Cervical cytology by Papanicolaou (Pap) smears is an effective means of screening for cervical premalignant and malignant conditions. Cervical intra-epithelial neoplasia (CIN) and cervical cancer remain important health problems for women worldwide.
To study the role of Pap smear in detecting premalignant and malignant lesions of cervix; and to determine the prevalence of various lesions.
Materials and Methods:
This study is based on 300 patients who attended the out-patient Department of Obstetrics and Gynaecology. Pap smears were prepared from patients presenting with complaints like vaginal discharge, post-coital bleeding, inter-menstrual bleeding, dyspareunia, and pain lower abdomen. After fixation and staining, each smear was carefully examined.
Epithelial cell abnormalities were found in 5% smears, atypical squamous cells of undetermined significance (ASCUS) in 0.3%, squamous intraepithelial lesion (SIL) in 3.4% which includes low grade squamous intraepithelial lesion (LSIL) (2.7%) and high grade squamous intraepithelial lesion (HSIL) 0.7%. Invasive carcinoma was seen in 1.3% cases. Mean age of the patients with diagnosis of LSIL was 32.3 years and for HSIL, it was 40.5 years. The mean age of the patients with invasive carcinoma was 57 years.
Premalignant and malignant lesions of cervix are not uncommon in our set up and can be diagnosed early by Pap smears.
Cervical cancer; cervical intraepithelial neoplasia; papanicolaou smear
High-risk human Papillomavirus infection is a necessary factor for cervical squamous intraepithelial lesions and invasive cervical cancer. In HIV-1-infected women, HPV infection is more prevalent and a higher risk of cervical cancer has been identified. We aimed to calculate the prevalence of infection by HR-HPV, determine the factors associated with this infection and abnormal cytology findings and to describe the history of cervical cancer screening in HIV-1-infected women.
We enrolled 479 HIV-1–infected women from the PISCIS cohort. Each patient underwent a gynecological check-up, PAP smear, HPV AND Hybrid capture, HPV genotyping, and colposcopy and biopsy, if necessary. We applied questionnaires to obtain information on sociodemographic, behavioral, clinical, and cervical screening variables. We present a cross-sectional analysis.
Median age was 42 years. The prevalence of HR-HPV infection was 33.2% and that of high-grade squamous intraepithelial lesions (HSIL) was 3.8%. The most common genotypes were 16(23%), 53(20.3%), and 52(16.2%). The factor associated with HR-HPV infection was age <30 years (odds ratio[OR],2.5; 95%confidence interval[CI],1.1–5.6). The factors associated with the presence of HSIL or low-grade squamous intraepithelial lesions (LSIL) were CD4T-lymphocyte count <200cells/mm3 versus >500cells/mm3 (OR,8.4; 95%CI,3.7–19.2), HIV-1 viral load >10,000copies/mL versus <400copies/mL (OR,2.1; 95%CI,1.0–4.4), and use of oral contraceptives (OR,2.0; 95%CI,1.0–3.9). Sixty percent of HIV-1–infected women had had one Pap smear within the last 2 years.
The high prevalence of HPV infection and cervical lesions in the HIV-1–infected population in Catalonia, as well as the low coverage and frequency of screening in this group, means that better preventive efforts are necessary and should include vaccination against HPV, better accessibility to screening programs, training of health care professionals, and specific health education for HIV-1–infected women.
The purpose of this study was to determine the prevalence and risk factors for cervical squamous intraepithelial lesions (SIL) among women infected with human immunodeficiency virus type 1 (HIV-1) receiving care at the Federal Medical Center Makurdi, Nigeria.
Between March and December 2009, a total of 253 women infected with HIV-1 had cervical smears taken for cytology. HIV-1 RNA viral load and CD4 counts were also measured.
Of the 253 women, cervical SIL were present in 45 (17.8%). However, abnormal cervical cytology was noted in 146 (57.7%). Of those with abnormal cervical cytology, 101 (39.9%) women had atypical squamous cells of undetermined significance, 16 (6.3%) had low-grade SIL, and 29 (11.5%) women had high-grade SIL. The median CD4 lymphocyte count was lower in participants with cervical SIL compared with those without (132 versus 184 cells/mm3; P = 0.03). The median HIV-1 RNA viral load was higher in women with cervical SIL (102,705 versus 64,391 copies/mL; P = 0.02). A CD4 lymphocyte count of <200 cells/mm3 and an HIV-1 RNA viral load of <10,000 copies/mL were found to be significantly associated with cervical SIL.
A high prevalence of cervical SIL was found among HIV-1-infected women in Makurdi, Nigeria. Increased immune suppression and HIV-1 viremia are significantly associated with cervical SIL.
cervical squamous intraepithelial lesions; human immunodeficiency virus; risk factors; immunosuppression; cervical dysplasia; Nigeria
The California Department of Health Services conducted a cervical cancer screening program in 12 counties where local health agencies provided the screening services. A major purpose of the study was to screen women at high risk of cervical cancer and to assure that women with abnormal results on cervical cytology testing obtained appropriate diagnostic workup and treatment. A total of 34,318 women were screened, and 7,811 returned for up to 3 annual rescreening examinations. Final cytologic results were 33,658 normal, 100 unsatisfactory, and 560 abnormal smears. Of the abnormal smears, 484 were indicative of cervical dysplasia, 41 of in situ cervical cancer and 22 of invasive cervical cancer. In 13 women, endometrial cancer was suspected. Complete followup information on diagnostic evaluation and treatment was obtained for 80 percent of the women with abnormal Pap test results. Histological confirmation of neoplasia was reported for 173 women. The diagnoses were cervical dysplasia in 108, cervical cancer in 58 (49 in situ, 9 invasive) and endometrial cancer in 7. The program reached greater proportions of older women, the less affluent, women of Spanish origin and oriental women and a smaller proportion of blacks than were present in the general female population of California.
Objective: Human papillomavirus (HPV) is the major cause of cervical carcinoma and cervical intraepithelial neoplasia worldwide. Certain HPV types have a strong association with and probably a causative role in the
pathogenesis of premalignant cervical lesions. Epidemiologic studies in women infected by the human immunodeficiency
virus (HIV) have shown an increased incidence of squamous intraepithelial lesions (SILs), whichwere predominantly
high-grade. Six to 30 per cent of women diagnosed with atypical squamous cells of undetermined
significance (ASCUS) on a Papanicolaou (Pap) smear harbor SIL in normal screening populations. This study was
undertaken to determine the presence of low- and high-risk HPV types in women infected by HIV and to correlate
the results to those of the Pap smear.
Study design: HPV DNA typing (low- and high-risk) by Digene™ (Digene Corporation, Gathesburg, MD) hybrid capture methodology was performed on cervical swabs from 209 HIV-positive women. The results of HPV typing
were correlated with those of the Pap smear in a retrospective analysis.
Results: One hundred and one women (48%) tested positive for HPV subtypes by DNA typing by the hybrid capture method. Of these, 64 patients (63%) had Pap smears whichwere read as being normal, having benign cellular
changes, or having ASCUS (favor reactive process). Of these, 19 patients tested positive for both high-risk and
low-risk subtypes, 32 patients tested positive only for high-risk subtypes, and 13 patients tested positive only for
Conclusion: HPV subtyping identifies a significant group of HIV-positive women who are at risk for developing cervical intraepithelial neoplasia, although they may not show significant abnormalities on their Pap smears.
HIV-positive women have an increased risk of invasive cervical cancer but cytologic screening is effective in reducing incidence. Little is known about cervical screening coverage or the prevalence of abnormal cytology among HIV-positive women in Ukraine, which has the most severe HIV epidemic in Europe.
Poisson regression models were fitted to data from 1120 women enrolled at three sites of the Ukraine Cohort Study of HIV-infected Childbearing Women to investigate factors associated with receiving cervical screening as part of HIV care. All women had been diagnosed as HIV-positive before or during their most recent pregnancy. Prevalence of cervical abnormalities (high/low grade squamous intraepithelial lesions) among women who had been screened was estimated, and associated factors explored.
Overall, 30% (337/1120) of women had received a cervical screening test as part of HIV care at study enrolment (median 10 months postpartum), a third (115/334) of whom had been tested >12 months previously. In adjusted analyses, women diagnosed as HIV-positive during (vs before) their most recent pregnancy were significantly less likely to have a screening test reported, on adjusting for other potential risk factors (adjusted prevalence ratio (APR) 0.62, 95% CI 0.51–0.75 p<0.01 for 1st/2nd trimester diagnosis and APR 0.42, 95% CI 0.28–0.63 p<0.01 for 3rd trimester/intrapartum diagnosis). Among those with a cervical screening result reported at any time (including follow-up), 21% (68/325) had a finding of cervical abnormality. In adjusted analyses, Herpes simplex virus 2 seropositivity and a recent diagnosis of bacterial vaginosis were associated with an increased risk of abnormal cervical cytology (APR 1.83 95% CI 1.07–3.11 and APR 3.49 95% CI 2.11–5.76 respectively).
In this high risk population, cervical screening coverage as part of HIV care was low and could be improved by an organised cervical screening programme for HIV-positive women. Bacterial vaginosis testing and treatment may reduce vulnerability to cervical abnormalities.
Cancer of the cervix is the most common cancer in women in Swaziland where most women never undergo cervical screening. The extremely high prevalence of HIV/AIDS in Swaziland complicates the management of preinvasive and invasive cervical cancer. The purpose of this study was to assess the current status of cervical cytology in Swaziland, its strengths and limitations.
The study is a retrospective review of 12,188 conventional cervical smears received by the Central Public Health Laboratory in Swaziland from June 2004 to May 2006.
Review of results showed very high rates of cytologic abnormalities with 43.2% of smears screened reported as abnormal. The percentages of abnormalities were as follows: atypical squamous cells of undermined significance (ASC-US), 19.8%; atypical squamous cells, cannot exclude HSILs (ASC-H), 8.8%; low-grade squamous intraepithelial lesions (LSIL), 9.0%; high-grade squamous intraepithelial lesions (HSIL), 4.6%; squamous cell carcinomas, 0.5%; atypical endocervical cells, 0.6%; and atypical endometrial cells, 0.4%. Just over 5% of smears were inadequate. The highest rates of HSILs and invasive squamous carcinoma occurred in women aged 50–59 years.
This study underscores the need to reduce the incidence of cervical cancer and its precursor lesions in Swaziland women. Based on studies of human papillomavirus (HPV) types in other Southern African countries, current HPV vaccines would reduce the incidence and mortality from cervical cancer in the future, but cervical screening would still be required, both for women already infected with the HPV and for HPV subtypes not covered by current vaccines. The most cost-effective combination of screening modalities such as visual inspection, HPV DNA testing, and cytology should be investigated. Cervical cancer reduction needs to be managed within the greater framework of the HIV/AIDS epidemic.
Cervical screening; low resource communities; HPV
Women infected with human immunodeficiency virus (HIV) may be at higher risk of developing cervical cancer than non infected women. In a pilot study, we assessed the relationships among cervical cytology abnormalities associated to Human Papillomavirus (HPV), HIV infection and Highly Active Antiretroviral Therapy (HAART) on the development of Squamous Intraepithelial lesions (SILs). Out of the 70 HIV infected women from Douala -Cameroon (Central Africa) that we included in the study, half (35) were under HAART. After obtaining information related to their lifestyle and sexual behaviour, cervicovaginal samples for Pap smears and venous blood for CD4 count were collected and further divided into two groups based upon the presence or absence of cervical cytology abnormalities i.e. those with normal cervical cytology and those with low and high Squamous Intraepithelial lesions (LSIL, HSIL).
Assessment was done according to current antiretroviral regimens available nationwide and CD4 count. It was revealed that 44.3% of HIV-infected women had normal cytology. The overall prevalence of LSIL and HSIL associated to HPV in the studied groups was 24.3% (17/70) and 31.4% (22/70) respectively. Among the 22 HSIL-positive women, 63.6% (14/22) were not on antiretroviral therapy, while 36.4% (8/22) were under HAART. HIV infected women under HAART with positive HSIL, showed a median CD4+ T cell count of 253.7 +/- 31.7 higher than those without therapy (164.7 +/- 26.1). The incidence of HSIL related to HPV infection within the study group independently of HAART initiation was high.
These results suggest the need for extension and expansion of the current study in order to evaluate the incidence of HPV infection and cervical cancer among HIV-infected and non HIV- infected women in Cameroon.
HIV-infected women living in resource-constrained nations like Zambia are now accessing antiretroviral therapy and thus may live long enough for HPV-induced cervical cancer to manifest and progress. We evaluated the prevalence and predictors of cervical squamous intraepithelial lesions (SIL) among HIV-infected women in Zambia.
We screened 150 consecutive, non-pregnant HIV-infected women accessing HIV/AIDS care services in Lusaka, Zambia. We collected cervical specimens for cytological analysis by liquid-based monolayer cytology (ThinPrep Pap Test®) and HPV typing using the Roche Linear Array® PCR assay.
The median age of study participants was 36 years (range 23-49 years) and their median CD4+ count was 165/μL (range 7-942). The prevalence of SIL on cytology was 76% (114/150), of which 23.3% (35/150) women had low-grade SIL, 32.6% (49/150) had high-grade SIL, and 20% (30/150) had lesions suspicious for squamous cell carcinoma (SCC). High-risk HPV types were present in 85.3% (128/150) women. On univariate analyses, age of the participant, CD4+ cell count, and presence of any high-risk HPV type were significantly associated with the presence of severely abnormal cytological lesions (i.e., high-grade SIL and lesions suspicious for SCC). Multivariable logistic regression modeling suggested the presence of any high-risk HPV type as an independent predictor of severely abnormal cytology (adjusted OR: 12.4, 95% CI 2.62-58.1, p=0.02).
The high prevalence of abnormal squamous cytology in our study is one of the highest reported in any population worldwide. Screening of HIV-infected women in resource-constrained settings like Zambia should be implemented to prevent development of HPV-induced SCC.
HIV; Cervical Cancer; Screening; Cytology; Zambia
Human papillomavirus (HPV) infection is associated with almost all cases of cervical cancer, and cervical cancer is a common malignancy in women living in developing countries. A cross-sectional study was conducted to determine the prevalence of HPV infection, human immunodeficiency virus (HIV) infection, and cervical cytologic abnormalities in women presenting to a sexually transmitted infections clinic in Kampala, Uganda. In June and July, 2002, 135 women underwent complete physical exams including Papanicolaou (Pap) smears. HIV status was evaluated by serology. Cervical and vaginal swabs were obtained by clinicians and tested for HPV genotypes by PCR/reverse blot strip assay. Of the 106 women with cervical swabs adequate for HPV testing, the HPV prevalence was 46.2% (49/106). HIV prevalence was 34.9% (37/106). High risk genotypes 52, 58, and 16 were the genotypes detected most commonly. Eighteen percent (9/49) of women infected with HPV were found to have genotypes 16 and/or 18. Seventy-three percent (27/37) of HIV-positive women versus 16% (10/63) of HIV-negative women had abnormal Pap smears (P <0.0001). Among HIV-positive women, abnormal Pap smears were associated with the presence of high risk HPV genotypes (P <0.001). The majority of women infected with HPV attending this sexually transmitted infections clinic in Uganda were infected with high risk HPV genotypes other than 16 and 18. Future studies should focus on whether current HPV vaccine formulations, that are limited to high risk genotypes 16 and 18, would be effective at decreasing the burden of cervical cancer in this population.
human papillomavirus (HPV); human immunodeficiency virus (HIV); HPV genotypes; cervical cytologic abnormalities; cervical cancer
In the presence of both HIV infection and cervical intraepithelial neoplasia (CIN), the risk of cancer development despite treatment may be greater. We investigated clinical predictors of persistent cytological abnormalities in women who had had a large loop excision of the transformation zone (LLETZ).
Women with high grade squamous intraepithelial lesions or worse (HSIL), less severe abnormalities which persisted and any abnormality in women who are HIV-infected, were referred to the colposcopy clinic. HIV infection was ascertained by self-report. A LLETZ was performed on all patients with HSIL or higher on Papanicolaou (Pap) smear or colposcopy, LSIL or higher in patients who are HIV-infected, where the colposcopy is inadequate, and when there was a discrepancy between colposcopy and cytology by one or more grades. Women with abnormal follow-up smears were compared to those with normal smears. We examined the association between abnormal follow-up smears and demographic and clinical predictors using logistic regression
The median time between LLETZ and first follow-up Pap smear was rather short at 122 days. Persistent cytological abnormalities occurred in 49% of our patients after LLETZ. Predictors of persistence included the presence of disease at both margins and HIV infection. Among the latter, disease at the excision margins and CD4+ cell count were important predictors. In these women, disease at the endocervical margin, both margins, and disease only at the ectocervical margin were associated with increased odds of persistent abnormalities on follow-up cervical smear.
We showed extremely high risk of cytological abnormality at follow-up after treatment more so in patients with incomplete excision and in the presence of immunocompromise. It remains uncertain whether recurrent CIN is a surrogate marker for invasive cervical cancer.
Objective: This report evaluates the acceptance, results, and predictors of human immunodeficiency
virus (HIV) infection in inner city women referred to a colposcopy clinic for abnormal cervical
Methods: HIV testing results of 1,908 inner city women referred for abnormal cervical cytology
were analyzed retrospectively with respect to acceptance, race, ethnicity, Pap smear results, sexually
transmitted diseases (STDs), HIV exposures, and final histologic findings.
Results: HIV testing was accepted by 50.4% of patients. Women who agreed to screening were
significantly more likely to admit exposure to HIV or to be Hispanic, foreign-born, or have a history
of multiple STDs. Of those screened, 3.3% were found to be HIV seropositive. Although higher
grades of referral Pap smears were noted in the women found to be HIV seropositive, final histologic
findings were not different. The only predictors of unknown HIV seropositivity were admitted
HIV exposure and external condyloma.
Conclusions: Fifty percent of inner city women of unknown HIV status referred for abnormal
cervical cytology will accept HIV serotesting and 3.3% are found to be positive. Most HIV-seropositive
women can be detected based on either a history of exposure to HIV or the presence
of external condyloma.
To investigate the role of human papillomavirus (HPV) in the development of cervical neoplasia in women with no previous cervical cytological abnormalities; whether the presence of virus DNA predicts development of squamous intraepithelial lesion; and whether the risk of incident squamous intraepithelial lesions differs with repeated detection of the same HPV type versus repeated detection of different types.
Population based prospective cohort study.
General population in Copenhagen, Denmark.
10 758 women aged 20-29 years followed up for development of cervical cytological abnormalities; 370 incident cases were detected (40 with atypical squamous cells of undetermined significance, 165 with low grade squamous intraepithelial lesions, 165 with high grade squamous intraepithelial lesions).
Main outcome measures
Results of cervical smear tests and cervical swabs at enrolment and at the second examination about two years later.
Compared with women who were negative for human papillomavirus at enrolment, those with positive results had a significantly increased risk at follow up of having atypical cells (odds ratio 3.2, 95% confidence interval 1.3 to 7.9), low grade lesions (7.5, 4.8 to 11.7), or high grade lesions (25.8, 15.3 to 43.6). Similarly, women who were positive for HPV at the second examination had a strongly increased risk of low (34.3, 17.6 to 67.0) and high grade lesions (60.7, 25.5 to 144.0). For high grade lesions the risk was strongly increased if the same virus type was present at both examinations (813.0, 168.2 to 3229.2).
Infection with human papillomavirus precedes the development of low and high grade squamous intraepithelial lesions. For high grade lesions the risk is greatest in women positive for the same type of HPV on repeated testing.
What is already known on this topicPersistence of infection with human papillomavirus (HPV) is thought to have a role in the development of cervical neoplasiaPrevious studies have included only a few cases of high grade squamous intraepithelial lesions, and few have randomly sampled women from the general populationWhat this study addsIn women aged 20-29, HPV infection preceded the development of high grade lesionsPersistent HPV infection with a specific HPV type was an indicator of incident high grade lesions among young women in the general populationThe association between persistence and high grade cervical lesions was more pronounced among women aged over 25
U.S. cervical cancer screening guidelines for HIV-uninfected women 30 years of age and older have recently been revised, increasing the suggested interval between Pap tests from three years to five years among those with normal cervical cytology (the Pap test) who test negative for oncogenic human papillomavirus (HPV). Whether a three-year or five-year screening interval might be used in HIV-infected women who are cytologically normal and oncogenic HPV-negative is unknown.
To determine the risk of cervical pre-cancer or cancer defined cytologically (high-grade squamous intraepithelial lesions or greater [HSIL+]) or histologically (cervical intraepithelial neoplasia 2 or greater [CIN-2+]), as two separate endpoints, in HIV-infected women and HIV-uninfected women who at baseline had a normal Pap test and were negative for oncogenic HPV.
Design, Setting and Participants
Participants included 420 HIV-infected women and 279 HIV-uninfected women with normal cervical cytology at their enrollment in a multi-institutional cohort, between October 1, 2001 and September 30, 2002, with follow-up through April 30, 2011. Clinical sites were in the Bronx, Brooklyn, Chicago, Los Angeles, San Francisco, and Washington, DC. Semi-annual visits included Pap testing and, if indicated, cervical biopsy. Cervicovaginal lavage specimens from enrollment were tested for HPV DNA using PCR. The primary analysis was truncated at five years of follow-up.
Main Outcome Measure
The five-year cumulative incidence of cervical pre-cancer and cancer.
No oncogenic HPV was detected in 369 (88%; 95% CI, 84%-91%) of the HIV-infected women and 255 (91%; 95% CI, 88%-94%) of the HIV-uninfected women with normal cervical cytology at enrollment. Among these oncogenic HPV-negative women two cases of HSIL+ were observed; an HIV-uninfected woman and an HIV-infected woman with a CD4 cell count of 500/μL or greater. Histologic data were obtained from four of the six sites. There were six cases of CIN-2+ in N=145 HIV-uninfected women (cumulative incidence = 5% [95% CI, 1%-8%]) and nine cases in N=219 HIV-infected women (cumulative incidence = 5% [95% CI, 2%-8%]). This included one case of CIN-2+ in N=44 oncogenic HPV-negative HIV-infected women with CD4 cell counts less than 350/μL (cumulative incidence = 2% [95% CI, 0%-7%]), one case in N=47 women with CD4 cell counts of 350 to 499/μL (cumulative incidence = 2% [95% CI, 0%-7%]), and seven cases in N=128 women with CD4 cell counts of 500/μL or greater (cumulative incidence = 6% [95% CI, 2%-10%]). One HIV-infected and one HIV-uninfected woman had CIN-3, but none had cancer.
The five-year cumulative incidence of HSIL+ and CIN-2+ was similar in HIV-infected women and HIV-uninfected women who were cytologically normal and oncogenic HPV-negative at enrollment.
We have retrospectively assessed the incidence and outcome of women diagnosed during a hospital-based cytology screening program with "atypical squamous cells (ASC)" and followed-up with loop electrical excision procedure (LEEP).
We analyzed 173,947 cases of cervical smears' follow-up cytology and histology findings. Previous or archival cytology with LEEP results were retrieved for 390 women with ASC of undetermined significance (ASC-US) and 112 with ASC, cannot exclude high-grade squamous intraepithelial lesion (ASC-H).
On the follow-up cytology, of the 390 women initially diagnosed with ASC-US, 130 (33.3%) had no follow-up records of smears before LEEP; smears of 18 (4.6%) were negative for cytologic abnormalities, 193 (49.5%) were ASC-US, 24 (6.2%) were ASC-H, 111 (28.5%) were low grade squamous intraepithelial lesion (SIL), and 44 (11.4%) were high grade SIL. LEEP findings in these 390 women showed that 183 (46.9%) were negative, 73 (18.7%) were graded as cervical intraepithelial neoplasia (CIN) 1, 25 (6.4%) as CIN 2, 102 (26.2%) as CIN 3, and 7 (1.8%) had carcinoma. LEEP was performed in 112 women initially diagnosed with ASC-H; 36 (32.1%) were negative, 4 (3.6%) were graded as CIN 1, 7 (6.3%) as CIN 2, 60 (53.6%) as CIN 3, and 5 (4.5%) with carcinoma.
Patients with ASC-H smears were at increased risk of SIL or carcnoma compared with patients with ASC-US. Careful follow-up is required in ASC patients.
Cervix uteri; Cytology; Loop electrical excision procedure; Atypical squamous cell
Results of cervical cytology screening showing atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesions (LSIL) indicate risk for high-grade cervical intraepithelial neoplasia (CIN 2 or 3). In a community-based randomized trial we compared the test performance of human papillomavirus (HPV) DNA testing with that of 6-month repeat Papanicolaou (Pap) test in detecting histologically confirmed CIN 2 or 3.
We randomly assigned 212 women aged 16-50 years with ASCUS or LSIL on cervical cytology screening to undergo either immediate HPV DNA testing or a repeat Pap test in 6 months. Cervical swabs for the HPV DNA testing and the Pap smears were obtained by their familiy physicians. We tested the swabs for oncogenic HPV using the Hybrid Capture II assay (Digene Corp., Beltsville, Md.). Community-based pathologists examined the Pap smears. All women were referred for colposcopy by their family physicians. Two gynecological pathologists assessed the histology findings. We calculated test performance in women who completed the trial using CIN 2 or 3 as the reference standard.
A total of 159 women completed the study. Compared with HPV DNA testing, which detected 87.5% (7/8) of the cases of CIN 2 or 3, repeat Pap smear showing high-grade intraepithelial neoplasia (HSIL) detected 11.1% (1/9) of cases (p = 0.004), and repeat Pap smear showing ASCUS, LSIL or HSIL detected 55.6% (5/9) (p = 0.16). Corresponding specificities were 50.6%, 95.2% (p = 0.002) and 55.6% (p = 0.61). Loss to follow-up was 17.1% in the HPV test group and 32.7% in the repeat Pap group (p = 0.009). Given the 7 cases of CIN 2 or 3 detected by HPV testing and the 5 cases detected by the repeat Pap smear, the incremental cost of HPV testing was calculated to be $3003 per additional case of CIN identified.
HPV DNA testing was more costly but was associated with significantly less loss to follow-up. It may detect more cases of CIN 2 or 3 in women with low-grade cytologic abnormalities.
HIV-infected women are at increased risk for developing cervical cancer. Women living in resource-limited countries are especially at risk due to poor access to cervical cancer screening and treatment. We evaluated three cervical cancer screening methods to detect cervical intraepithelial neoplasia grade 2 and above (CIN 2+) in HIV-infected women in South Africa; Pap smear, visual inspection with 5% acetic acid (VIA) and human papillomavirus detection (HPV).
HIV-infected women aged 18–65 were recruited in Johannesburg. A cross-sectional study evaluating three screening methods for the detection of the histologically-defined gold standard CIN-2 + was performed. Women were screened for cervical abnormalities with the Digene HC2 assay (HPV), Pap smear and VIA. VIA was performed by clinic nurses, digital photographs taken and then later reviewed by specialist physicians. The sensitivity, specificity and predictive valves for CIN-2 + were calculated using maximum likelihood estimators.
1,202 HIV-infected women participated, with a median age of 38 years and CD4 counts of 394 cells/mm3. One third of women had a high grade lesion on cytology. VIA and HPV were positive in 45% and 61% of women respectively. Estimated sensitivity/specificity for HPV, Pap smear and VIA for CIN 2+ was 92%/51.4%, 75.8%/83.4% and 65.4/68.5% (nurse reading), respectively. Sensitivities were similar, and specificities appeared significantly lower for the HPV test, cytology and VIA among women with CD4 counts ≤200 cells/mm3 as compared to CD4 counts >350 cells/mm3.
Although HPV was the most sensitive screening method for detecting CIN 2+, it was less specific than conventional cytology and VIA with digital imaging review. Screening programs may need to be individualized in context of the resources and capacity in each area.
We report the prevalence and genotype distribution of human papillomaviruses (HPVs) among Japanese women with abnormal cervical cytology using the PGMY-CHUV assay, one of PGMY-PCR-based lineblot assays that was validated and shown to be suitable for the detection of multiple HPV types in a specimen with minimum bias. Total DNA was extracted from cervical exfoliated cells collected from 326 outpatients with abnormal Pap smears. Overall, 307 specimens (94%) were HPV-positive, 30% of which contained multiple genotypes. The prevalence of HPV DNA was 83% (49/59 samples) in atypical squamous cells of undetermined significance (ASC-US); 91% (20/22 samples) in atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H); 97% (130/134 samples) in low-grade squamous intraepithelial lesion (LSIL); and 99% (85/86 samples) in high-grade squamous intraepithelial lesion (HSIL). Three most frequent HPV types detected in HSIL were HPV16 (36%), HPV52 (24%), and HPV58 (14%). Our results suggest that multiple HPV infections are more prevalent in Japanese women than previously reported, and confirm that HPV52 and 58 are more dominant in their cervical precancerous lesions when compared to those reported in Western countries.
Human papillomavirus; HPV genotyping; cervical cancer; Pap smear; abnormal cytology; HPV vaccine.
The incidence of invasive cervical cancer in HIV-positive women is higher than in the general population. There is evidence that HIV-positive women do not participate sufficiently in cervical cancer screening in Italy, where cervical cancer is more than 10-fold higher in women with AIDS than in the general population. The aim of the present study was to evaluate the history of Pap-smear in HIV-positive women in Italy in recent years. We also examined the sociodemographic, clinical, and organizational factors associated with adherence to cervical cancer screening.
A cross-sectional study was conducted between July 2006 and June 2007 in Emilia-Romagna region (Northern Italy). All HIV-positive women who received a follow-up visit in one of the 10 regional infectivology units were invited to participate. History of Pap-smear, including abnormal smears and subsequent treatment, was investigated through a self-administered anonymous questionnaire. The association between lack of Pap-smear in the year preceding the interview and selected characteristics was assessed by means of odds ratios (OR) and 95% confidence intervals adjusted for study centre and age.
A total of 1,002 HIV-positive women were interviewed. Nine percent reported no history of Pap-smear, and 39% had no Pap-smear in the year prior to the date of questionnaire (last year). The lack of Pap-smear in the last year was significantly associated with age <35 years (OR = 1.4, compared to age ≥45 years), lower education level (OR = 1.3), first HIV-positive test in the last 2 years (OR = 1.4), and CD4 count <200 cells/μl (OR = 1.6). Conversely, when women were advised by a gynecologist rather than other health workers to undergo screening, it significantly increased adherence. Non-significantly higher proportions of lack of Pap-smear in the last year were found in women born in Central-Eastern Europe (OR = 1.8) and Africa (OR = 1.3). No difference in history of Pap-smear emerged by mode of HIV-acquisition or AIDS status.
Three hundred five (34%) women reported a previous abnormal Pap-smear, and of the 178 (58%) referred for treatment, 97% complied.
In recent years the self-reported history of Pap-smear in HIV-positive women, in some public clinics in Italy, is higher than previously reported, but further efforts are required to make sure cervical cancer screening is accessible to all HIV-positive women.
Human papillomavirus (HPV) is responsible for the rising incidence of oropharyngeal squamous cell cancers (OSCC) in the United States (U.S.), and yet, no screening strategies have been evaluated. Secondary prevention by means of HPV detection and cervical cytology has led to a decline in cervical cancer incidence in the U.S. Here, we explored an analogous strategy by evaluating associations between HPV16 infection, cytopathology and histopathology in two populations at elevated risk for OSCC. In the first, a cross-sectional study population (PAP1), cytology specimens were collected by means of brush biopsy from patients presenting with oropharyngeal abnormalities. In the second (PAP2), a nested case-control study, bilateral tonsillar cytology samples were collected at 12-month intervals from HIV-infected individuals. The presence of cytopathological abnormality in HPV16-positive tonsil brush biopsies (cases) was compared to HPV16-negative samples (controls) matched on age and gender. HPV16 was detected in samples by consensus primer PCR and/or type-specific PCR. Univariate logistic regression was used to evaluate associations. In PAP1, HPV16 alone (OR 6.1, 95%CI 1.6–22.7) or in combination with abnormal cytology (OR 20, 95%CI 4.2–95.4) was associated with OSCC. In PAP2, 4.7% (72 of 1524) of tonsillar cytology specimens from HIV-infected individuals without oropharyngeal abnormalities were HPV16-positive. Tonsillar HPV16 infection was not associated with atypical squamous cells of unknown significance (ASCUS), the only cytological abnormality identified. Therefore, HPV16 was associated with OSCC among individuals with accessible oropharyngeal lesions, but not with cytological evidence of dysplasia among high-risk individuals without such lesions. An oropharyngeal Pap-test equivalent may not be feasible, likely due to limitations in sampling the relevant tonsillar crypt epithelium.
oral HPV; tonsillar HPV; head and neck squamous cell cancer; cervical HPV; head and neck cancer screening
Cervical cancer is one of the ten most frequent cancers in Turkey. It is well known that cervical cancer morbidity and mortality could be significantly reduced with an active cervical smear screening (Pap smear) program.
The aims of this study were: 1) to evaluate the knowledge and attitudes of women about cervical smear testing; 2) to establish a cervical smear screening program and to evaluate the cervical cytological abnormalities that were found; 3) to determine the applicability, limitations and effectiveness of this screening in a primary health care unit.
Patients and Methods:
A total of 332 married women were included in our study. We collected data concerning socio-demographic and fertility characteristics, and knowledge about Pap smear testing was determined through printed questionnaires. A gynecological examination and Pap smear screening was performed on every woman in our study group.
Over ninety percent of our study group had never heard of and had not undergone Pap smear screening before. Of the 332 smears evaluated, 328 (98.8%) were accepted as normal, whereas epithelial cell anomalies were seen in 4 (1.2%), infection in 59 (17.7%), and reactive cell differences in 223 (67.2%) of the smears.
The frequency of epithelial cell anomalies in our study group was less than the frequencies reported from Western countries. Knowledge regarding cervical cancer and Pap smear screening was very low. Pap smears can be easily taken and evaluated through a chain built between the primary health care unit and laboratory, and this kind of screening intervention is easily accepted by the population served.
Cervical smear; cervical intraepithelial lesion; cervical cancer screening
Human immunodeficiency virus (HIV)-infected women in India and other developing country settings are living longer on antiretroviral therapy, yet their risk for human papillomavirus (HPV)-induced cervical cancer remains unabated because of lack of cost-effective and accurate secondary prevention methods. Visual inspection after application of dilute acetic acid on the cervix (VIA) has not been adequately studied against the current standard: conventional cervical cytology (Pap smears) among HIV-infected women. We evaluated 303 nonpregnant HIV-infected women in Pune, India, by simultaneous and independent screening with VIA and cervical cytology with disease ascertainment by colposcopy and histopathology. At the cervical intraepithelial neoplasia (CIN2+) disease threshold, the sensitivity, specificity and positive and negative predictive value estimates of VIA were 80, 82.6, 47.6 and 95.4% respectively, compared to 60.5, 59.6, 22.4 and 88.7% for the atypical squamous cells of undetermined significance or severe (ASCUS+) cutoff on cytology, 60.5, 64.6, 24.8 and 89.4% for the low-grade squamous intraepithelial cells or severe (LSIL+) cutoff on cytology and 20.9, 96.0, 50.0 and 86.3% for high-grade squamous intraepithelial lesion or severe (HSIL+) cutoff on cytology. A similar pattern of results was found for women with the presence of carcinogenic HPV-positive CIN2+ disease, as well as for women with CD4+ cell counts <200 and <350 µL−1. Overall, VIA performed better than cytology in this study with biologically rigorous endpoints and without verification bias, suggesting that VIA is a practical and useful alternative or adjunctive screening test for HIV-infected women. Implementing VIA-based screening within HIV/acquired immunodeficiency syndrome care programs may provide an easy and practical means of complementing the highly anticipated low-cost HPV-based rapid screening tests in the near future, thereby contributing to improve program effectiveness of screening.
cervical cancer; visual inspection; cytology; screening; HIV/AIDS; India
Human papillomavirus (HPV) and HIV are each responsible for a considerable burden of disease. Interactions between these infections pose substantial public health challenges, especially where HIV prevalence is high and HPV vaccine coverage low.
Between July 2005 and January 2006, a cross-sectional community-based survey in Mombasa, Kenya, enrolled female sex workers using snowball sampling. After interview and a gynaecological examination, blood and cervical cytology samples were taken. Quantitative real-time PCR detected HPV types and viral load measures. Prevalence of high-risk HPV was compared between HIV-infected and -uninfected women, and in women with abnormal cervical cytology, measured using conventional Pap smears.
Median age of the 820 participants was 28 years (inter-quartile range [IQR] = 24-36 years). One third of women were HIV infected (283/803; 35.2%) and these women were y more likely to have abnormal cervical cytology than HIV-negative women (27%, 73/269, versus 8%, 42/503; P < 0.001). Of HIV-infected women, 73.3% had high-risk HPV (200/273) and 35.5% had HPV 16 and/or 18 (97/273). Corresponding figures for HIV-negative women were 45.5% (229/503) and 15.7% (79/503). After adjusting for age, number of children and condom use, high-risk HPV was 3.6 fold more common in HIV-infected women (95%CI = 2.6-5.1). Prevalence of all 15 of the high-risk HPV types measured was higher among HIV-infected women, between 1.4 and 5.5 fold. Median total HPV viral load was 881 copies/cell in HIV-infected women (IQR = 33-12,110 copies/cell) and 48 copies/cell in HIV-uninfected women (IQR = 6-756 copies/cell; P < 0.001). HPV 16 and/or HPV 18 were identified in 42.7% of LSIL (32/75) and 42.3% of HSIL (11/26) lesions (P = 0.98). High-risk HPV types other than 16 and 18 were common in LSIL (74.7%; 56/75) and HSIL (84.6%; 22/26); even higher among HIV-infected women.
HIV-infected sex workers had almost four-fold higher prevalence of high-risk HPV, raised viral load and more precancerous lesions. HPV 16 and HPV 18, preventable with current vaccines, were associated with cervical disease, though other high-risk types were commoner. HIV-infected sex workers likely contribute disproportionately to HPV transmission dynamics in the general population. Current efforts to prevent HIV and HPV are inadequate. New interventions are required and improved implementation of existing strategies.
Reduction in cervical cancer incidence and mortality is not only dependant on promoting cervical cancer screening but also on providing appropriate follow-up and treatment of abnormal cervical cytology.
The objective of this study was to determine variations in guideline adherence for women requiring abnormal cervical cytology follow-up.
Subjects of the study are women 18 years or older with an abnormal Pap test in 2000 within a large county healthcare system (n = 8,571).
Guideline adherence was determined by the presence or absence of the appropriate follow-up procedure within an acceptable time interval for each degree of cytological abnormality. Patients with no follow-up studies were deemed to be lost to follow-up.
Of study subjects, 18.5% were lost to follow-up care. Of the remaining 6,987 women, 60.3% received optimal care, 9.4% received suboptimal care, and 30.3% received poor care. Follow-up rates were higher for patients with higher degree of cytological abnormality (OR, 1.29, 95% CI, 1.17–1.42), older patients (OR, 1.03, 95% CI, 1.02–1.030) and those receiving the index Pap test at a larger healthcare facility (OR, 1.13; 95% CI, 1.01–1.27). Receiving optimal care was positively correlated with higher degree of cytological abnormality (p < .0001) and larger facility size (p = .002). Regional variations in care demonstrated the largest cluster having the lowest lost to follow-up rate and the most optimal care.
A significant number of women with abnormal cervical cytology are receiving less than optimal care. Further studies are required to determine the specific healthcare delivery practices that need to be targeted to improve guideline adherence for follow-up of abnormal cytology.
cytology; quality of care; practice guidelines; cervical cancer
To estimate the frequency and histologic correlates of glandular abnormalities in cervical cytology among women with the human immunodeficiency virus and to compare findings with those of women without HIV.
In a cohort study of HIV infected and uninfected women followed between 1994 and 2007, Pap tests were obtained every 6 months. Glandular abnormalities, including atypical glandular cells (AGC), adenocarcinoma in situ (AIS), and adenocarcinoma, were identified and correlated with biopsy histology. Multivariate models to summarize data across visits used Generalized Estimating Equations. The association of Pap and histology results was assessed using chi-square tests.
Of 48,362 Pap tests from 3,766 women, glandular abnormalities were found in 341 (0.7%) smears from 244 (6%) women, including 93 (1.0%) of 9,564 Pap tests among HIV-seropositive women with CD4 lymphocyte counts less than 250/cmm, 103 (0.8%) of 13,023 Paps among those with counts 250–500/cmm, 68 (0.6%) of 12,470 Paps among women with counts greater than 500/cmm, and 70 (0.6%) of 11,769 Paps among HIV-seronegative women (P for trend = 0.006). Colposcopy was documented for only 148 (61%) of 244 index Pap tests in women with glandular abnormalities. After index abnormal Paps, endocervical curettings were obtained from 106 (43%) women, cervical biopsies from 76 (38%), and endometrial biopsies from 19 (8%). Squamous lesions predominated among histologic findings and histology results did not differ by HIV serostatus (P = 0.16).
Although immunosuppression increased the risk of glandular Pap abnormalities increased in women with HIV, these remained uncommon. Compliance with management guidelines can improved.