Role Of Papanicolaou Smear In Mapping Out Cervical Epithelial Morphology In Women With Infertility: Modified Bethesda Classification.

BACKGROUND: Papinocolaou smear (PAP) smear has a specificity of 98% in detecting early changes in cervical epithelium in women above 21 years, thus its avocation as a screening tool for cervical cancers worldwide. In Pakistan with a lack of awareness in our population as well as socioeconomic conditions there is no such screening program. Infertility on the other hand affects 22% of women in Pakistan and thus one of the most common cause of physician visits. Both cervical cancers and infertility have sexually transmitted diseases (STD's) as common causes with studies reporting ~75% of women have an STD at-least once during their life, presenting with cervical epithelial cell lesions. Thus, the present study was carried out to identify patterns of cervical cell morphology in women with infertility using PAP smear. METHODS: Cervical smears were taken from infertile women and fertile women (n=150), stained with H&E and PAP stains, and graded according to Bethesda Classification 2001. Analysis of data was done by using SPSS version 20 and MS Excel. RESULTS: The mean age of participants was ~29 years. Epithelial cell morphology of these smears showed significant difference among three groups (p value 0.037) with severity in infertile women. Further in the subgroup of secondary infertile women, there were more abnormal smears as compared to primary as well as a higher grade of severity by Pap smear. CONCLUSIONS: Thus, it is concluded that women presenting with some level of infertility are at a higher risk of having cervical epithelial abnormalities.

Human Papillomavirus Genotyping among Different Cervical Smears in Duhok/Iraq.

Background/Objective: Cervical cancer ranks the second among the most common gynecologic cancers. This study was established to determine the distribution of cervical HPV genotypes among different Pap readings in Duhok/Iraq. Methods: Between January and September-2016, HPV-DNA was tested in 64 women. Genotyping was carried out by the hybridization reverse blot technique. Cervical smears were taken, performed by ThinPrep technique and stained by Pap stain. Results: Twenty six (40.6%) cases were positive for HPV, 12 (46.2%) in normal and 14 (53.8%) in abnormal Pap smears. 39 (19 high-risk and 16 low-risk) genotypes were identified. The high risk group comprised 6 HPV16, 4 HPV18, 2 HPV66, 2 HPV52, 2 HPV39, 1 HPV56, 1 HPV31 and 1 HPV45. The 16 low risk strains encompassed 4 HPV6 strains, 4 HPV71, 2 HPV54 and 2 HPV83, HPV11, HPV61 HPV84, and HPV62. Mixed infections were described in 4 women (6.25%), limited to the NILM, ASC-US and LSIL smears. They included variable admixtures of 7 high risk genotypes, HPV39 (both copies), HPV66 (both copies), HPV52, HPV31, HPV45 and 6 low risk strains: HPV83, HPV6, HPV11, HPV54, HPV62 and HPV71. Conclusions: The higher frequency of HR-HPV than the LR-HPV with identification of 4 mixed cases indicates that our women are at risk of developing cervical cancer. Detection of HR-HPV in NILM and ASC-US smears with restriction of some strains to these 2 categories highlights the great value of HPV genotyping as a surrogate test to pick up unscreened women at risk of developing cervical malignancy particularly when a proper screening program is absent.

The accuracy of the Papanicolaou smear in the screening and diagnostic settings.

OBJECTIVE: We evaluated the performance of the Papanicolaou smear in screening and diagnostic settings. STUDY DESIGN: We analyzed Papanicolaou smear results of 1,850 women recruited into a clinical trial to evaluate an emerging technology for the detection of cervical cancer. Screening and diagnosis groups were based on the history of previous Papanicolaou smear results. We calculated sensitivities, specificities, positive and negative likelihood ratios (LR+ and LR-), receiver operating characteristic curves, and areas under the receiver operating characteristic curve (AUC). RESULTS: In the screening group, by defining disease as cervical intraepithelial neoplasia (CIN) 2,3/cancer or worse and using high-grade squamous intraepithelial lesion (HSIL) as the test cutpoint, the AUC was 0.689, and the LR+ and LR- were 39.25 and 0.67, respectively. In the diagnosis group, the AUC was 0.764, and the LR+ and LR- were 3.79 and 0.56, respectively. By defining disease as human papillomavirus/CIN 1 or worse and HSIL as the test cutpoint, the AUC was 0.586, and the LR+ and LR- were 17.01 and 0.92 in the screening group; in the diagnosis group, the AUC was 0.686, and the LR+ and LR- were 2.77 and 0.75, respectively. CONCLUSIONS: In a screening setting, a Papanicolaou smear result of HSIL or worse is 39 times more likely in a patient with CIN 2,3/cancer than in a patient without it. This compares to 4 times more likely in the diagnostic setting. The magnitude of the positive likelihood ratio observed in the screening group indicated that abnormal Papanicolaou smear results obtained in the screening setting should have more impact on clinical decision making than those from results obtained in the diagnostic setting.

Association between grade of referral smear and high-grade disease among women with biopsy samples showing cervical intraepithelial neoplasia grade 2.

OBJECTIVE: To determine whether the grade of referral smear reflects the frequency of cervical intraepithelial neoplasia (CIN) grade 3 (CIN3) or worse lesions among patients with CIN2 on punch biopsy. METHODS: In a retrospective study, data were reviewed from women with a punch biopsy sample showing CIN2 and a known referral smear who underwent large loop excision of the transformation zone (LLETZ) between January 1, 2013, and January 1, 2016, at Galway University Hospital, Ireland. Data were analyzed by patient age (≤30 and >30 years), referral smear (low and high grade), and LLETZ histology (≤CIN2 and ≥CIN3). RESULTS: Overall, 264 women were included. LLETZ histology of CIN3 or worse was more common among women with high-grade referral smears (63/144 [43.8%]) than among those with low-grade smears (26/120 [21.7%]; relative risk 2.02, 95% confidence interval 1.37-2.96; P<0.001). Among patients younger than 30 years, underlying CIN3 and above was again more frequent among women with high-grade (44/95 [46.3%]) versus low-grade smears (12/56 [21.4%]; relative risk 2.16, 95% confidence interval 1.25-3.73; P=0.004). No difference was recorded in the older age group. CONCLUSION: Although LLETZ can be performed for a CIN2 biopsy and high-grade smear, consideration should be given among young women (<30 years) with low-grade smears whose biopsy histology is incidentally CIN2.

Modified classification of Gram-stained vaginal smears to predict spontaneous preterm birth: a prospective cohort study.

OBJECTIVE: The purpose of this study was to identify women at risk of spontaneous preterm birth through a 4-category Gram-stained vaginal smear method, not restricted to bacterial vaginosis. STUDY DESIGN: This was a prospective cohort study correlating Gram-stained vaginal smears in early pregnancy with spontaneous preterm birth. Smears were categorized as 'normal,' 'bacterial vaginosis-like,' 'grade I-like' (atypical gram-positive rods) or 'purulent grade I' (lactobacilli-dominated smears showing heavy leukorrhea of unknown cause). RESULTS: Normal microflora were associated with a 4-fold decreased risk (95%CI 0.1-0.6, P < .001) of spontaneous preterm birth and an abnormal Gram stain with an overall adjusted odds ratio of 5.2 (95%CI 1.8-14.5, P < .001). The sensitivity of vaginal smear diagnosis for preterm birth increased from 25% with conventional scoring up to 70% with these modified criteria. CONCLUSION: Accounting for atypical gram-positive bacteria and neutrophils on Gram-stained vaginal smears may identify a larger proportion of women at risk of preterm birth compared to diagnosis of bacterial vaginosis alone.

An interactive computer program for teaching residents pap smear classification, screening and management guidelines: a pilot study.

OBJECTIVE: To assess the feasibility, utility and resident attitudes towards an interactive, Web-based computer learning program. STUDY DESIGN: Pretest/ posttest evaluation of an interactive curriculum to teach current recommendations for cervical cancer screening and classification and management of abnormal Pap smears. Thirty-five Obstetrics and Gynecology (OB/ GYN) residents were encouraged to complete a Web-based computer program that consisted of a pretest, 9 educational sections (3 didactic and 6 case based), a posttest and an exit survey. Clinical cases involved virtual case management of patients' cytologic, histologic and colposcopic images. Mastery was set at 82% (or 23/28 correct answers). RESULTS: Thirty-one of the 35 residents (89%) completed the curriculum. No resident demonstrated mastery (82%) on the pretest; 15 of 31 residents demonstrated mastery on the posttest (p = 0.04). Mean improvement for all residents was 9 additional questions answered correctly. All the residents thought that the Web site was useful and covered all the learning objectives and would recommend it to other residents. CONCLUSION: A program to teach current cervical cancer screening, classification and abnormal Pap smear management guidelines was useful, feasible and well accepted by residents in this population.

Evaluation of p16INK4a in cervical lesion of premenopausal and postmenopausal women.

Pap smears of postmenopausal women are often misdiagnosed because of the difficulty in distinguishing atrophic epithelial cells groups only by morphological criteria. In this study we investigated the diagnostic application of immunocytochemical staining of p16INK4a on conventional Pap smear. A total of 137 cervical specimens were enrolled in this study, of which 77 and 60 cervical smears were taken from premenopausal and postmenopausal women, respectively. Two cervical smears were taken simultaneously in 68 women, one for conventional cytology and the other for immunostaining. Additional 69 cervical smears were taken from the archive, decolorized and then used for immunostaining. In premenopausal women 1 out of 14 (7.1%) with negative cytology, 7 out of 24 (29.2%) with low grade squamous intra-epithelial lesion (LSIL), all 35 (100%) with high grade squamous intraepithelial lesion (HSIL) and all 4 (100%) with squamous cell carcinoma (confirmed by histopathology) had positive staining to p16INK4a. In postmenopausal women p16INK4a positivity was observed in 4 out of 7 (57.1%) cases of LSIL, 12 out of 14 (85.7%) cases of HSIL and all 4 out of 5 (80%) different cases of carcinoma (1 cervical adenosquamous carcinoma and 3 cervical squamous cell carcinoma in situ confirmed by histopathology), but none of 34 smears with normal cytology. Twenty smears with normal cytology chosen for the negative control in this study were from the group of postmenopausal women and were as expected negative for p16INK4a immunostaining. In the group of postmenopausal women, 16 out of 60 (26.7%) cases the cytological diagnosis was established on the basis of pl6lNK4a immunostaining as being HSIL. From our preliminary study on a limited number of samples, we can however conclude that pl6INK4a immunostaining is a very useful tool for cytological diagnosis enabling to distinguish HSIL from normal, reactive or inflammatory changes.

Prevalence of human papillomavirus among Croatian women attending regular gynecological visit.

Human papillomavirus (HPV) infection has been identified as major risk factor for cervical intraepithelial neoplasia (CIN) and invasive cervical cancer. About 40 HPV viral types are commonly found in the genital tract. Most HPV infections resolve spontaneously, while persistent infection with oncogenic types, namely HPV 16 and 18 is necessary for CIN to occur and progress to cancer. Cervical screening is presently based on the Pap smear that is designed to diagnose precancerous lesions and cervical cancer The aim of this study was to investigate the prevalence of HPV DNA and to determine HPV types distribution among 361 women attending regular gynecological visit. There were 205 women (29+/-8 years old) without determined abnormal cervical lesions and 156 women (34+/-15 years old) with abnormal Pap smear; low grade squamous intraepitehelial lesions (LSIL, n=69), high grade squamous intraepithelial lesions (HSIL, n=72) and atypical squamous cells of undetermined significance (ASCUS, n=15). HPV DNA detection and genotyping was performed by Hybrid Capture 2 assay and additionally by consensus and type-specific primers directed PCR. The overall prevalence of high-risk HPV (hrHPV) in women with abnormal Pap smears was 67.9% (106/156), of which in ASCUS 33.4% (5/15), LSIL 62.3% (43/69) and HSIL 80.6% (58/72). In HPV positive specimens, HPV 16 was found as predominant type in 60.4% cases, followed by HPV 31 (8.5%), HPV 33 (6.6%) and HPV 18 (3.7%). In the group of women without obvious cervical changes the overall hrHPV prevalence was 35.6% with HPV 16 found in 43.8% cases, followed by HPV 31 (17.8%), HPV33 (9.5%) and HPV18 (6.8%). In both study groups, women with and without cervical lesions, the prevalence of HPVof indeterminate type was 14.2% and 13.7%, respectively. Our results indicate that cervical intraepithelial lesions are largely associated with HPV type 16, followed by HPV types 31, 33, 18 and HPV of indeterminate type. Although there is a significant difference in hrHPV DNA prevalence among two groups, no significant differences between particular hrHPV types distribution were observed.

Organisation of cervical cytology screening in Croatia: past, present and future.

This presentation highlights strengths and weaknesses of cervical cytology screening in Croatia, with particular reference to the opportunistic screening, the use of conventional Papanicolaou (Pap) test and the analysis of some organizational, educational and performance issues that are associated with it. Its aim is to propose measures to improve the efficacy of cervical cytology screening in order to reduce cervical cancer mortality. Currently, in excess of 450,000 Pap tests/ year are examined at 35 laboratories scattered throughout the country. All of these laboratories use standard operating procedures including internal and external quality control. They employ a total of 68 cytologists and 91 cytotechnologists. The sensitivity of cervical screening in Croatia is 90.0%, specificity 98.6%, positive predictive value 92.3%, negative predictive value 98.1% and overall diagnostic accuracy 97.2%. The high diagnostic accuracy of cervical cytology is attributed to the long-standing tradition of education and training of cytologists (postgraduate MSc course since 1967, independent residency since 1974) and cytotechnologists (since 1968). This tradition spanning more than half a century means that today in Croatia there is a developed network of cytology laboratories staffed by highly competent cytologists and trained cytotechnologists. The high accuracy of cancer detection through Pap tests provides strong evidence in support of cervical cytology screening remaining the basic method of prevention for cervical carcinoma. However, some modifications to the current situation are needed. These relate primarily to opportunistic screening. The current screening coverage rate is 68%, although there is capacity, which would allow for all women at risk, i.e. those aged 25-64, to be screened once in three years. The screening coverage relates mainly to those women visiting gynecological out patient clinics for unrelated conditions. A properly organized and controlled national screening programme should replace this. This should be accompanied by the introduction of alternative, highly sensitive methods of sample collection and preparation, such as are available through the introduction of new technologies, e.g. liquid based cytology.

Rate of pathology from atypical glandular cell Pap tests classified by the Bethesda 2001 nomenclature.

OBJECTIVE: To estimate the risk of significant pathology from atypical glandular cell (AGC) Pap tests classified by the 2001 Bethesda system and to assess potential differences in AGC management practices between physician specialties. METHODS: A chart study was conducted to assess outcomes from AGC Pap tests diagnosed during 2001-2005. RESULTS: One hundred thirty-one AGC Pap tests were identified from 84,748 Pap tests. The incidence of AGC was 0.15%. Thirty-nine AGC Pap tests (30%) were excluded from analysis, leaving 92 AGC Pap tests from 82 patients available for review. Thirty-one of 82 women (38%) had significant pathology. Seventeen women (21%) had preinvasive disease: cervical intraepithelial neoplasia 2 or 3, adenocarcinoma in situ and endometrial hyperplasia, whereas 14 women (17%) had invasive adenocarcinomas of the endometrium, cervix, ovary, and rectum. Women who were aged 40 years or younger differed significantly from women aged older than 40 years with regard to final pathology (P = .002). Specifically, they were more likely to have preinvasive disease and less likely to have invasive carcinoma. Recommended management for AGC includes colposcopy with or without biopsy, endocervical curettage, and endometrial biopsy. Sixty-three of 82 (77%) women were managed by recommended guidelines, and there was a statistically significant difference in physician adherence when comparing gynecologists to primary care physicians (87% compared with 50%, P < .001). CONCLUSION: Atypical glandular cell cytology confers a risk (38%) of either preinvasive disease or carcinoma, with the risk of carcinoma increasing significantly for women aged older than 40. Adherence to recommended AGC management guidelines is crucial to identify underlying malignancies. LEVEL OF EVIDENCE: II-2.

Cytomorphologic analysis and histological correlation of high-grade squamous intraepithelial lesions in postmenopausal women.

Atrophy-related epithelial changes often pose a diagnostic difficulty during the interpretation of postmenopausal smears. The objectives of this study are to identify the cytomorphologic features of HSIL, in Pap smears of postmenopausal Pap women, and to investigate the possible criteria that could lead to an inaccurate interpretation and false-positive results. Forty Pap smears that were reported as HSIL in postmenopausal women were reviewed. Follow-up cervical biopsies were available on all cases, of which 6 cases were immunostained for MIB-1 and P16. The following cytomorphologic features were evaluated: smear background, degree of cellularity, cellular arrangement, nuclear size, nuclear membrane irregularity, nuclear/cytoplasmic ratio, hyperchromasia, and chromatin pattern. Significant histological abnormalities were present in 35 out of 40 cases. Of those, 22 (55%) cases had high-grade cervical intraepithelial neoplasia (CIN2 or CIN3), 10 (25%) had CIN-1, 5 (12.5%) had reactive changes in the biopsy, and 3 cases had invasive squamous cell carcinoma. The cytomorphologic features that favored HSIL (P < 0.05) included: increased number of abnormal cells, nuclear membrane irregularities, cellular arrangement, and high nuclear/cytoplasmic ratio. Granular background, nuclear size, hyperchromasia, and abnormal chromatin pattern can be associated with reactive and atrophic changes. Our study showed that cytomorphological features favoring HSIL in postmenopausal smears include increased number of abnormal single cells with high nuclear/cytoplasmic ratio and irregular nuclear membrane. Granular background, nuclear enlargement, abnormal chromatin pattern, and hyperchromasia can be seen in reactive changes, and may lead to inaccurate interpretation.

Screening for cervical cancer and initial treatment of patients with abnormal results from papanicolaou testing.

New techniques for cervical cancer screening and a better understanding of the natural history of human papillomavirus (HPV) and cervical neoplasia have inspired a quest for more rational screening strategies for cervical cancer. Often, screening intervals for women older than 30 years can be expanded safely to every 3 years, and experts now agree that screening may cease after hysterectomy and in elderly women (provided certain criteria have been met). Liquid-based cytology produces more satisfactory specimens than conventional testing and offers the valuable option of treating atypical squamous cells of undetermined significance by "reflex" testing for high-risk types of HPV on the original specimen. Testing for HPV as an adjunct to cervical cytology for primary screening is now considered reasonable for many women older than 30 years.

Clinical significance of unsatisfactory conventional pap smears owing to inadequate squamous cellularity defined by the Bethesda 2001 criterion.

To determine the incidence of clinically significant lesions in long-term follow-up after a diagnosis of inadequate squamous cellularity using former and new criteria, we reviewed conventional Papanicolaou (Pap) smears (January-December 1998) for adequacy based on the Bethesda System 2001 criterion. Of 23,302 Pap smears evaluated in our laboratory, 114 (0.489%) were classified as unsatisfactory and 245 (1.051%) as "satisfactory but limited by" based on the 10% rule. Follow-up information for 5 years was obtained for 172 patients without a concurrent cervical epithelial abnormality: 25 (14.5%) had squamous abnormalities (atypical squamous cells, 22; low-grade squamous intraepithelial lesion, 2; and high-grade squamous intraepithelial lesion, 1). With the Bethesda System 2001 criterion, 167 (97.1%) of 172 smears had inadequate squamous cellularity and 5 (2.9%) were adequate. No differences in the incidence of squamous abnormalities detected on follow-up were noted between patients with unsatisfactory Pap smears owing to inadequate squamous cellularity and patients with satisfactory and negative smears. Our findings raise the question whether patients with unsatisfactory Pap smears and a negative history of gynecologic diseases require repeated Pap smears within 2 to 4 months as suggested by the American Society for Colposcopy and Cervical Pathology guideline.

Bethesda classification of cervicovaginal smears: reproducibility and viral correlates.

Fifty-five cervicovaginal smears from women with squamous intraepithelial lesions (SILs) were independently evaluated on two separate occasions by four cytopathologists using a binary classification system (the Bethesda system). Smears were categorized as low-grade (LSIL) or high-grade (HSIL) using previously published criteria. All women had subsequent cervical biopsies containing human papillomavirus (HPV) DNA amplified with the polymerase chain reaction and typed by restriction fragment polymorphism analysis. Three or more observers agreed on classification in 49 of 55 cases (87%); unanimous diagnoses were rendered in 31 cases (56%). Interobserver and intraobserver reproducibility ranged from fair to near-excellent (kappa values 0.40 to 0.63; 0.63 to 0.74, respectively). HPV types included HPV 16 (27%), 18 (7%), 31 (9%), 35 (4%), 39 (4%), 6 (10%), 11 (2%), novel types (30%), and multiple types (4%). High-risk HPV types (16, 18, 31, 35, and 39) were significantly associated (P = .03) with consensus HSIL diagnoses (agreement of three or more observers). This was primarily because of the strong association of HPV 16 with HSIL (P = .001). After excluding HPV 16, the other high-risk HPV types (18, 31, 35, and 39) were no longer significantly associated with consensus HSIL diagnoses (P > .5). Conversely, LSIL diagnoses were significantly associated with non-high-risk HPV types (all HPV types except 16, 18, 31, 35, and 39; P = .006). Binary cytological classification of cervicovaginal SILs is reproducible among cytopathologists. Such classification correlates well with most low-risk HPV types and with the prototypic high-risk HPV 16 but not with other high-risk HPV types.

Clinical perception of disease probability associated with Bethesda System diagnoses.

The degree to which clinical perceptions of Papanicolaou smear sensitivity contribute to patient mismanagement is uncertain. A voluntary, anonymous questionnaire was mailed to 350 obstetricians/gynecologists (OGYNs) and 350 other primary care providers (PCPs) located in Pennsylvania or Ohio. The clinicians estimated the probability of no disease, dysplasia, and invasive carcinoma for 1 of 7 Bethesda System diagnoses. Differences in probability estimates between provider types and between the clinicians and medical literature data were measured. The response rate was 22.7%. Compared with published values, clinicians estimated similar disease probabilities for many diagnoses. However, for some diagnoses, the probability estimates differed considerably from published values (e.g., overestimation of dysplasia and invasive carcinoma for benign diagnoses and underestimation of dysplasia for some dysplasia diagnoses), and such errors could contribute to patient mismanagement. OGYNs generally were more accurate in probability estimates than PCPs. Methods to convey more accurately these diagnostic disease probabilities should be examined.

Atypical glandular cells of undetermined significance. Outcome predictions based on human papillomavirus testing.

Cases of atypical glandular cells (AGC) diagnosed on liquid-based preparations were culled from a 3-year period. When available, residual cellular material was analyzed for human papillomavirus (HPV) by polymerase chain reaction and correlated with cytologic and histologic (biopsy) outcome. Of 178,994 cytologic cases, 187 (0.1045%) contained AGC compared with 8,740 (4.8828%) atypical squamous cells (ASC) for an AGC/ASC ratio of 0.021. HPV results and follow-up were available for 108 specimens from 106 patients. Depending on the end-point (histologic/cyto-logic), the sensitivity range of HPV testing for significant cervical disease (high-grade squamous intraepithelial lesion [SIL], adenocarcinoma in situ [ACIS], invasive carcinoma) was 83% with a specificity range of 78% to 82%, a positive predictive value of 57% to 61%, and a negative predictive value of 91% to 95%. Fifteen false-positive results included concurrent ASC or low-grade SIL, ASC on follow-up cytology, and previous ACIS with a negative follow-up cone biopsy result. Noncervical glandular neoplasia (including atypical endometrial hyperplasia) was confirmed in 13 cases (1 recurrent), only 2 of which scored positive for HPV. HPV-positive AGC has a substantially higher positive predictive value for significant disease than ASC (61% vs historic 20%) and merits consideration in the triage of patients with atypical endocervical cells not otherwise specified. However, noncervical or other HPV-negative glandular neoplasia must be considered in all patients with AGC, particularly older patients.

Observer variation, dysplasia grading, and HPV typing: a review.

Squamous dysplasia of the cervix is a morphologic continuum that is divided into a number of categories. When the severity of a morphologic abnormality is assessed, whether in a biopsy sample or in an exfoliative smear, there can be significant observer variation. The statistical quantification of this variation, with particular reference to the kappa statistic and the influence of the number of categories utilized on the kappa statistic, is discussed. The contribution of information theory to the understanding of the reasons for observer variation is explored. The use of a binary (Bethesda) system of classification of squamous dysplasia and its validation by comparing consensus diagnoses with human papilloma virus type both in biopsy samples and in smears is reviewed.

Qualification of ASCUS. A comparison of equivocal LSIL and equivocal HSIL cervical cytology in the ASCUS LSIL Triage Study.

Cytologic detection of high-grade squamous intraepithelial lesions (HSILs) is critical to cervical cancer prevention. Therefore, identifying "equivocal HSIL" (ASCUS [atypical squamous cells of undetermined significance]-H) may be useful. Accordingly, we compared findings associated with "equivocal low-grade SIL" (ASCUS-L), ASCUS-H, and HSIL using data from the ASCUS LSIL (low-grade squamous intraepithelial lesion) Triage Study. The frequency of oncogenic human papillomavirus (HPV) DNA detection and underlying lesions cervical intraepithelial neoplasia (CIN) 2 or worse or CIN 3 or worse in women with ASCUS-H was intermediate between that of ASCUS-L and HSIL. Oncogenic HPV DNA was associated with 85.6% of ASCUS-H ThinPreps and 69.8% of ASCUS-H smears. Histopathologic lesions CIN 2 or worse were associated with 40.5% of ASCUS-H ThinPreps and 27.2% of ASCUS-H smears (mostly CIN 3). Nevertheless, numerically more lesions CIN 2 or worse were preceded by ASCUS-L than by ASCUS-H because ASCUS-L was more common. ASCUS-H is an uncommon interpretation that derives clinical usefulness from its high positive predictive value for lesions CIN 2 or worse.

Completeness of excision and follow up cytology in patients treated with loop excision biopsy.

AIMS: To assess the relation between the grade and the status of follow up cytology, the completeness of loop excision biopsies with cervical intraepithelial neoplasia (CIN), and the findings at follow up cytology, as well as the differences between complete and incomplete exclusion, using the odds ratio. Treatment failure was assessed. METHODS: 1600 women with CIN (290 CIN1, 304 CIN2, 1006 CIN3) were followed for a minimum of six months and a maximum of 10 years. A database was created and comparisons performed. The mean age of the patients was 37 years. RESULTS: Excision was complete in over 84% of loops. Residual disease and recurrence of high grade dyskaryosis was more common in women with CIN 3 than CIN 2 or 1. No high grade dyskaryosis was seen in the fifth follow up smear in patients with CIN 1 and CIN 2. Residual, recurrent, and persistent disease was most common in patients with incompletely excised CIN at ectocervical and endocervical margins and deep margins of resection than in patients with completely excised CIN. The odds ratios were significantly higher in the women who had incomplete excision of CIN at ectocervical, endocervical, both ecto- and endocervical, and deep margins of resection compared with those with apparent complete excision of CIN lesions. One patient developed invasive squamous cell carcinoma 44 months after loop excision which showed CIN 3 invading endocervical crypts and extending to both ectocervical and endocervical margins of resection. CONCLUSIONS: At long term follow up, patients with CIN who have residual disease are at increased risk of persistent disease and should therefore be followed up regularly with cytology and colposcopy. The findings support national policy of returning women with treated CIN of any grade to normal recall after five years except for cases of CIN3 where excision was incomplete or equivocal. In these cases follow up with annual smear for 10 years is recommended.