Routine Cervical Cytology Research Articles

HPV testing in routine cervical screening: cross sectional data from the ARTISTIC trial

To evaluate the effectiveness of human papillomavirus (HPV) testing in primary cervical screening. This was a cross-sectional study from the recruitment phase of a prospective randomised trial. Women were screened for HPV in addition to routine cervical cytology testing. Greater Manchester, attendees at routine NHS Cervical Screening Programme. In all, 24 510 women aged 20–64 screened with liquid-based cytology (LBC) and HPV testing at entry. HPV testing in primary cervical screening. Type-specific HPV prevalence rates are presented in relation to age as well as cytological and histological findings at entry. In all, 24 510 women had adequate cytology and HPV results. Cytology results at entry were: 87% normal, 11% borderline or mild, 1.1% moderate and 0.6% severe dyskaryosis or worse. Prevalence of HPV decreased sharply with age, from 40% at age 20–24 to 12% at 35–39 and 7% or less above age 50. It increased with cytological grade, from 10% of normal cytology and 31% of borderline to 70% mild, 86% moderate, and 96% of severe dyskaryosis or worse. HPV 16 or HPV 18 accounted for 64% of infections in women with severe or worse cytology, and one or both were found in 61% of women with severe dyskaryosis but in only 2.2% of those with normal cytology. The majority of young women in Greater Manchester have been infected with a high-risk HPV by the age of 30. HPV testing is practicable as a primary routine screening test, but in women aged under 30 years, this would lead to a substantial increase in retesting and referral rates. HPV 16 and HPV 18 are more predictive of underlying disease, but other HPV types account for 30% of high-grade disease.

Asymptomatic primary peritoneal carcinoma presenting as adenocarcinoma on routine cervical cytology

Asymptomatic primary peritoneal carcinoma presenting as adenocarcinoma on routine cervical cytology

The prognostic significance of inflammation in invasive carcinoma of the breast

Rapid rescreening was established in our laboratory in 1995, following the publication of several studies indicating improved sensitivity for the detection of abnormalities in cervical smears. During the study period, 285,841 negative smears (representing 89.09% of the total workload) were rapidly rescreened. A total of 7,650 (2.68%) were identified as abnormal or suspicious and selected for full rescreening. Of these, 228 cases were considered abnormal following pathologist review and resulted in the issue of an amended report. This represents an increased detection rate for all abnormalities of 0.08%. Of the cases with histological follow-up, a high grade epithelial abnormality (HGEA) was confirmed in 31% of cases and a low grade epithelial abnormality (LGEA) in 42%.We conclude that rapid rescreening is easily incorporated into the daily workflow of a large routine cervical cytology laboratory. Our results support conclusions from previous studies that rapid rescreening is an effective quality control technique resulting in the detection of increased numbers of abnormal smears.

Routine cervical cytology has no role after primary chemoradiation for cervical cancer

CytopathologyVolume 16, Issue 6 p. 315-316 Routine cervical cytology has no role after primary chemoradiation for cervical cancer N. Singh, N. SinghSearch for more papers by this authorE. Titmuss, E. TitmussSearch for more papers by this authorA. Taylor, A. TaylorSearch for more papers by this authorM. E. B. Powell, M. E. B. PowellSearch for more papers by this author N. Singh, N. SinghSearch for more papers by this authorE. Titmuss, E. TitmussSearch for more papers by this authorA. Taylor, A. TaylorSearch for more papers by this authorM. E. B. Powell, M. E. B. PowellSearch for more papers by this author First published: 22 November 2005 https://doi.org/10.1111/j.1365-2303.2005.00234.xCitations: 2 Dr Naveena Singh, Department of Histopathology, Barts and the London NHS Trust, St Bartholomew's Hospital, West Smithfield, London ECIA 7BE, UK. Tel.: +44(0) 20 7601 8448; Fax: +44(0) 20 7601 8543; E-mail: n.singh@bartsandtheLondon.nhs.uk Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume16, Issue6December 2005Pages 315-316 RelatedInformation

???Atypical Condyloma??? With Bizarre Cells Mimicking Invasive Keratinizing Squamous Cell Carcinoma

Background: The general cytologic features of the keratinizing form of squamous cell carcinoma are well characterized and include pleomorphic squamous cells present singly or in loosely cohesive aggregates. Abnormal shapes including tadpole/spindled or heavily keratinized cells and nuclear pleomorphism with chromatin abnormalities can all be seen. However, Meisels et al described an unusual form of human papillomavirus infection of the cervix (“atypical condyloma”) that can closely mimic the cytology of keratinizing squamous cell carcinoma. We herein report 2 cases where bizarre human papillomavirus associated changes were noted. One case was associated with tumor diathesis. Both were interpreted as squamous cell carcinoma on cytology. Materials and Methods: The patients were a 34-year-old woman (case A) and 37-year-old woman (case B), with no significant past gynecologic history for case A and unknown for case B. Each patient had a routine screening conventional cervical cytology smear sent for evaluation at Northwestern Memorial Hospital. Results: Cytology showed squamous epithelial cells with pleomorphism of cell size, shape, and nuclei. Morphologic features noted included large or “monstrous,” bizarre cells with hyperchromatic, somewhat smudgy nuclei. Cytoplasmic orangeophilia and karyorrhexis were also present. However, nucleolar prominence and tumor diathesis were lacking in case A and noted in case B. Follow-up surgical biopsy showed moderate dysplasia with bizarre cells (case A) and squamous cell carcinoma with bizarre cells (case B). Conclusion: Human papillomavirus–associated cytopathic effect can mimic invasive squamous cell carcinoma. Awareness of this phenomenon is important for accurate classification of these lesions.

Cervical HPV infection and neoplasia in a large population-based prospective study: the Manchester cohort.

Cytology and histology records and cervical samples for HPV assay were obtained from a prospective cohort of 49 655 women attending clinics for routine cervical cytology in or near Manchester between 1988 and 1993. The women were followed up for cytological abnormality and neoplasia through the cytology laboratory's records. HPV at entry was assayed in an age- and period-stratified random sample of 7278 women and in prevalent and incident CIN3 cases. The prevalence of newly diagnosed CIN3 increased with time since last normal smear, indicating that most cases persist for several years. CIN3 prevalence did not increase further for screening intervals exceeding 5 years, however, suggesting that CIN3 eventually regresses cytologically. CIN2 prevalence increased less steeply with screening interval, while the prevalence of lesser abnormality was almost independent of screening interval. The prevalence of oncogenic HPV at entry declined from 19% among women aged under 25 to less than 3% at age 40 or above. Oncogenic HPV infection was strongly predictive of subsequent CIN3 (OR 17.2, 95% CI 10.4–28.4), but only weakly related to CIN2 (OR 2.3, 95% CI 0.5–10.7) and lesser abnormality (OR 1.4, 95% CI 0.8–2.5). At current incidence rates, the lifetime risk of developing CIN3 will be 9% in this population. The cumulative risk of CIN3 diagnosis among cytologically normal women with oncogenic HPV detected at entry was 28% (CI 18–43%) after 14 years. Persistence of oncogenic HPV may be more sensitive and specific than cytology for early detection of CIN3 and invasive cancer.

Significance of inflammatory smears in cervical cytology

The study was undertaken with the aim to evaluate association between inflammatory changes in the cervix with different predisposing factors related to cervical carcinogenesis. Routine outpatient cervical cytology has been carried out in 19,449 women between September 1991 to August 2002 at Queen Mary's Hospital Lucknow and 8354 of them have revealed inflammatory smears (42.9%). Inflammation was found to be associated with trichomonal infection and mild dysplasia (LSIL) in 4.8% and 5.1 % of cases respectively. Both these associations were pronounced in younger women upto 30 years of age. Further the inflammatory smears were frequently seen in women with clinical lesions of cervix (35.1%) and those complaining of vaginal discharge (13.7%). The study points out the need for adequate treatment of inflammation detected on cytology and post-intervention cytology checkup to rule out any persistence, which must be investigated by colposcopy to detect any precancerous manifestations in the cervix.

Posters. P12 Is there any role for routine cytology after chemoradiation for cervical cancer?

Aim Cervical cytology is performed routinely as part of the follow‐up protocol following chemoradiation treatment for cervical cancer. This retrospective review assesses the impact cytology has on the management of patients.Methods Women treated with concurrent chemoradiotherapy for cervical cancer at St Bartholomew's hospital between April 1998 and December 2002 were identified. All cervical cytology results for these patients have been reviewed, and correlated with the site and timing of relapse.Results A total of 69 patients were treated: 58 (84%) had squamous cell carcinoma and 11 (16%) had adenocarcinoma. After median follow‐up of 16 months (4–53), 28 (40%) patients have relapsed. A total of 152 cytology results were available for 51 patients. 18 tests were reported as atypical and five suspicious of malignancy, but subsequent tests show no evidence of recurrence in these 13 (25%) patients. Seventeen patients have developed pelvic relapse. Of these, nine patients had cytology during follow‐up. One patient clinically had a vaginal mass confirmed as malignancy on cytology. The other eight patients had normal cytology within 6 months of clinical disease.Conclusions The pattern of relapse following radical chemoradiation is such that routine cervical and vaginal vault cytology has no indication in the absence of clinical suspicion of disease. The test has questionable sensitivity in this setting because there is a high incidence of false‐positive results that lead to unnecessary investigations. Cytology is valuable for detecting pre‐invasive and pre‐clinical disease, but neither role applies to this patient group.

Cervical Cancer

Worldwide about half a million new cases of cervical cancer occur each year. The incidence is about three times higher in resource-poor countries compared with more developed countries. The disease is reasonably well controlled in countries where routine cervical cytology for detection of premalignant precursors (cervical intraepithelial neoplasia; CIN) is available.Since the causal link between infection by so-called high-risk types of human papillomaviruses (HPV 16, 18 and others) and cervical cancer has been firmly established, the development of virus-specific vaccines has become a major activity both in the academic and corporate sectors. During the natural history of cervical cancer, there are different possible windows for vaccination: (i) prevention of infection that is conferred by neutralizing antibodies can be achieved by immunization with virus-like particles (VLP). Clinical trials with HPV 16 VLPs in humans demonstrated the safety and immunogenicity of the vaccine. Analysis of clinical endpoints such as prevention of infection, CIN and ultimately cervical cancer will require a longer follow-up time; (ii) HPV-as-sociated cervical diseases can also possibly be prevented by postexposure vaccination. As persistent HPV infection appears to be a prerequisite for the development of a malignant tumor, the viral proteins expressed during this state (e.g. E6, E7) are potential targets for cytotoxic T-cell responses to eliminate the infection. Since the target population for this vaccination strategy will consist of mostly young sexually active women that are at risk for reinfection or are potential carriers of infectious virus, it seems to be reasonable to induce a protective immunity via neutralizing antibodies as well. Chimeric virus like particles (CVLP) containing both the L1 (with or without L2) and E7 proteins are promising tools to achieve this goal; and (iii) treatment of cervical cancer by HPV E6/E7-specific immune therapy will most likely only be successful as an adjuvant strategy along with other therapies. On the other hand, based on the data from the first clinical trials, the option of curing precursor lesions by HPV-specific vaccination is considered promising.

CERVICAL CYTOLOGY DURING PREGNANCY

To clarify the clinical significance of uterine cervical cytology during pregnancy, we analyzed the incidence of cervical cytology and its accuracy. Of the 1,593 pregnant women underwent cervical cytology, the patients with abnormal cytology were followed up and performed histological confirmation on colposcopic biopsy specimen. An incidence of abnormal cytology and cervical neoplasm during pregnancy were 1.63% (26 cases) and 0.82% (13 cases), respectively. The incidence of abnormal cytology in the pregnant women was significantly higher than that (0.9%) in mass-screened, non-pregnant 214,375 women under the age of 45 years (P < 0.001). There was no significant difference of the incidence of cervical neoplasm between in the pregnant women and in mass-screened, non-pregnant women (0.82% vs. 0.46%). The accuracy of cervical cytology during pregnancy was 45.0% and this was not significantly different from that (27.6%) in the mass-screened, non-pregnant women. Since, cervical screening cytology for uterine cervical cancer in the pregnant women as shown in this study, has an equal effectiveness to that in the mass-screened non-pregnant women, routine cervical cytology is highly recommended to performed during pregnancy. In addition, management of pregnant women with abnormal cytology was discussed in this article.

Psammoma bodies in cervicovaginal smears

Objective: To estimate the prevalence of psammoma bodies in routine cervical cytology specimens and describe clinical diagnoses associated with them in pre- and postmenopausal women. Methods: We identified all reports that contained psammoma bodies from a retrospective review of 34,816 cytology reports over 4 consecutive years from the computerized pathology database at Yale New-Haven Medical Center. Slides were reviewed to confirm and qualify psammoma bodies. Medical records of women with psammoma bodies were reviewed and information on follow-up was collected. Results: We identified 18 women with psammoma bodies on their Papanicolaou smears. The median age was 49.5 years (range 17–78 years). Seven of eight postmenopausal women had gynecologic malignancies. Five presented with postmenopausal bleeding and had uterine serous or clear-cell carcinomas. One presented with a pelvic mass that was ovarian serous carcinoma. Another had a serous carcinoma of the fallopian tube with only psammoma bodies on Papanicolaou smears. Only one of the remaining 11 nonmalignant cases was a postmenopausal woman. Conclusion: The prevalence of psammoma bodies in consecutively screened Papanicolaou smears was 18 of 34,816. Psammoma bodies on Papanicolaou smears are ominous in postmenopausal women. Their presence in asymptomatic premenopausal women warrants further evaluation, but not necessarily surgical exploration.

Prevalence of bacterial vaginosis in women attending one of three general practices for routine cervical cytology

A prospective observational study of asymptomatic women from three different general practices was set up to establish the incidence of bacterial vaginosis (BV). The study group comprised 287 women recalled to their general practitioner's surgery for routine cervical smears. The prevalence of an abnormal vaginal flora was about the same in women attending the 3 practices. Nearly 14% of women had abnormal vaginal flora and about 9% had BV on gram stain examination of vaginal secretions. This was 2-3 times more common than findings consistent with vaginal candidiasis (3.8%). Significant numbers of women with BV had received antifungal therapy suggesting a misdiagnosis. Because of its potential complications, women should be offered screening for BV in a well-women setting and, if found, should be treated if symptomatic or at risk of adverse obstetric or gynaecological sequelae.

Identifying Women With Cervical Neoplasia

ContextA Papanicolaou (Pap) test result of atypical squamous cells of undetermined significance (ASCUS) presents a clinical challenge. Only 5% to 10% of women with ASCUS harbor serious cervical disease, but more than one third of the high-grade squamous intraepithelial lesions (HSILs) in screening populations are identified from ASCUS Pap test results.ObjectiveTo determine whether human papillomavirus (HPV) DNA testing of residual material from liquid-based Pap tests and referral of cases found to be HPV-positive directly to colposcopy could provide sensitive detection of underlying HSILs in women with ASCUS Pap results, compared with repeat Pap testing.Design and SettingNatural history of women with ASCUS Pap smear results, all of whom had liquid-based cytology, HPV testing, and subsequent repeat Pap tests and colposcopy with histologic evaluation, conducted at 12 gynecology clinics in a large managed care organization between October 1995 and June 1996.ParticipantsFrom a cohort of 46,009 women who had routine cervical examinations, 995 women with Pap test results of ASCUS who consented to participate were identified.Main Outcome MeasuresCervical histology, HPV test results, and repeat Pap smear results, and sensitivity of HPV testing to identify patients found to have HSIL+ histology.ResultsOf 995 participants with ASCUS Pap test results, 973 had both a definitive histologic diagnosis and HPV result. Sixty-five (6.7%) had histologic HSIL or cancer. For women with histologic HSIL+, the HPV test was positive in 89.2% (95% confidence interval [CI], 78.4%-95.2%), and the specificity was 64.1% (95% CI, 60.9%-67.2%). The repeat Pap smear result was abnormal in 76.2% (95% CI, 63.5%-85.7%). Triage based on HPV testing only or on repeat Pap testing only would refer similar proportions (approximately 39%) to colposcopy. The sensitivity of HPV DNA testing for HSIL was equivalent to, if not greater than, that of the repeat Pap test. We further estimated that an HPV-based algorithm including the immediate colposcopy of HPV-positive women, and then repeat Pap testing of all others, would provide an overall sensitivity of 96.9% (95% CI, 88.3%-99.5%).ConclusionsFor women with ASCUS Pap tests, HPV DNA testing of residual specimens collected for routine cervical cytology can help identify those who have underlying HSIL. By testing the specimen collected at initial screening, the majority of high-risk cases can be identified and referred for colposcopy based on a single screening.

Identifying women with cervical neoplasia: using human papillomavirus DNA testing for equivocal Papanicolaou results.

A Papanicolaou (Pap) test result of atypical squamous cells of undetermined significance (ASCUS) presents a clinical challenge. Only 5% to 10% of women with ASCUS harbor serious cervical disease, but more than one third of the high-grade squamous intraepithelial lesions (HSILs) in screening populations are identified from ASCUS Pap test results. To determine whether human papillomavirus (HPV) DNA testing of residual material from liquid-based Pap tests and referral of cases found to be HPV-positive directly to colposcopy could provide sensitive detection of underlying HSILs in women with ASCUS Pap results, compared with repeat Pap testing. Natural history of women with ASCUS Pap smear results, all of whom had liquid-based cytology, HPV testing, and subsequent repeat Pap tests and colposcopy with histologic evaluation, conducted at 12 gynecology clinics in a large managed care organization between October 1995 and June 1996. From a cohort of 46009 women who had routine cervical examinations, 995 women with Pap test results of ASCUS who consented to participate were identified. Cervical histology, HPV test results, and repeat Pap smear results, and sensitivity of HPV testing to identify patients found to have HSIL+ histology. Of 995 participants with ASCUS Pap test results, 973 had both a definitive histologic diagnosis and HPV result. Sixty-five (6.7%) had histologic HSIL or cancer. For women with histologic HSIL+, the HPV test was positive in 89.2% (95% confidence interval [CI], 78.4%-95.2%), and the specificity was 64.1 % (95% CI, 60.9%-67.2%). The repeat Pap smear result was abnormal in 76.2% (95% CI, 63.5%-85.7%). Triage based on HPV testing only or on repeat Pap testing only would refer similar proportions (approximately 39%) to colposcopy. The sensitivity of HPV DNA testing for HSIL was equivalent to, if not greater than, that of the repeat Pap test. We further estimated that an HPV-based algorithm including the immediate colposcopy of HPV-positive women, and then repeat Pap testing of all others, would provide an overall sensitivity of 96.9% (95% CI, 88.3%-99.5%). For women with ASCUS Pap tests, HPV DNA testing of residual specimens collected for routine cervical cytology can help identify those who have underlying HSIL. By testing the specimen collected at initial screening, the majority of high-risk cases can be identified and referred for colposcopy based on a single screening.

Detection of false-negative papanicolaou smears by rapid rescreening in a large routine cervical cytology laboratory

Rapid rescreening was established in our laboratory in 1995, following the publication of several studies indicating improved sensitivity for the detection of abnormalities in cervical smears. During the study period, 285,841 negative smears (representing 89.09% of the total workload) were rapidly rescreened. A total of 7,650 (2.68%) were identified as abnormal or suspicious and selected for full rescreening. Of these, 228 cases were considered abnormal following pathologist review and resulted in the issue of an amended report. This represents an increased detection rate for all abnormalities of 0.08%. Of the cases with histological follow-up, a high grade epithelial abnormality (HGEA) was confirmed in 31% of cases and a low grade epithelial abnormality (LGEA) in 42%. We conclude that rapid rescreening is easily incorporated into the daily workflow of a large routine cervical cytology laboratory, Our results support conclusions from previous studies that rapid rescreening is an effective quality control technique resulting in the detection of increased numbers of abnormal smears.

Correlation between endometrial cells on Papanicolaou smear and endometrial carcinoma.

A retrospective study was done to assess the correlation between endometrial cells on routine cervical cytology and carcinoma of the endometrium. In a 4-year period, endometrial cells of some type were identified on the Papanicolaou (Pap) smears of 61 women, of whom 52 had further diagnostic evaluation of the endometrium. Data were analyzed with a multivariate stepwise logistic regression. The results indicated an association of endometrial cells in Pap smears with carcinoma of the endometrium in seven patients (13.5%). In 45 patients (86.5%), the final diagnosis was benign. Factors that impacted the diagnosis of carcinoma were the findings of atypical or cancerous endometrial cells on Pap smear and abnormal vaginal bleeding. These data indicate the importance of further diagnostic evaluation with endometrial sampling in postmenopausal patients with endometrial cells seen in Pap smears, especially those with abnormal bleeding.

Cost‐effectiveness of routine cytological cervical surveillance following treatment for carcinoma of cervix

Objectives: The cost‐effectiveness of routine cervical cytology during follow‐up after treatment for carcinoma of cervix is examined. Subjects: All patients having routine follow‐up smears during the financial year 1993–1994. A total of 212 patients generated 311 smears, 96 had an intact cervix and 116 had surgical removal as part of their treatment. Ninety‐one patients with intact cervices and 109 without were evaluable. Results: Nine recurrences were detected, in every case this was expected, based on clinical findings. In two of these the smear was reported as normal. Two hundred and thirty smears were from entirely asymptomatic patients. Conclusions: Limiting cervical smears to those who are symptomatic, or where an abnormality is found on examination, would save approximately £3500 per year. This cost needs to be set beside the possibility of detecting an asymptomatic recurrence at an early stage; as reported by others. This suggests that the impact of this strategy is limited. A randomized trial with prospective economic assessment would be the only way to evaluate the cost‐effectiveness of routine cervical smears in the follow‐up of patients treated for cancer of cervix.

HPV testing improves cervical screening.

Testing for human papilloma virus (HPV) might be a useful adjunct to routine cervical cytology in young women, according to new research.

Cervical Cytology and Conservative Management of Cervical Neoplasias During Pregnancy

To elucidate the clinical significance of cervical cytology during pregnancy, 7,725 pregnant women were examined. Abnormal cytologic findings were recorded in 65 cases (0.8%). Colposcopically directed punch biopsies revealed cervical dysplasia and carcinoma in 27 cases (0.35%). The incidences in a massive examination for 714,119 women in Osaka Prefecture were 1.1% and 0.25%, respectively. Cytologic findings of the patients with cervical neoplasia during pregnancy agreed well (76%) with their histologic findings. Colposcopically, the squamo-columnar junction was visible in many cases, and white epithelium was most commonly observed during pregnancy. Pre- and postpartum follow-up study revealed that progression from dysplasia was seen only in two (20%) of 20 cases. Laser conization was performed on six women during pregnancy, and four were microinvasive carcinoma, all of which underwent normal vaginal delivery without any complication from conization. These results suggest that routine cervical cytology must be performed during pregnancy, and cytologic and colposcopic diagnosis may supply enough data to avoid unnecessary biopsies. Moreover, laser conization is recommended as an excellent diagnostic and therapeutic procedure for women with microinvasive carcinoma during pregnancy.

Surgical Management of Early Invasive Cancer of the Cervix Associated With Pregnancy

The simultaneous occurrence of carcinoma of the cervix in pregnancy is uncommon. In a prospective study of 397 patients undergoing type III radical hysterectomy for early invasive cancer of the cervix, 18 were pregnant at the time of surgery; 4 of these were operated after delivery elsewhere. Two others had a type I extrafascial hysterectomy. The incidence was 1 in 4077 deliveries. The clinical and histological characteristics of these patients are presented. Routine speculum examination and cervical cytology in all pregnant patients early in pregnancy are vital for early diagnosis. Bleeding in pregnancy should not automatically be assumed to be caused by pregnancy-related conditions. The strategies in surgical management are discussed. Radical hysterectomy in pregnancy is safe. No major complications were encountered; the mean blood loss was 1.4 liters. The incidence of pelvic node metastases was similar to that seen in nonpregnant patients. The overall 5-year survival rate was 77.7%. Of the 4 patients who died, 3 presented in the puerperium; all succumbed within 27 months. Poor histological prognostic features contributed to the significantly poorer survival in the puerperal patients (P = 0.0445). The 5-year survival in those presenting during the antepartum period (92.8%) was, however, similar to that in the nonpregnant patients. Metastases to the placenta or fetus were not encountered.