Human papillomavirus testing improves the accuracy of colposcopy in detection of cervical intraepithelial neoplasia

To assess the performance of human papillomavirus (HPV) testing and colposcopy in detection of cervical pathology. A series of 389 women referred for colposcopy due to an abnormal Pap smear had cervical swabs analyzed for oncogenic (high-risk [HR]) HPV types using Hybrid Capture II (HC2) assay. Loop electrical excision procedure cone biopsy (88%) or colposcopic biopsy (11%) was used as the gold standard. Of the atypical squamous cells of undetermined significance (ASCUS) smears, 48% were positive for HR HPV, as compared to 76.3% of low-grade squamous intraepithelial lesions (LSIL) smears. HR HPV was detected in 66.7% and 90% of patients with cervical intraepithelial neoplasia (CIN) 1 and CIN2 (or higher), respectively. The sensitivity of the Pap smear using an ASCUS threshold in detecting high-grade CIN was 94.5% (95% confidence intervals (CI): 91-97%) and that of colposcopy 98.5% (95% CI: 95-99%). The respective specificities were 30% (95% CI: 17-28%) and 35.6% (CI: 29-42%). HC2 test had comparable sensitivity, 90% (95% CI: 85-93%), but higher specificity, 54.3% (95% CI: 47-61%). Combining HC2 test with Pap increased specificity, 66.7% and 41.3% for ASCUS and LSIL cutoff, respectively. The minor-abnormality threshold together with HC2 increased specificity of colposcopy with no changes in sensitivity. High viral load (>100 relative light unit/positive control) was associated with significant disease. HPV DNA testing improves the accuracy of colposcopy in the detection of high-grade CIN in women with ASCUS or LSIL smears.     

Contribution of human papillomavirus testing by hybrid capture in the triage of women with repeated abnormal pap smears before colposcopy referral

OBJECTIVE: The purpose of this work was to evaluate the ability of testing for high-risk human papillomavirus (HPV) types using the hybrid capture technique to predict the presence of cervical intraepithelial neoplasia (CIN) II,III in patients with repeated atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LGSIL) on Pap smears. METHODS: Hybrid capture testing and tissue biopsy were performed on 503 consecutive women with ASCUS or LGSIL on repeated Pap smears who were referred for colposcopy. RESULTS: A highly significant association (P < 0.0001) was found between a positive test for high-risk HPV types and CIN II,III, with an 87.0% positive predictive value and a 95.7% negative predictive value. In 226 women with ASCUS on repeated Pap smears, a positive test for high-risk HPV types had a 85.7% sensitivity and a 97% specificity for CIN II,III. In 277 patients with LGSIL on repeated Pap smears, a positive test for high-risk HPV types had an 88.2% sensitivity and a 94.7% specificity for CIN I,II. Reserving colposcopy examination for women who were positive for high-risk HPV types would have reduced the number of referrals for colposcopy to 24.6% and maintained a sensitivity of 87.0% for CIN II,III. CONCLUSIONS: A positive hybrid capture test for high-risk HPV types was highly sensitive and specific for the presence of CIN II,III in patients with ASCUS and LGSIL on repeated Pap smears. We believe that improved methodology will eventually enable more selective colposcopy referrals without affecting patient safety among these women.     

Comparison of three management strategies for patients with atypical squamous cells of undetermined significance, after six months delay: A three-year experience in an Iranian university hospital

Background: A Pap test result of atypical squamous cells of undetermined significance (ASCUS) presents a clinical challenge. Only 5–10% of women with ASCUS harbour serious cervical disease.
Methods: We screened 3619 women, who attended to Mirza Koochak Khan Hospital at Tehran University of Medical Sciences with Pap smears, of whom 100 returned with ASCUS. After six months, each subject underwent a standard cytology (conventional Pap smear), human papillomavirus (HPV) DNA testing (identifying high-risk HPV types with polymerase chain reaction) and colposcopy with multiple cervical biopsies.
Results: Mean age was 44.09 ± 8.6 years. The estimated prevalence of cervical intraepithelial neoplasia (CIN) II or higher was 4%. When histologically verified high-grade lesions (≥ CIN II) were observed, the relative sensitivity of HPV DNA testing was 100% compared with conventional Pap smear, which performed 75% versus 100% relative sensitivity, respectively, using cytological diagnosis high-grade squamous intraepithelial lesion, or low-grade squamous intraepithelial lesion (LSIL) as the cut-off. Negative and positive predictive values (NPV and PPV) of Pap test were 98.9% and 100%. The NPV and PPV of HPV DNA testing were 100%.
Conclusions: Although less complicated than colposcopy, the repeat Pap smear triage algorithm for ASCUS may underdiagnose some women with high-grade CIN, when compared with colposcopy. Considering the high sensitivity of HPV testing, it may be useful as an alternative to the current policy of six-month repeat cytology for women with ASCUS results.     

High-risk HPV DNA detection by Hybrid Capture II. An adjunctive test for mildly abnormal cytologic smears in women > or = 50 years of age

OBJECTIVE: To determine whether high-risk human papillomavirus (HPV) DNA testing could improve the detection of cervical intraepithelial neoplasia (CIN) and cancer in older women (> or = 50 years old) with mildly abnormal results on conventional cytology. STUDY DESIGN: The study was based on 119 patients aged over 50 (median, 62; range, 50-78) referred for colposcopy with Pap smears reported as atypical squamous cells of undetermined significance (ASCUS) or low grade squamous intraepithelial lesion (LSIL) from February 1997 to September 1998. The presence of high-risk HPV DNA (including HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68) was determined with the Hybrid Capture II (Digene, Inc., Silver Spring, Maryland) microplate method. Cytologic examination by Pap smear was based on the Bethesda System and, cervical biopsy was done via colposcopy. RESULTS: High-risk HPV DNA was demonstrated in 75.6% (34/45) of patients with LSIL and 52.7% (39/74) with ASCUS. Those who were HPV positive were significantly more likely to have CIN or cancer (odds ratio, 33.40; 95% confidence interval, 11.89-93.97; P < .0001). The sensitivity of HPV assay for detection of lesions more severe than CIN 2 was 100%, specificity 64.8%, positive predictive value 66.7% and negative predictive value 100%. CONCLUSION: The addition of a high-risk HPV DNA assay to cytologic examination appears to provide excellent sensitivity and negative predictive value for early detection of high grade CIN or cancer in older women with minimally abnormal Pap smears.     

Clinical results of a split sample liquid-based cytology (ThinPrep) study of 4,322 patients in a Turkish institution

PURPOSE: A prospective study was carried out to compare the efficacy of liquid-based cytology (ThinPrep) with the conventional Pap smear using a split-sample design in a Turkish university hospital outpatient gynecology clinic. METHODS: 4,322 consecutive patients were recruited for the study between 2002 and 2003. All the patients underwent conventional Pap tests followed by a ThinPrep test for screening of cervical cancer. The results were evaluated in terms of the Bethesda III classification. All the patients with abnormal tests underwent colposcopy and directed biopsy. RESULTS: While 2.3% of the specimens were unsatisfactory for evaluation in the conventional Pap test group, this rate was 1.7% for the ThinPrep group. Epithelial cell abnormalities were observed in 42 (1.0%) patients in the conventional Pap test group and in 36 (0.8%) patients in the ThinPrep group. ASCUS was observed in 26 patients in the conventional Pap test group whereas the ThinPrep group had 20 cases of ASCUS as the leading cause of abnormal cytology. Biopsy of these cases revealed CIN 1 in two CIN 2-3 in three and cervical/endometrial adenocarcinoma in three patients. The ThinPrep application led to diagnoses of one additional case of CIN 2-3 and one case of adenocarcinoma among the negative or unsatisfactory for evaluation categories of the conventional Pap test group. CONCLUSION: Despite an adverse bias introduced by the split-sample study design, application of ThinPrep showed an improved rate of specimen adequacy and increased sensitivity for more significant cervical precursor lesions over the conventional Pap test.     

Clinical validation of high risk HPV DNA testing versus ThinPrep cytology for primary cervical cancer screening

Objective(s)To compare the validity of the high risk HPV DNA testing using the hybrid capture II technique (HC-II) to ThinPrep cytology for primary cervical cancer screening.DesignCross sectional pilot study.SettingDepartment of Obstetrics and Gynecology, Taiba Hospital, Sabah Al Salem, Kuwait.MethodsConsecutive 1923 cervical smear samples were taken for ThinPrep cytological screening and hr-HPV DNA testing using HC-II assay. Histological diagnoses were obtained from a total of 426 women who had positive results on screening and a group of women with negative screening and suspicious cervix underwent colposcopy and directed biopsies, and those with cervical precancerous lesions or cancer received appropriate treatment.Main outcome measuresSensitivity, specificity, positive predictive value and negative predictive value of screening methods.ResultsHPV was found positive in 15.5% of cases. 19/22 cases (86.4.1%) with a biopsy diagnosis of CIN2+ had a HC-II positive test. For CIN3, HC-II was positive in all cases (100%). Assuming a similar specificity level, the relative sensitivity of the HC-II test was higher when histologically confirmed high grade lesions (CIN2+ or CIN3+) were observed. HC-II test had the best sensitivity when defining cases as CIN2+ or CIN3+ (98.7% and 100%, respectively). When using the ASCUS+ cytological cutoff, the differences in CIN2+ and CIN3+ sensitivity between HC-II test and ThinPrep cytology were statistically not significant. Specificity of the ThinPrep cytology for any low and high grade histological lesions was clearly >95% when cytological diagnosis LSIL+ cutoff was used and nearly 100% when HSIL+ cutoff was used. All these specificity estimates were high compared with HC-II test. The specificity of the ThinPrep cytology decreased with about 10% when ASCUS+ was the cutoff. At cutoff ASCUS+, specificity of HC-II was comparable or only slightly lower than with ThinPrep ASCUS+ cytology with no statistically significant differences.ConclusionsThinPrep smears and hr-HPV DNA detection by HC-II performed very well with regard to identifying high grade lesions. HPV DNA testing is a promising new technology for cervical cancer prevention and can be used for primary screening in conjunction with cervical cytology for women aged 30 years and older.     

Managing atypical squamous cells of undetermined significance in Papanicolaou smears

OBJECTIVE: To assess strategies using repeated conventional Pap smear and human papillomavirus (HPV) DNA testing, alone or in combination, for identifying women with concomitant cervical intraepithelial neoplasia 2 and 3 (CIN 2/3) in women with atypical squamous cells of undetermined significance (ASCUS) in their Pap smears. STUDY DESIGN: A total of 360 women cytologically diagnosed with ASCUS were referred for colposcopy and underwent a repeat Pap smear, a biopsy when necessary and HPV testing using three different modes of detection of high-oncogenic-risk HPV types: 1, first-generation Hybrid Capture test (HC-1) (Digene Diagnostics, Gaithersburg, Maryland); 2, second-generation Hybrid Capture test (HC-2); and 3, polymerase chain reaction (PCR). RESULTS: Nineteen patients (5.3%) had histologic CIN 2/3. The sensitivity and specificity of the repeat Pap smear alone for the detection of CIN 2/3 were 73.7% and 62.9%, respectively, when referring all women with a repeat Pap smear using an ASCUS-positive threshold. The proportion of women referred for colposcopy was 39.0%. When HPV testing for high risk was used for identification of women with histologic CIN 2/3, sensitivity and specificity were, respectively, 68.4% and 85.9% for HC-1, 89.5% and 73.9% for HC-2 and 89.5% and 59.0% for PCR. The rate of referral for colposcopy of these three modes of HPV testing was 16.9%, 29.4% and 44.0%, respectively. The sensitivity and specificity for identification of women with concomitant CIN 2/3 using a combination of repeat cytology showing a low grade squamous intraepithelial lesion or high grade squamous intraepithelial lesion and/or a test positive for high-oncogenic-risk HPV group were, respectively, 94.7% and 73.2% when used in combination with HC-2. The referral rate of women for colposcopy of this combined strategy was 30.4%. CONCLUSION: As compared to the strategy using abnormal repeat Pap smear alone, those using high-risk HPV testing with Hybrid Capture showed statistically significantly higher specificities and lower proportions of women with ASCUS referred for colposcopy. In particular, a promising strategy would be to refer for colposcopy only women with repeat Pap smears showing squamous intraepithelial lesion and/or those positive for high-risk HPV detected by Hybrid Capture testing.     

Usefulness of human papilloma virus testing in the screening of cervical cancer precursor lesions: a retrospective study in 314 cases

OBJECTIVE: To assess the usefulness of human papilloma virus (HPV) typing for predicting pre-malignant and malignant cervical lesions. STUDY DESIGN: 314 women, who underwent colposcopy, biopsies and high and low-risk HPV typing after a confirmed abnormal routine Pap test were studied. HPV-DNAs were typed by using PCR technique. RESULTS: We found a significant increasing rate of high-risk-HPV by the increasing severity of histology, ranging from 40% in negative cases to 86.9% in those with CIN3 lesions. The positive predictive value of high-risk-HPV ranged from 13.3% in patients with atypical squamous cells of undetermined significance (ASCUS) to 29.4% in those with HSIL. By contrast, negative predictive value was 96% in patients with ASCUS, 97.2% in low-grade squamous intraepithelial lesions (LSIL), and 71.4% in high-grade squamous intraepithelial lesions (HSIL). Sensitivity and specificity for detecting CIN2 or CIN3 was 86.0% and 41.3%, respectively. CONCLUSIONS: The high negative predictive value of high-risk HPV testing suggests that HPV negativity could be used for predicting the absence of important cervical lesions, and therefore avoiding unnecessary colposcopy in ASCUS and LSIL cases.     

Cytology versus visual inspection with acetic acid among women treated previously with cryotherapy in a low-resource setting

Objective

To compare visual inspection with acetic acid (VIA) with conventional cervical cytology as a follow-up cervical cancer screening method in women who had been treated previously with cryotherapy.

Methods

Salvadoran women screened with VIA and treated with cryotherapy within 3 years were eligible to participate. Study participants were rescreened with VIA, Pap smear, colposcopy, 4-quandrant biopsy, and endocervical curettage.

Results

Of 147 women enrolled in the study, post-cryotherapy VIA was positive in 39 women (26.5%; 95% CI, 19.6%-34.4%). Of these 39, 1 woman had CIN 1 or higher on biopsy. Post-cryotherapy Pap smear was positive (ASCUS or higher) in 6 women (4.1%; 95% CI, 1.5%-8.7%). Of these 6, 2 women had CIN 1 or higher on biopsy. Post-cryotherapy specificity was significantly higher for Pap compared with VIA (95.8% [138/144]; 95% CI, 91.2%-98.5% vs 73.6% [106/144]; 95% CI, 65.6%-80.6%; P < 0.001).

Conclusion

As the single-visit approach for cervical cancer screening gains popularity, more women will have been treated with cryotherapy. Appropriate follow-up screening is therefore vital. Cytology may be a more suitable screening method than VIA in low-resource settings for women treated previously with cryotherapy.     

Adjunctive testing for cervical cancer in low resource settings with visual inspection, HPV, and the Pap smear.

OBJECTIVE: To test whether the performance of visual inspection using acetic acid (VIA) could be improved through adjunctive testing and to determine whether the combination of visual inspection of the cervix and HPV testing could prove useful for identifying those at highest risk of cervical precancer. METHODS: Between October 1995 and August 1997, 2199 women willing to be screened for cervical cancer in peri-urban clinics in Harare, Zimbabwe received VIA, Pap smear and HPV as screening tests. The presence or absence of (pre)cancer was confirmed via colposcopy with biopsy as indicated for >97% of all women. Computerized simulations of sequential testing scenarios provided estimates of the joint (net) test qualities of different paired combinations of the three tests and allowed for comparisons with the individual test qualities. RESULTS: Using HGSIL/CIN II-III as the reference threshold of disease, the net sensitivity and specificity of VIA and HPV when used sequentially were 63.6 and 81.9%, respectively, compared to 43.3 and 91%, respectively, when Pap smears were followed by HPV testing. VIA followed by the Pap smear yielded a net sensitivity of 37.5% and net specificity of 94.3%. CONCLUSIONS: For programs with limited resources but with the capacity for HPV testing, sequential testing involving the use of VIA followed by HPV could yield fewer false positives than the use of VIA alone at a cost of relatively few additional false negatives.     

Aided visual inspection with acetic acid (VIA) and HPV detection as optional screening tools for cervical cancer and its precursor lesions

PURPOSE OF INVESTIGATION: To assess the contribution of visual inspection with acetic acid (VIA) and Hybrid Capture II (HCII) as adjunct methods to the Pap test in detecting cervical neoplasia. SUBJECTS AND METHODS: This was a cross-sectional study with 809 women who consecutively attended gynecological consultations at Campinas University, Brazil, from January 2002 to July 2003. Pap test, HCII, VIA, and colposcopy were offered to all patients. Performance of tests (alone or in combination) in detecting histologically confirmed lesions was evaluated. RESULTS: Of the 40 patients with CIN, 69% had CIN1, 26% CIN2 or CIN3 and one patient had invasive carcinoma. VIA had the best performance in detecting CIN, yielding 72% sensitivity and 91% specificity. Considering only CIN2 or worse as significant lesions, HCII had the best sensitivity (73%), while the Pap test was the most specific (93%). Combining the three exams, 92% of the CIN1 or worse were detected. When CIN1 was excluded from the analysis, Pap smear plus HCII delivered 82% sensitivity and 79% specificity. However, this combination yielded a very low (5%) PPV. CONCLUSION: VIA and HCII contributed to the screening of cervical neoplasia in a group of Brazilian women, but the cost-effectiveness of conjoint screening modalities is still debatable.     

Triage of atypical squamous cells of undetermined significance with hybrid capture II: colposcopy and histologic human papillomavirus correlation

OBJECTIVE: To estimate the effectiveness of Hybrid Capture II to predict high-grade cervical intraepithelial neoplasia (CIN) from a cytological cervical sample. Evidence of high-risk human papillomavirus (HPV) was also determined from biopsy samples using the polymerase chain reaction (PCR) for women referred with atypical squamous cells of undetermined significance (ASCUS) Papanicolaou smears. METHODS: We screened 8170 women with Papanicolaou smears, of whom 278 (3.4%) returned ASCUS. All ASCUS cases underwent colposcopy and Hybrid Capture II testing. High-grade CIN biopsy specimens were tested for high-risk HPV by PCR. RESULTS: Nearly 30% of ASCUS cases had CIN biopsy results (11.9% showing CIN II or CIN III and 17.6% showing CIN I). Hybrid Capture II positive rates were 93.3% for cases with CIN III, 72.2% for CIN II, and 51.0% for CIN I (P <.001). ASCUS-Premalignant Process Favored cases showed a 28.1% high-grade biopsy rate and a 100% Hybrid Capture II positive rate. For ASCUS-Undefined and ASCUS-Reactive Process Favored cases, Hybrid Capture II returned positive in 90.9% of CIN III and 61.5% of CIN II cases (P <.001). Sixty-nine of 178 (38.8%) patients with no evidence of CIN tested positive for Hybrid Capture II. Human papillomavirus deoxyribonucleic acid (DNA) high-risk subtypes were detected by PCR in the tissue of all high-grade CIN cases with negative Hybrid Capture II results. CONCLUSION: Hybrid Capture II returned negative in 25% of cases with biopsy-proven high-grade CIN with associated high-risk HPV DNA by PCR (non-Premalignant ASCUS subset), and positive in 39.3% of cases with normal results; this limits its clinical utility.     

Trends in cervical cancer screening in developing countries

Developing countries suffer the highest burden of cervical cancers but have the lowest resources. Effective cervical cytology screening programme, along with a network of diagnostic and therapeutic colposcopy centres, like developed countries, is almost impossible to be reproduced in developing countries. Visual inspection methods [e.g., Visual inspection with Lugol’s iodine (VILI) and Visual Inspection with Acetic Acid (VIA)] which are cheaper, require less expertise and have the advantage of possible treatment in one setting have been shown to be effective alternatives. The sensitivity to detect CIN2+, by VIA and VILI, have been shown to be 80% and 91% respectively, with a specificity rate of 92% and 85% respectively. Screening by human papillomavirus (HPV) testing has high sensitivity (96.4%) but low specificity (94.1%) to detect CIN2+, when compared to Pap Smear (sensitivity, 55.4% and specificity, 96.8%). A single lifetime HPV testing in a large unscreened population has been shown to significantly reduce cervical cancer incidence and mortality when compared to cervical cytology, VIA or no screening. HPV testing of self-collected vaginal specimens also helps to overcome religious and socio-cultural barriers towards pelvic examination amongst women in developing countries. Current HPV testing methods are expensive, skill/infrastructure demanding and takes time to produce results. A cheaper HPV test, called careHPV™, which is able to provide results within 2.5 h and requires minimal skill/infrastructure to operate, was designed for use in developing countries. One stop screen and treat facilities using VIA or rapid HPV testing, and cryotherapy, can overcome non-compliance to follow-up which is a major issue in developing countries. Cure rates of 81.4% for CIN1, 71.4% for CIN2 and 68.0% for CIN3 at 6 mo after treatment have been reported. Incorporating telemedicine with cervicography of VIA or VILI or even telecolposcopy, has great potential in cervical cancer screening, especially in countries with vast geographical areas.     

宫颈巴氏涂片与LCT在低收入妇女妇科普查中的应用

目的探讨宫颈巴氏涂片与液基细胞学（LCT）在低收入已婚妇女宫颈癌筛查中的应用价值。方法2008年1月至6月上海市浦东新区妇幼保健院对所在社区6416例低收入已婚妇女（低收入组）采用宫颈巴氏涂片进行了宫颈癌筛查,其中322例同期行LCT,并与同期来上海市浦东新区妇幼保健院做宫颈癌筛查行LCT的294名妇女进行对照（对照组）。结果①宫颈刮片巴氏异常者（≥Ⅱb级）低收入组中22例（0．34％）,其中Ⅱb级12例（0．19％）,Ⅲ级10例（0．16％）,无Ⅳ级及Ⅴ级。15例（Ⅱb5例,其余Ⅲ级）行阴道镜下活检,病理结果CIN8例,其中CIN12例,CIN2和CIN3各3例;②低收入组同期行LCT的322例妇女中,细胞学≥ASCUS共41／322例（12．73％）,其中ASCUS15例,HSIL 1例,行阴道镜下活检病理结果CIN5例（CIN1和CIN2各2例,CIN31例）;HSIL1例为子宫颈鳞状细胞癌。对照组：细胞学≥ASCUS 22／294例（7．48％）。其中ASCUS 11例行阴道镜下活检。病理结果仅CIN 21例;2例LSIL;1例为CIN2。两组AGC各1例经阴道镜下活检均无异常;③低收入组中322例行宫颈刮片和LCT做自身对照：315例巴氏均为Ⅰ级,LCT正常;巴氏Ⅱb级2例,LCT均为ASCUS,病理分别为CIN1和CIN2;巴氏Ⅲ级3例,LCT检查,其中2例为ASCUS,阴道镜活检仅1例病理为CIN2。结论宫颈细胞学是筛查宫颈病变的有效手段,巴氏涂片法在基层对低收入人群仍可为主要筛查方法。有条件者可采用LCT,以提高宫颈疾病筛查的敏感性。     

Prospective follow-up suggests similar risk of subsequent cervical intraepithelial neoplasia grade 2 or 3 among women with cervical intraepithelial neoplasia grade 1 or negative colposcopy and directed biopsy

OBJECTIVE: The purpose of this study was to determine the risk of cumulative cervical intraepithelial neoplasia (CIN) grade 2 or 3 according to initial colposcopy and directed biopsy results among women with low-grade squamous intraepithelial lesions (LSIL) or human papillomavirus (HPV) DNA positive atypical squamous cells of undetermined significance (ASCUS). STUDY DESIGN: A 2-year follow-up of 897 cases of LSIL and 1193 cases of HPV DNA positive ASCUS from the ASCUS/LSIL Triage Study was used to simulate American Society for Colposcopy and Cervical Pathology Consensus Conference recommendations. Women with CIN grade 1 or less were followed up for 2 years by semiannual cytologic examination, with universal exit colposcopy. The clinical end point was a cumulative clinical center histologic diagnosis of CIN grade 2 or 3. RESULTS: The cumulative risk of CIN grade 2 or 3 was equivalent for LSIL (27.6%) and HPV positive ASCUS (26.7%). After excluding the women with a diagnosis of CIN grade 2 or 3 at initial colposcopy and directed biopsy (17.9%), the remaining women were at nearly identical risk for subsequent CIN grade 2 or 3 regardless of initial colposcopy result (completely negative colposcopy-11.3%; negative colposcopically directed biopsy-11.7%; and CIN grade 1 biopsy-13.0%). CONCLUSION: LSIL and HPV positive ASCUS are clinically equivalent. Initial colposcopic detection of obviously prevalent CIN grade 2 or 3 reduces risk. However, for the remaining women who have CIN grade 1 or less on colposcopy and directed biopsy, the risk for subsequent CIN grade 2 or 3 (whether missed, prevalent, or truly incident) is approximately 12% over 2 years. This risk does not vary meaningfully by initial distinction of histologic CIN grade 1 from negative colposcopy and biopsy.     

Implications regarding atypical squamous cells of undetermined significance among women residing in a US–Mexico border city

We conducted a study of Mexican American women living in a US-Mexico border city who attended a gynecology clinic for Papanicolaou (Pap) smear. The objective of this study was to describe the cytologic outcomes of women who had atypical squamous cells of undetermined significance (ASCUS) diagnosis after a Pap smear and to observe any changes during follow-up colposcopy. A total of 852 abnormal Pap smear were identified through a computer search for a 6-month period. Histology data were available for 317 cases. Benign findings were observed in 45.4% of cervical biopsies. A clinically significant diagnosis was reported in the remaining tissue sample. The diagnosis report was either single or combined and recorded as follows: human papilloma virus 46.3%, cervical intraepithelial neoplasia (CIN) 1, 23.6%; CIN 2, 5.6%; and CIN 3, 1.5%. There was one case of invasive cervical cancer. Overall, the incidence rate of ASCUS was 5%. However, we found that a significant proportion of this population had CIN 1 through CIN 3. Furthermore, this population has traditionally been noncompliant and routinely failed to attend follow-up appointments. Based on these results, the clinician should not ignore an initial abnormal Pap smear. Therefore, it is not unreasonable to perform colposcopy in Mexican American patients with a first time diagnosis of ASCUS on routine Pap smear.     

Human papillomavirus DNA detection and histological findings in women referred for atypical glandular cells or adenocarcinoma in situ in their Pap smears

OBJECTIVE: To evaluate the association between high-risk human papillomavirus (HPV) DNA detection and histological diagnosis in women referred for atypical glandular cells (AGC) or adenocarcinoma in situ (AIS) at Pap smear. METHODS: In this cross-sectional study, 146 women referred for AGC (124), AGC with high-grade squamous intraepithelial lesion (HSIL) (15), or AIS (7) were tested for HPV DNA using Hybrid Capture II (HC II). All women underwent colposcopic examination, and cervical biopsy was performed for 95 patients. Fifty-one women referred due to AGC with normal colposcopy and normal second Pap smear were scheduled for control visits every 4 months. RESULTS: The overall prevalence of HPV DNA was 38%. HPV DNA was detected in 93% of the women with HSIL associated with AGC and in 71% of women with AIS Pap smear, being significantly higher when compared with the prevalence (29%) in women with AGC alone. Forty-five women (30.8%) had clinically significant histological lesions (CIN 2 or worse). High-risk HPV DNA was detected in only 16% of the women without significant abnormalities in biopsy, in contrast to 96% of those who had CIN 2 or CIN 3 and 75% of women with AIS. Eighty-five percent of women with invasive cervical carcinoma (squamous or adenocarcinoma) tested positive for HPV DNA. HPV DNA detection was significantly associated with histological diagnosis of CIN 2 or worse, with an odds ratio (OR) = 51.8 (95% CI 14.3-199.9). CONCLUSION: HPV DNA detection was strongly associated with the severity of cervical lesion (CIN 2 or worse) in women referred for AGC or AIS in their Pap smear. These data implicate the use of HPV testing in triage of women with AGC Pap smears.     

A Study of Cervical Intraepithelial Neoplasia in Pregnancy

Objective

To find the incidence of human papillomavirus (HPV) infection and cervical intraepithelial neoplasia (CIN) in pregnant women and compare Pap smear with the HPV DNA test in detecting HPV infection.

Materials and Methods

Hundred antenatal women, irrespective of gestational age, were enrolled as subjects in this prospective pilot study for blood investigations, wet mount examination of cervical discharge, Pap smear, and high-risk HPV DNA detection of cervical scrape by PCR. Women showing abnormality in Pap smear and/or those who were high-risk HPV DNA positive were subjected to colposcopy.

Results

The incidence of HPV-positive pregnant women was 18 %. Koilocytosis on Pap smear was observed in six women. Three high-risk HPV DNA-positive women showed changes consistent with CIN 1 on colposcopy.

Conclusions

The HPV DNA test is the most sensitive and reliable in detecting HPV infection as compared to Pap smear, but considering the cost of PCR, Pap smear screening of all antenatal women was recommended.     

Postcolposcopy management strategies for women referred with low-grade squamous intraepithelial lesions or human papillomavirus DNA-positive atypical squamous cells of undetermined significance: a two-year prospective study

OBJECTIVE: This study was undertaken to compare postcolposcopy management strategies for women referred for low-grade squamous intraepithelial lesions (LSIL) or oncogenic human papillomavirus (HPV) DNA-positive atypical squamous cells of undetermined significance (ASCUS), with cervical intraepithelial neoplasia (CIN) grade 1 or less found at initial colposcopy. STUDY DESIGN: A 2-year prospective follow-up of 1539 women was designed to assess the percentage sensitivity of different postcolposcopy management strategies to detect subsequent CIN grade 2 or 3 and percentage referral to repeat colposcopy. RESULTS: HPV testing at 12 months was sensitive (92.2%) for detection of CIN grade 2 or 3 with a referral rate to repeat colposcopy of 55.0%. Repeat semiannual cytology with referral to colposcopy at an ASCUS threshold demonstrated similar sensitivity (88.0%) but with a higher rate of referral to colposcopy (63.6%). Combining cytology and HPV testing did not increase sensitivity and hurt specificity. Baseline viral load and colposcopic impression were not helpful. CONCLUSION: The most efficient test for identifying women with CIN grade 2 or 3 after colposcopy might be an HPV test alone at 12 months.     

The significance of ASCUS cytology in HIV-positive women.

OBJECTIVE: The aim of this study was to determine the incidence and severity of dysplasia associated with a cytologic diagnosis of atypical cells of undetermined significance (ASCUS) in women infected with the human immunodeficiency virus (HIV). METHODS: A cross-sectional analysis of cervical cytology, colposcopic impression, and cervical biopsy results was performed on 261 HIV-positive women diagnosed with ASCUS. The prevalence and grade of histologically documented cervical intraepithelial neoplasia (CIN) was determined. Patients with CD4 counts above and below 200 cells/mm(3) were compared using chi(2) analysis to determine any effect of worsening immunosuppression on the rates of associated dysplasia. RESULTS: Seven hundred sixty-one Pap smears were performed during the study period. Two hundred nine (27%) were diagnosed as ASCUS. All patients (pts) received colposcopic evaluation. The incidence of human papilloma virus (HPV) effect, low-grade CIN (I), and high-grade CIN (II, III, and carcinoma in situ) documented by cervical biopsy, cervical conization or endocervical curettings was 40, 17, and 15%, respectively. No cases of invasive cancer were found. These results are similar to those of previous cytohistologic studies of ASCUS in HIV-untested populations. There was no significant difference in frequency or severity of CIN in pts with severe immunosuppression (P = 0.4). CONCLUSION: A cytologic diagnosis of ASCUS in HIV-positive women identifies a group at significant risk for histologic abnormalities. The majority of pts will be diagnosed with HPV or low-grade CIN. HIV infection and severe immunosuppression do not appear to increase the frequency or severity of CIN associated with ASCUS. Given the 32% risk of associated CIN, all HIV-positive women with ASCUS cytology should undergo colposcopic evaluation.