Detection of HPV by PCR—A Novel Step in the Prevention of Cancer Cervix

Objectives

(1) To compare the efficacy of Pap smear and HPV PCR for detection of CIN; and (2) To study the distribution of HPV genotypes.

Methods

One hundred women presenting at the female Outpatient Department with unhealthy cervices were subjected to a detailed history, clinical examination, Pap smear, HPV DNA PCR test, and colposcopic-directed biopsy (where indicated).

Results

This study has shown that there is a strong association of HPV infection with higher grades of CIN (100 % in patients with CIN 2, CIN 3, and CIS). The detection of CIN by HPV PCR was more accurate than by Pap smear. The most prevalent HPV genotype found in our study was HPV 16.

Conclusion

The advent of HPV testing has opened the doors for more accurate cervical cancer surveillance strategies than Pap smear. Early detection and treatment of CIN will considerably reduce the incidence of cervical cancer.     

Complementary Procedures in Cervical Cancer Screening in Low Resource Settings

Objective

To evaluate the efficacy of pap smear, HPV DNA testing and colposcopy and to determine the approach for cervical cancer screening in low resource settings.

Methods

Eight hundred non pregnant married women above 30 years of age were studied and subjected to pap smear examination. Hysterectomised women were excluded from the study. Selected patients were followed by HPV DNA testing by Hybrid Capture II method, colposcopy and biopsy. Sensitivity, specificity, Positive predictive value (PPV), Negative predictive value (NPV), diagnostic accuracy and kappa value (k) were calculated for each screening test.

Result

Out of eight hundred women with mean age 36.5 ± 5.94 years undergoing pap smear, ASCUS was found in 66(8.25%), ASC-H in 2(0.25%), LSIL in 48(6%), HSIL in 8(1%), inflammatory in 540(67.5%). Out of 260 women who underwent HPV DNA testing, 120 (46.15%) had abnormal cytology and/or positive HPV DNA test (Group I, n = 120) and 140(53.8%) had dual negative results (Group II, n = 140) HPV DNA test was found positive in 64 women (53.3%) in Group I. Sensitivity and specificity of pap smear was 69.2 and 63.72% while for HPV DNA testing was 92.3 and 84% respectively. PPV and NPV of pap smear, HPV DNA testing and colposcopy was 18, 40, 76.4% and 94.7, 98.9, 100% respectively. Diagnostic accuracy of pap smear (k = 0.14), HPV DNA test (k = 0.70) and colposcopy (k = 0.81) was 64.29, 84.9, and 96.8% respectively. Combining pap smear &; HPV DNA testing (k = 0.25) increased the sensitivity and NPV to 100%.

Conclusion

Sensitivity and diagnostic accuracy of HPV DNA test is more than that of pap smear and the test is not influenced by inflammatory conditions of vagina. In low resource settings, women with ASCUS and LSIL on cervical cytology should be subjected to HPV DNA test and only if found positive should be referred for colposcopy thereby reducing colposcopy referrals. Women with HSIL should be directly subjected to colposcopy guided biopsy. Using this approach, most of the preinvasive cervical lesion will be detected but few cases will still be missed among inflammatory smears, if HPV DNA testing is not supplemented.     

Perinatal outcomes of pregnant women with cervical intraepithelial neoplasia

Objective

To investigate the perinatal outcomes of pregnant women with cervical intraepithelial neoplasia (CIN).

Method

The women in this retrospective case–control study were recruited from Beijing Obstetrics and Gynecology Hospital from August 1, 2007 to February 28, 2010. All the cases were 13–32 gestational weeks, who were diagnosed by colposcopy conducted cervical biopsy. A total of 108 cases were followed-up to the day of delivery.

Results

(1) Complications of colposcopy conducted cervical biopsy: there were two cases of pregnant women, who suffered cervical local compression after undergoing colposcopy conducted cervical biopsy, as the bleeding could not be stopped, the wound was treated by local suture. The incidence of such event was 1.8 % (2/108), without any colposcopy and biopsy-related adverse event. (2) Cesarean section rate was 63.6 % (56/88) in CIN, which was higher than 30.0 % (6/20) in cervicitis, and the cesarean section rate increased as CIN grades elevated, and gestational weeks of delivery advanced.(P < 0.05). (3) We did not detect significant difference for the incidence of polyhydramnios, premature rupture of fetal membranes, placental abruption, cervical laceration and postpartum hemorrhage, low birth weight infants, amniotic fluid II–III degree, neonatal deformity and neonatal asphyxia between pregnant women with CIN and cervicitis (P > 0.05); however, the incidence of oligohydramnios and premature infants in pregnant women with CIN group were higher than that in cervicitis group (P = 0.007; P = 0.020). (4) Vaginal delivery and HR–HPV infection did not increase the incidence of perinatal complication; the volume of postpartum hemorrhage within 2 h after birth in vaginal delivery was less than in cesearean section for pregnancies with CIN (P = 0.000).

Conclusion

Pregnant women with CIN can be diagnosed by colposcopy conducted cervical biopsy, and they should be carefully monitored oligohydramnios and preterm during pregnancy. Pregnant women with CIN during pregnancy, excluding other obstetric operation indications may choose vaginal delivery first.     

Detection and genotyping of cervical HPV with simultaneous cervical cytology in Turkish women: a hospital-based study

Purpose

To investigate the prevalence of cervical human papilloma virus (HPV) with genotyping and simultaneous cervical cytology among Turkish women in a university hospital. A review of literature was done as well to summarize the results of similar Turkish studies based on hospital data.

Methods

Women who were subjected to cervical HPV-DNA testing with simultaneous cervical Pap test were included. Seeplex HPV 18-plex Genotyping Test was used for HPV detection and typing. Liquid-based cytology was used for Pap test and Bethesda system was used for results.

Results

Study group included 890 patients with a mean age of 39.5?years. The prevalence of any HPV was 25.7% while high-risk HPV was positive in 23.0%. There were no significant differences in HPV prevalence between younger and older women. Among HPV-positive women, 89.5% had at least one type of high-risk HPV. Most common HPV was type 16 followed by type 31 and 51. Abnormal cervical cytology rate was 11.6%. Rate of HPV positivity was significantly higher in women with abnormal cervical cytology compared to women with normal cytology (54.4 vs. 22.0%).

Conclusions

Cervical HPV infection is a serious and gradually growing problem for Turkish women according to hospital-based data. This may be associated with low age at marriage and more sensitive HPV detection methods.     

Primary high-risk HPV screening for cervical cancer in post-menopausal women

Objective

The present study was conducted to examine the value of screening for high-risk HPV in post-menopausal women.

Methods

A cohort of post-menopausal women (n = 2113), age range 55-76 years, from Uppsala County, Sweden, were offered testing for both high-risk HPV and a Pap smear in the gynaecological screening during 2008-2010. For the HPV test the cervical smear sample was applied to a filter paper matrix, an indicating FTA elute card and HPV typing performed using a real-time PCR assay. Histological verified CIN2+ lesion was used as an end-point measurement.

Results

High-risk HPV were found in 6.2% (95% CI 5.2-7.3%) of the women (n = 130) and 22% (95% CI 14-32%) (n = 17) of these had CIN2+ lesions based on histology. The Pap smear taken in conjunction with the HPV test was abnormal in 9.7% (95% CI 5.7-16.3%) (n = 12) of HPV positive women. Among HPV positive women with an abnormal Pap smear, the frequency of histology verified CIN2+ lesions was 67% (95% CI 38-86%) (n = 8), as compared to 14% (95% CI 7-24%) (n = 9) in HPV positive women with a normal smear. The prevalence of HPV16 in CIN2+ lesions (29%, 95% CI 22-37%) in post-menopausal women was less than half of previous estimates in pre-menopausal women from this population.

Conclusions

Most histological CIN2+ lesions in post-menopausal women are not recognized by a single Pap smear. A large fraction of pre-invasive cervical cancer cases in post-menopausal women result from infections by HPV types not included in the present vaccine formulas.     

Human papillomavirus DNA and mRNA positivity of the anal canal in women with lower genital tract HPV lesions: predictors and clinical implications

Objective

Women with HPV related pathology of the lower genital tract are at higher risk for AIN and anal cancer than the general population. A strategy to identify anal disease in these women has not been formulated. The aim of this study is to examine the feasibility of HPV related biomarker testing on anal smears, to identify the risk factors for anal HPV positivity and to provide information of the clinical implications of anal HPV infection in this population.

Methods

In women referred for colposcopy because of HPV related pathology of the lower genital tract (cervical cancer, CIN, VIN, warts) a detailed questionnaire, an anal smear and a cervical smear were taken. On each sample morphological cytology, flow cytometric evaluation of E6&7 mRNA, and HPV DNA detection and typing were performed. Women with a positive anal result were referred for high resolution anoscopy.

Results

So far 235 women have been included (mean age 34.3). HPV DNA, high-risk HPV DNA, high-risk mRNA was detected in 45%, 31% and 8% of the anal smears and in 56%, 39% and 25% of the cervical smears respectively. Absolute or partial concordance of the types between the cervix and the anus was seen in 74%. Positivity for mRNA was significantly lower in the anus than the cervix (8% vs 25%). Logistic regression analysis revealed risk factors for the presence of anal HPV DNA (> 3 lifetime sexual partners and presence of cervical HPV DNA), hr HPV DNA (presence of cervical hr HPV DNA), and hr mRNA (presence of cervical hr mRNA). Twelve months after LLETZ 53% of women were cervical HPV negative, but 25% of those were still HPV positive in the anus.

Conclusions

HPV infection of the anus is common in this group and is interlinked with the cervical infection. Anal HPV E6&7 mRNA expression is less common than in the cervix. Possible clinical implications of anal infection could be the development of AIN and recurrence of CIN after treatment due to cervical reinfection from the anal reservoir. The use of HPV biomarkers is feasible in anal smears, although especially DNA testing as triage method for referral to anoscopy is probably inappropriate due to high positivity rate.     

Interest of Human Papillomavirus DNA quantification and genotyping in paired cervical and urine samples to detect cervical lesions

Background

Cervical cancer is caused by persistent infection with high-risk human papillomavirus (HR-HPV). Conventional human papillomavirus (HPV) testing requires cervical sampling. However, vaginal and urine self-sampling methods are more acceptable for patients and result in increased participation when they are available in screening programs. In this context, we have developed a non-invasive screening method via the detection of HPV DNA in urine samples.

Purpose

To compare HPV viral loads and genotypes in paired cervical and urine samples, and to assess correlation between virological and cytological results in women seeking gynecological consultation.

Methods

Paired urine and cervical specimens were collected and analyzed from 230 of 245 women participating in the previously described prospective PapU study. HPV DNA detection and quantification were performed using a real-time PCR method with short fragment PCR primers. Genotyping was carried out using the INNO-LiPA HPV genotyping assay.

Results

The prevalence of HPV in the 230 paired urine and cervical smear samples was 42 and 49 %, respectively. Overall agreement for HPV positivity and negativity between the paired samples was 90 % (κ = 0.80). High HPV viral load in both cervical and urine samples was associated with cytological abnormalities. HPV-positive women were mostly infected with HR-HPV types. The agreement between high- and low-risk HPV (LR-HPV) detection in both samples was 97 % (κ = 0.95 for HR-HPV and κ = 0.97 for LR-HPV).

Conclusions

High concordance rates for HPV-DNA quantification and high/low-risk HPV genotyping in paired urine/cervical samples suggest that urinary HPV DNA testing could be useful for cervical lesion screening.     

Clinical management of cervical intraepithelial neoplasia in pregnant and postpartum women

Objective

To evaluate the clinical management of cervical intraepithelial neoplasia (CIN) and cervical microinvasive squamous cell carcinoma in pregnant and postpartum women.

Methods

This prospective study enrolled 27,230 pregnant women undergoing routine gestational examinations between August 1, 2007 and July 31, 2010 in the Beijing Obstetrics and Gynecology Hospital, Capital Medical University. Colposcopy and cervical biopsy were performed for patients with abnormal Thin Prep^® Papanicolaou test (TCT) results. Periodic colposcopy was performed every 8–12 weeks and cervical biopsy was performed if progression was suspected. Cervical cold knife conization was recommended to patients diagnosed with CINIII or microinvasive cervical carcinoma 6–12 weeks after delivery.

Results

A total of 2,260 patients had abnormal TCT results (8.12 %). Colposcopy and cervical biopsy were performed for 369 patients. Fifteen patients had microinvasive squamous cell carcinoma, 116 patients had cervicitis, and the number of CIN patients with histological grades I, II, and III were 124, 49, and 65, respectively. Tumor progression during pregnancy was found in 253 patients (CINI or above). Prognosis varied depending on the highest grade of pathological diagnosis results during pregnancy or initial pathological diagnosis results performed 6–12 weeks after delivery by cervical biopsy under colposcopy. Treatment and follow-up were carried out according to diagnoses, state of progression, and reversion (if any).

Conclusion

These findings underline a need for cervical lesion screening for all women during pregnancy, and colposcopy should be performed for pregnant women who have abnormal TCT results. Appropriate treatment and follow-up were recommended according to different diagnosis of CIN.     

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.     

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.     

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.     

Triaging Pap cytology negative, HPV positive cervical cancer screening results with p16/Ki-67 Dual-stained cytology

Objective

Testing for human papillomavirus (HPV) has been shown to increase the sensitivity and negative predictive value for detection of high-grade cervical intraepithelial neoplasia (CIN2+), either when used in conjunction with Pap cytology testing or alone. However, there is no satisfying clinical management algorithm for women testing Pap negative/HPV positive. We therefore evaluated the clinical utility of a novel dual biomarker-based approach (p16/Ki-67 Dual-stained cytology) for the identification of CIN2+ in women with Pap negative/HPV positive screening results, without the need to refer all women to immediate colposcopy.

Methods

All women aged ≥ 30 enrolled during 2007/2008 into a regional prospective Pap/HPV co-testing screening pilot project and tested Pap negative, but positive for HPV (n = 425) were included in the analysis. p16/Ki-67 Dual-stained cytology was performed from residual cellular material available from the liquid-based cytology vial collected during the initial Pap/HPV co-testing screening visit. Results were correlated to the presence of CIN2+ confirmed during preliminary follow-up.

Results

p16/Ki-67 Dual-stained cytology tested positive at baseline in 108 out of 425 (25.4%) Pap negative/HPV positive cases. Sensitivity of Dual-stain testing for the detection of biopsy-confirmed CIN2+ during preliminary follow-up within the group of Pap negative/HPV positive women was 91.9% for CIN2+ (34/37 cases), and 96.4% for CIN3+ (27/28 cases). Specificity was 82.1% for CIN2+ on biopsy, and 76.9% for CIN3+, respectively.

Conclusions

Triaging Pap negative/HPV positive screening test results with p16/Ki-67 Dual-stained cytology may identify women with a high probability of underlying CIN2+ and may efficiently complement HPV-based screening programs to prevent cervical cancer.     

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.     

Three-step versus “see-and-treat” approach in women with high-grade squamous intraepithelial lesions in a low-resource country

Objective

To investigate the frequency of cervical intraepithelial neoplasia (CIN) 2 or greater in women with high-grade squamous intraepithelial lesion (HSIL), and to evaluate whether colposcopically-directed biopsy is a necessary procedure for managing HSIL in a low-resource country.

Methods

A retrospective review was undertaken of women with HSIL on a Pap smear.

Results

Of 348 women who had undergone colposcopically-directed biopsies and loop electrosurgical excisional procedure (LEEP), 321 (92.2%) had CIN 2 or greater. Of these, 279 were diagnosed with CIN 2 or greater on biopsy as were 264 on LEEP. The lesions in women who had CIN 2, satisfactory colposcopy, and more biopsies were more likely to be completely excised by biopsy. The mean length of time between the initial Pap smear and LEEP was significantly longer than between the initial Pap smear and biopsy.

Conclusion

Women with HSIL can be effectively managed using the see-and-treat approach in a low-resource country owing to the frequency of CIN 2 or greater.     

Type-specific human papillomavirus DNA testing with the genotyping array: a comparison of cervical and vaginal sampling

Objective

To compare the detection and typing of human papillomavirus (HPV) between vaginal and cervical specimens by using polymerase chain reaction (PCR)-based reverse-blot genotyping arrays.

Study design

Two hundred and fifty-two women were referred to colposcopy clinics because of suspicious or positive results in a community-based cervical cancer-screening program. Genital tract cells were sampled from the cervix and self-collected from the vagina and tested with the HPV Blot kit.

Results

The HPV Blot kit identified HPV infection in 24.7% of vaginal specimens and in 30.2% of cervical collections. Cervical sampling detected significantly more infections compared to vaginal sampling only for HPV type 52; cervical sampling also detected significantly more high-risk HPV infection overall. The sensitivities of detecting histology ≥cervical intraepithelial neoplasia (CIN) grade 3 using the HPV Blot in vaginal and cervical specimens were 75.0% (95% CI, 47.6-92.7%) and 87.5% (95% CI, 61.6-98.4%), respectively (P = 0.48). Both sampling methods were thus statistically effective at detecting high-grade lesions and cervical cancer (P < 0.0001).

Conclusions

The HPV Blot yielded similar results for both vaginal sampling and cervical sampling in the detection of CIN grade 3 or worse. These findings indicate that self-sampling for HPV testing is a viable cervical cancer screening option.     

Triaging HPV-positive women with p16/Ki-67 dual-stained cytology: Results from a sub-study nested into the ATHENA trial

Objectives

In addition to genotyping for HPV16/18, dual-immunostaining for p16/Ki-67 has shown promise as a triage of HPV-positive women. We assessed the performance of p16/Ki-67 dual-stained cytology for triaging HPV-positive women undergoing primary HPV screening.

Conventional Pap Smear Screening in HIV Seropositive Women in South India

Objectives

To assess the prevalence of Pap smear abnormalities and to characterize the associated risk factors in HIV seropositive women.

Material and methods

We conducted a cross-sectional study on 252 HIV seropositive women in and around Krishna district, Andhra Pradesh, India by screening them for cervical cytological abnormalities by means of conventional Pap smear screening and the abnormalities reported as per modified Bethesda system.

Results

The prevalence of Pap smear abnormalities in HIV seropositive women was found to be 7.17 % which was a twofold increased risk as compared to the general population. On analysis of the risk factors like younger age for abnormal pap smears, mean CD4 count, duration of disease, and ART/HAART therapy the difference between the two groups of HIV seropositive women with normal pap smears and seropositive women with abnormal pap smears was found to be not statistically significant.

Conclusion

HIV/AIDS is associated with a twofold increased risk for cervical cytological abnormalities, and hence the need for periodic pap smear screening in this high risk group to reduce the global burden of cervical cancer.     

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.     

The feasibilities of TruScreen for primary cervical cancer screening: a self-controlled study

Objective

Screening programs based on cytology testing led to the incidence reduction of cervical cancer mortality of about 70–80 % in industrialized countries. However, these favorable results have not been replicated in developing areas. Thus, we aim to evaluate the efficacy of TruScreen (Polartechnics, Sydney, Australia) in detecting of precancerous lesions in comparison with cervical cytology test.

Methods

A total of 181 outpatients were screened by TruScreen using the pathological results as the gold standard. The medical records of cytological smear within 6 weeks were obtained from 169 of these participants. The reliability and yield of TruScreen and cytological smear were assessed. The screening results of TruScreen were compared with those obtained from the conventional smear.

Results

The sensitivities for histologically confirmed cervical intraepithelial neoplasia (CIN) lesions by TruScreen and Pap, were 67.4 % (95 % CI 53.4–81.5) and 87.9 % (95 % CI 76.7–99.0), respectively. The specificities for histologically confirmed CIN lesions by TruScreen and Pap, were 68.1 % (95 % CI 60.3–75.9) and 74.3 % (95 % CI 70.0–81.4), respectively. In contrast to Pap smear, TruScreen was comparatively efficacious in screening of cervical cancer (χ ² = 0.0133, P = 0.9081).

Conclusion

TruScreen is a potential test for initial cervical screening in developing world regions.     

Cervical cytology with a diagnosis of atypical squamous cells,cannot exclude high-grade squamous intraepithelial lesion (ASC-H): a follow-up study with corresponding histology and significance of predicting dysplasia by human papillomavirus (HPV) DNA testing

Objectives

To evaluate the clinical significance of “atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion” ASC-H by comparing the original cytologic findings with follow-up tissue biopsies, and its association with high-risk HPV.

Methods

A total of 235,518 ThinPrep Pap tests were performed at our institution from January 2008 through December 2010, but only 727 (0.3 %) of these cases were diagnosed as ASC-H.

Results

Of the 309 cases diagnosed as ASC-H on cytology for which follow-up histologic material was available, 120 (38.8 %) were definitively diagnosed as high-grade dysplasia (CIN 2/3) and 75 (24.2 %) showed features of low-grade dysplasia (CIN 1). We observed that the incidence of dysplasia in patients less than 30 years of age was 73.4 % (113/154) and 48.3 % (14/29) in patients greater than 49 years of age (p = 0.001). There were 71 cases for which high-risk HPV DNA testing was conducted. HPV DNA was found to be positive in 41 of the dysplastic cases (CIN 1 = 18 cases and CIN 2/3 = 23) and negative in six of the dysplastic cases (CIN1 = 2 and CIN2/3 = 4).

Conclusion

We conclude that cases diagnosed as ASC-H should be followed-up with caution as they are strongly associated with dysplasia of any grade (63.1 %), especially high-grade dysplasia (38.8 %). Reflex HPV DNA testing is an important predictor of dysplasia with a positive predictive value of 87.2 % in our study.