yr; (b) the maximum number of SIL cases was detected in women between 41 and 50 yr of age (35% of the total SIL cases), and adequate management of these SIL cases would prevent cancer cases from occurring in later years, thus minimizing the maximum incidence of 1.3% observed in women beyond 50 yr of age; (c) the incidence of human papillomavirus (HPV) infection also was found quite high in women between 41 and 50 yr old, the adequate management of which would prevent onset/progression of any premalignant changes in the cervix. Our experience of 32 yr of cytological screening substantiates the hypothesis of single lifetime screening between 41 and 50 yr of age as an effective strategy for control of carcinoma cervix in developing countries like ours.     

Immunohistochemical assessment of p16, COX-2 and EGFR in HPV-positive cervical squamous intraepithelial lesions

The protein capsid L1 of the human papilloma virus (HPV) - a key factor in the cervical carcinogenesis - is considered, together with p16, EGFR and COX-2, a characteristic marker for the evaluation of the malignancy progression and prognostic, in terms of tumoral aggressiveness. The purpose of the present study was to make a comparative assessment between the immunohistochemical pattern of p16, EGFR and COX-2 and immunochemical expression of L1 HPV capsid protein, in low grade and high-grade cervical squamous intraepithelial lesions, in order to determine the relationship of these tumoral markers with the infection status of HPV, and their practical applicability in patients diagnosis and follow-up. The study group included 50 women with cytological and histopathological confirmed LSIL (low grade SIL) and HSIL (high-grade SIL). The immunoexpression of L1 HPV protein was assessed on conventional cervico-vaginal smears and EGFR, COX-2 and p16 were immunohistochemically evaluated on the corresponding cervical biopsies. From all cervical smears, the HPV L1 capsid protein was expressed in 52% of LSIL and 23% of HSIL. From all cervical biopsies, p16 was positive in 64% of LSIL, 82% of CIN2 and 100% of CIN3, EGFR was overexpressed in 67% of HSIL (56% CIN2 and 43% CIN3) and 32% LSIL. For COX-2, the Allred score was higher in HSIL when compared to LSIL. Our data revealed 33 cases belonging to both LSIL and HSIL categories with the same Allred score. Immunochemical detection of L1 capsid protein, on cervico-vaginal smears, indicates an immune status induced by the HPV infection and may offer prognosis information, mainly in LSIL lesions. The assessment of p16, EGFR, and COX-2 allows to an integrative approach for the progression of squamous intraepithelial lesion, associated or not with the HPV infection.     

Results of clinically downstaging cervical cancer in a cytological screening programme

The study was aimed at clinically downstaging cancer of the cervix during a cytological Screening Programme to find out whether such a strategy may help in yielding a large number of early cases of cancer. A cohort of 6,178 women with different cervical lesions were cytologically examined from April 1971 at Queen Mary's Hospital, Lucknow, India. The 8,718 asymptomatic women with healthy cervices were taken as controls. The incidence of cervical dysplasia and malignancy in the study group was found to be 11.2% and 1.9%, which was statistically highly significant compared to control values of 3.3% and 0.02%, respectively. Dysplastic smears were seen maximally in women whose cervix bled to the touch, and the rate of cervical cancer was high in women with suspicious cervix. Dysplastic smears were seen frequently in all age and parity groups, but malignancy was common in women of high age (over 30 years) and high parity (two and above). The incidence of three sexually transmitted diseases, namely Trichomonas vaginalis, Herpes simplex, and condyloma revealed highly significant values, especially in women whose cervix bled to the touch. The study highlights the strategy of clinically downstaging cervical cancer, which is very useful in detecting a large number of dysplasia and frank malignancy cases and also the presence of any associated sexually transmitted pathogens whose treatment would aid in restricting the rising incidence of the dreaded disease in this country. Diagn. Cytopathol. 1998;19:344–348. © 1998 Wiley-Liss, Inc.     

Prevalence of anal cytological abnormalities in women with positive cervical cytology

The objective of this study was to estimate the prevalence of cytological abnormalities of the anal mucosa in women with positive cervical cytology, but without macroscopic anal lesion. Ultimately we postulated if the anal mucosa may be a reservoir of HPV, which would allow the reinfection of cervix. Forty‐nine patients with abnormal cervical cytology were selected for this work. In a period not exceeding one week of collecting cervix cytology, two swab specimens of the anal canal were also collected. Women diagnosed with cervical HSIL by Pap smear were referred for colposcopy with biopsy of the lesions, to confirm the cytologic diagnosis and ablation of the lesion. We demonstrated a high prevalence of anal squamous intraepithelial lesions in patients with cervical squamous intraepithelial lesions (29 of the total of 49 patients = 59.2%). Of the 20 cases of cervical LSIL, 11 (55%) had abnormal anal cytology. Of the 26 cases with cervical HSIL, 16 (61.5%) had abnormal anal cytology. So, there was a discrete higher prevalence of abnormal anal cytology in cases of high‐grade cervical squamous lesions (cervical HSIL). These results help to support the hypothesis that the anal mucosa is a reservoir of HPV, which can be a source of re‐infection for the cervix. However, there was no significant association between the practice of anal sex and the prevalence of anal cytological abnormalities. These facts are epidemiologically important for future programs for population eradication of cervical lesions related to HPV. Diagn. Cytopathol. 2011;39:323–327. © 2010 Wiley‐Liss, Inc.     

Environmental co-factors in HPV carcinogenesis

Epidemiological studies have shown that only a small fraction of women infected with oncogenic HPV types will eventually progress to high-grade intraepithelial lesions (HSIL) and cervical cancer (CC). Because infection by oncogenic HPVs is a necessary but not a sufficient cause of CC, it has been assumed that other factors, acting in conjunction with HPV, influence the risk of transition from cervical HPV infection to cervical malignancy. This paper reviews the epidemiological evidence for the role of environmental co-factors in HPV carcinogenesis as assessed from selected studies that report associations within a well-defined HPV-DNA positive group. Co-factors assessed include parity, use of oral contraceptives, tobacco smoking, infection with other sexually transmitted diseases, and dietary and nutritional factors. Based on the evidence provided by the largest epidemiological studies that using sensitive detection methods allowed for the effects of HPV, it can be concluded that, among HPV positive women, high parity, long-term OC use, smoking, and co-infection with other sexually transmitted agents are the most consistently identified environmental co-factors likely to influence the risk of progression from cervical HPV infection to HSIL and invasive CC. There is limited evidence for a role of dietary factors in HPV carcinogenesis. On-going epidemiological studies will shed more light into the role of these and other co-factors, but if confirmed, these conclusions may imply that multiparous women, women who are smokers, and women on long-term OC use, might need a closer cytological and HPV surveillance than women in the general population.     

Role of socio-economic factors and cytology in cervical erosion in reproductive age group women

A cross-sectional study involving 357 females in the reproductive age group (15-44) was conducted in an urban community of Nagpur with the objective of studying the role of socio-economic factors & cytology in cervical erosion. Cervical erosion was detected in 82 (22.96%) females. Out of these mild dysplasia was seen in 9.75% females & moderate dysplasia in 2.43% females. High percentages of inflammatory smears i.e. (75.68%) were obtained in women with cervical erosion. Cervical erosion was more common in illiterate & women with low literacy status as compared to women with higher education. Majority of cases of cervical erosion (75.6%) were detected in women with high parity. A statistically significant association was found between lower socio-economic status, early age at marriage & ocurrence of cervical erosion (p<0.001 & p<0.01 respectively). The study concludes that socio-economic factors such as illiteracy and low literacy status, lower socio-economic status, early age at marriage and high parity are contributory for the occurrence of cervical erosion and regular cytological screening by Pap smear will help in early detection of carcinoma cervix and thereby reduce the morbidity and mortality caused by the same.     

A clinical study of cervical dysplasia in long-term survivors of allogeneic stem cell transplantation

This retrospective study examined the prevalence of and risk factors for cervical dysplasia and genital human papillomavirus (HPV) infection in 89 female recipients of allogeneic stem cell transplantation (allo-SCT) between 1985 and 2005 who survived for more than 5 years after transplantation. All patients underwent regular gynecologic examination and cervical cytological testing. The incidence rates of cervical cytological abnormalities and HPV infection were calculated. Various clinical parameters were evaluated for association with cytological high-grade squamous intraepithelial lesion (HSIL) posttransplantation to identify risk factors for cervical dysplasia. Multivariate analysis with logistic regression was used to identify independent risk factors for cervical dysplasia after adjusting for confounding factors. Sixty-one of the 89 patients (68.5%) had cervical cytological abnormalities of varying grades, including atypical squamous cells of undetermined significance (ASC-US; 31.5%; 28 of 89), low-grade squamous intraepithelial lesion (LSIL; 10.1%; 9 of 89), and HSIL (27%; 24 of 89). HPV status was available for 43 patients, 12 of whom (27.9%) were HPV-positive. Among the 69 patients with normal cytological cervical smear findings pretransplantation, the incidence of cytological HSIL was 23.2% (16 of 69) posttransplantation. After adjusting for confounding factors, only unrelated HLA-matched donor and the presence of vulvovaginal chronic graft-versus-host disease (cGVHD) were independent risk factors for cervical cytology HSIL after transplantation, with the highest risk among patients with vulvovaginal cGVHD (adjusted odds ratio, 31.97). We conclude that long-term survivors of allogeneic stem cell transplantation are at high risk for cervical cytological abnormalities. Vulvovaginal cGVHD and unrelated HLA-matched donor were the only independent risk factors for cervical cytological HSIL in patients with normal cervical cytology before transplantation. Regular surveillance by gynecologic examination, including cervical cytological testing, in these patients allows for early diagnosis and effective management of cervical abnormality and decreases the burden of this potentially fatal, but treatable, condition.     

Adeno-associated virus is associated with a lower risk of high-grade cervical neoplasia

Adeno-associated virus (AAV) is a ubiquitous human helper-dependent parvovirus which may interact with human papillomaviruses (HPV) to modify a woman's risk of cervical neoplasia. This analysis was nested in a cohort study of low-income women receiving Pap smears as part of their family planning services. We selected cases (55 with high-grade cervical squamous intraepithelial lesions (HSIL) and 162 with low-grade LSIL) and controls (96 women with normal cervical cytology) and analyzed cervical DNA for AAV, using PCR amplification/dot blot hybridization, and HPV, using hybrid capture I. AAV positivity was associated with a significantly reduced risk of HSIL (age and HPV-adjusted odds ratio (aOR) = 0.32) yet not with LSIL (aOR = 0.78); 53.8% of HSIL, 66.9% of LSIL, and 70.7% of controls were AAV+. AAV appears to interact with HPV to reduce SIL risk; relative to the HPV-/AAV+ exposure, the respective aORs for HSIL and HPV+/AAV-, HPV+/AAV+, and HPV-/AAV+ were 17.0, 6.9, and 3.5. AAV+ was not associated with age, race, HPV status, or sexual or reproductive risk factors. These results strongly suggest that AAV may play a protective or inhibitory role in late stage cervical carcinogenesis. This conclusion needs to be verified in additional epidemiologic studies.     

宫颈细胞学鳞状上皮内病变的诊断及风险管理

目的：探讨宫颈细胞学鳞状上皮内病变(squamous intraepithelial lesion,SIL)与组织学的关系,揭示细胞学SIL诊断的系统性风险及管理策略。方法：回顾性分析我院2013~2015年405例SIL,其中205例有组织学检查,比较两种结果的符合程度,对其差异产生的原因进行分析。结果：低度鳞状上皮内病变(low-grade squamous intraepithelial lesion,LSIL)的阳性预测值约71%,而HSIL的阳性预测值达98%以上。结论：细胞学高度鳞状上皮内病变(high-grade squamous intraepithelial lesion, HSIL)与组织学结果一致性良好,而LSIL与组织学结果符合度较差,需要加强对LSIL的管理。     

The clinical significance of "squamous intraepithelial lesion of indeterminate grade" as a distinct cytologic category

The histologic and/or cytologic follow-up of 127 cases of cervical lesions termed "squamous intraepithelial lesion of indeterminate grade" (SIL) on Papanicolaou (Pap) smears by the 2001 Bethesda System was compared with 150 control cases of low-grade SIL (LSIL), high-grade SIL (HSIL), and atypical squamous cells, cannot exclude HSIL (ASC-H). A follow-up diagnosis of cervical intraepithelial neoplasia (CIN) 2 or higher was identified in 22.8% of SIL cases, which was 2.6 times higher than LSIL, 3 times lower than HSIL, and 1.5 times lower than ASC-H. A follow-up diagnosis of CIN 1 was identified in 31.5% of SIL cases, which was 2 times lower than the LSIL group, 1.5 times higher than the ASC-H cases, and 1.8 times higher than the HSIL group. We found that 22.0% of cases diagnosed as SIL were followed up by Pap smears rather than colposcopy and biopsy, compared with about 1% of LSIL and HSIL cases. Because SIL cases have a significant risk of harboring CIN 2 or greater, we recommend follow-up by colposcopy and biopsy.     

An evaluation of the diagnostic and prognostic significance of p16INK4a/p21WAF1/Cip1 immunostaining in squamous intraepithelial lesions of the uterine cervix using liquid‐based cytology specimens

Human papillomavirus (HPV) infection frequently causes squamous intraepithelial lesions (SIL) of the uterine cervix and consequently gives rise to squamous cell carcinoma. It is therefore important to identify cases that potentially develop higher grades of SIL at an early stage of the disease. In this study, we thus investigated whether immunocytochemistry for p21^WAF1/Cip1 and p16^INK4a could be applicable in the diagnosis and the prognostic prediction of SIL in combination with genomic analyses of HPV. The genomic analysis of high‐risk HPV (hrHPV), which was done by reversed dot blotting and by in situ hybridization, and immunocytochemistry were performed on liquid‐based cytological specimens. A cross‐sectional study comprising 145 cases of NILM, ASC‐US, LSIL, and HSIL indicated that the incidence of the positive cases for p16^INK4a and p21^WAF1/Cip1 and hrHPV increased with the grade of SIL. A double positive status for p16^INK4a and p21^WAF1/Cip1 was a significant discriminator between HSIL and LSIL/NILM, even when applied in conjunction with the genomic test for hrHPV (P = 0.006 by logistic regression analysis). However, a prospective study employing 61 NILM/ASC‐US cases, revealed that the p16^INK4a/p21^WAF1/Cip1 immunostaining was not a significant predictor for the progression of SIL, whereas the cytological diagnosis (NILM vs. ASC‐US) and the infection status of hrHPV conferred significant effects on the prognosis. Immunostaining of p16^INK4a and p21^WAF1/Cip1 provides additional information on the cytological diagnosis of SIL. A further analysis using a larger population is warranted to obtain a conclusive result regarding the prognostic significance of p16^INK4a/p21^WAF1/Cip1 immunocytochemistry in the diagnosis of SIL. Diagn. Cytopathol. 2014;42: 125–133. © 2013 Wiley Periodicals, Inc.     

The value of duplicate slides on atypical squamous cells, cannot exclude high-grade intraepithelial lesion

Atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H) category was added to the 2001 Bethesda System. ASC-H accounts for a small percentage (0.2-0.6%) of abnormal Pap smears and includes heterogenous group of lesions. There are more high-grade cervical lesions (30-50%) in ASC-H than ASC-US (10-15%). An accurate Pap diagnosis is crucial for appropriate patient follow-up and treatment. A total of 43 consecutive ASC-H cases were collected from October 2007 to March 2008, and all duplicate and the original slides were reviewed blindly at the end of the study. On review of the duplicate Pap slides, 18 cases had diagnostic SIL cells (15 HSIL, 2 LSIL with ASC-H, and 1 LSIL). The duplicate slides could have potentially changed 18 (41.9%) ASC-H diagnoses to a more definitive SIL diagnosis. On review of the original Pap slides, 8 of these 18 cases also had HSIL cells. Twenty-one follow-up cervical biopsies (21/43, 48.8%) showed 12 CIN 2/3, 4 CIN 1, 1 VAIN 1, 2 cervical polyps, 1 negative for dysplasia, and 1 insufficient for diagnosis. The CIN 2/3 rate was 57.1% (12/21) based on the original ASC-H Pap diagnosis. The CIN 2/3 rates were 80% (8/10) with SIL cells on duplicate slides and 36.4% (4/11) without SIL cases on duplicate slides. Our study suggested that duplicate slides were very useful for further classification of ASC-H, but other ancillary tests might be necessary for some cases. We propose a systematic approach using combined duplicate slides and reflex HPV testing to further classify ASC-H.     

Association between micronucleus frequency and cervical intraepithelial neoplasia grade in Thinprep cytological test and its significance

A micronucleus is an additional small nucleus formed due to chromosomes or chromosomal fragments fail to be incorporated into the nucleus during cell division. In this study, we assessed the utility of micronucleus counting as a screening tool in cervical precancerous lesions in Thinprep cytological test smears under oil immersion. High risk HPV was also detected by hybrid capture-2 in Thinprep cytological test smears. Our results showed that micronucleus counting was significantly higher in high-grade squamous intraepithelial lesion (HSIL) and invasive carcinoma cases compared to low-grade squamous intraepithelial lesion (LSIL) and non-neoplastic cases. Receiver operating characteristic (ROC) curve analysis revealed that micronucleus counting possessed a high degree of sensitivity and specificity for identifying HSIL and invasive carcinoma. Cut-off of 7.5 for MN counting gave a sensitivity of 89.6% and a specificity of 66.7% (P = 0.024 and AUC = 0.892) for detecting HSIL and invasive carcinoma lesions. Multiple linear regression analysis showed that only HSIL and invasive cancer lesions not age, duration of marital life and number of pregnancy are significantly associated with MN counting. The positive rate of high risk HPV was distinctly higher in LSIL, HSIL and invasive cancer than that in non-neoplstic categories. In conclusions, MN evaluation may be viewed as an effective biomarker for cervical cancer screening. The combination of MN count with HPV DNA detection and TCT may serve as an effective means to screen precancerous cervical lesions in most developing nations.     

Intermediate‐grade squamous intraepithelial lesion may be a valid diagnostic/interpretive category

We undertook this study to assess the characteristics of smears with features intermediate between high‐grade squamous intraepithelial lesion (HSIL) and low‐grade squamous intraepithelial lesion (ISIL). We also wanted to determine how these smears correlate with high risk biopsy diagnosis and to compare this with the biopsy correlation of LSIL and HSIL. Seventy‐four squamous intraepithelial lesion (SIL) smears were identified as intermediate‐grade SIL smears taken at colposcopy in a 1 year period. They were correlated with concurrent colposcopically guided biopsies. Thirty‐five percent of cases with intermediate‐grade SIL smears had a biopsy diagnosis of moderate dysplasia or higher as compared with 12% for LSIL 74% for HSIL. This confirmed our hypothesis that intermediate‐grade SIL smears have a rate of biopsy diagnosis of moderate dysplasia or higher intermediate to that of LSIL and HSIL. Diagn. Cytopathol. 2009. © 2008 Wiley‐Liss, Inc.     

Cyclin dependent kinase inhibitor p27Kip1 expression in normal and neoplastic cervical epithelium

AIM: To investigate whether there is loss of the p27Kip1 protein in developing cervical cancer and whether p27Kip1 immunoreactivity has any relation to the proliferative indicator Ki-67. METHODS: The expression of p27Kip1 and Ki-67 was assessed by immunohistochemistry in serial sections from normal epithelium (13), low grade (27) and high grade (19) squamous intraepithelial lesions (LSIL, HSIL), and invasive cervical cancer (23). In the SIL cases the presence of human papillomavirus (HPV) genomic sequences was assessed by in situ hybridisation. The results were evaluated by image analysis, and reported as mean score of the percentage of p27Kip1 and of Ki-67 positive cells in each histological group. RESULTS: In general, p27Kip1 immunostaining was related to squamous differentation, and was intense in normal epithelium (47%), while it was reduced in SIL lesions as an effect of the decreased number of differentiating cells. However, decrease in the p27Kip1 expression was more evident in LSIL (36%) than in HSIL (39%); in the latter, p27Kip1 had a different intraepithelial distribution in that the staining extended to the basal cells. The average levels of p27Kip1 were similar in SIL lesions associated to low, intermediate, and high risk HPV types. Compared with normal epithelium and dysplasia, invasive cancer showed significantly lower p27Kip1 levels (23%). There was no relation between p27Kip1 and Ki-67 labelling indices in any of the histological groups examined. CONCLUSIONS: A reduction in p27Kip1 protein occurs in cervical cancer independently of the proliferative status. The changes in p27Kip1 expression may be related to the unregulated kinetics of developing cervical cancer.