HPV mRNA Is More Specific than HPV DNA in Triage of Women with Minor Cervical Lesions

Background

In Norway, repeat cytology and HPV testing comprise delayed triage of women with minor cytological lesions. The objective of this study was to evaluate HPV DNA and HPV mRNA testing in triage of women with an ASC-US/LSIL diagnosis.

Materials and Methods

We used repeat cytology, HPV DNA testing (Cobas 4800) and HPV mRNA testing (PreTect HPV-Proofer) to follow up 311 women aged 25–69 years with ASC-US/LSIL index cytology.

Results

Of 311 women scheduled for secondary screening, 30 women (9.6%) had ASC-H/HSIL cytology at triage and 281 women (90.4%) had ASC-US/LSIL or normal cytology. The HPV DNA test was positive in 92 (32.7%) of 281 instances, and 37 (13.2%) were mRNA positive. Of the 132 women with repeated ASC-US/LSIL, we received biopsies from 97.0% (65/67) of the DNA-positive and 92.9% (26/28) of the mRNA-positive cases. The positive predictive values for CIN2+ were 21.5% (14/65) for DNA positive and 34.6% (9/26) for mRNA positive (ns). The odds ratio for being referred to colposcopy in DNA-positive cases were 2.8 times (95% CI: 1.8–4.6) higher that of mRNA-positive cases. Compared to the mRNA test, the DNA test detected four more cases of CIN2 and one case of CIN3.

Conclusions

The higher positivity rate of the DNA test in triage leads to higher referral rate for colposcopy and biopsy, and subsequent additional follow-up of negative biopsies. By following mRNA-negative women who had ASC-US/LSIL at triage with cytology, the additional cases of CIN2+ gained in DNA screening can be discovered. Our study indicates that in triage of repeated ASC-US/LSIL, HPV mRNA testing is more specific and is more relevant in clinical use than an HPV DNA test.     

Distribution of High-Risk Human Papillomavirus Genotypes among HIV-Negative Women with and without Cervical Intraepithelial Neoplasia in South Africa

Objective

Large studies describing the profile of high-risk Human papillomavirus (hrHPV) genotypes among women in sub-Saharan Africa are lacking. Here we describe the prevalence and distribution of hrHPV genotypes among HIV-negative women in South Africa, with and without cervical intraepithelial neoplasia (CIN).

Methods

We report data on 8,050 HIV-negative women, aged 17–65 years, recruited into three sequential studies undertaken in Cape Town, South Africa. Women had no history of previous cervical cancer screening. Cervical samples were tested for hrHPV DNA using the Hybrid Capture 2 (HC2) assay and all positive samples were genotyped using a PCR-based assay (Line Blot). Women underwent colposcopy and biopsy/endocervical curettage to determine CIN status. The prevalence and distribution of specific hrHPV genotypes were examined by age and CIN status.

Results

Overall, 20.7% (95% CI, 19.9–21.6%) of women were hrHPV-positive by HC2, with women with CIN having the highest rates of positivity. Prevalence decreased with increasing age among women without CIN; but, a bimodal age curve was observed among women with CIN. HPV 16 and 35 were the most common hrHPV genotypes in all age and CIN groups. HPV 45 became more frequent among older women with CIN grade 2 or 3 (CIN2,3). Younger women (17–29 years) had more multiple hrHPV genotypes overall and in each cervical disease group than older women (40–65 years).

Conclusion

HPV 16, 35, and 45 were the leading contributors to CIN 2,3. The current HPV vaccines could significantly reduce HPV-related cervical disease; however, next generation vaccines that include HPV 35 and 45 would further reduce cervical disease in this population.     

Patterns of Human Papillomavirus DNA and Antibody Positivity in Young Males and Females,Suggesting a Site-Specific Natural Course of Infection

Background

To monitor the impact of human papillomavirus types 16 and 18 vaccine on HPV infection dynamics in the Netherlands, we started an ongoing study in sexually transmitted infection (STI) clinics in 2009. Here, we analyze baseline type-specific HPV DNA and HPV-specific antibody positivity rates.

Methods

We enrolled 3569 men and women, 16–24 years of age, from 14 STI clinics, and estimated genital and anal HPV DNA and antibody positivity rates of 7 main carcinogenic HPV types. Generalized estimating equations regression analyses were applied to determine risk factors for, and associations between, type-specific HPV DNA and antibody positivity.

Results

Genital HPV DNA positivity rates were higher in women than in men; anal HPV DNA was especially high in men who have sex with men (MSM). HPV antibody seropositivity rates were also highest in women and MSM. High-risk sexual behavior was predictive of both HPV DNA and antibody positivity. Despite a strong correlation in serological profiles for multiple HPV types, seropositivity was independently associated with homologous HPV DNA detection.

Conclusions

HPV DNA and antibody positivity rates are higher in women and MSM than in heterosexual men, but their association is similar across gender. This suggests a site-specific natural course of infection.     

Effectiveness of VIA, Pap, and HPV DNA testing in a cervical cancer screening program in a peri-urban community in Andhra Pradesh, India

Background

While many studies have compared the efficacy of Pap cytology, visual inspection with acetic acid (VIA) and human papillomavirus (HPV) DNA assays for the detection cervical intraepithelial neoplasia and cancer, few have evaluated the program effectiveness.

Methods and Findings

A population-based sample of 5603 women from Medchal Mandal in Andhra Pradesh, India were invited to participate in a study comparing Pap cytology, VIA, and HPV DNA screening for the detection of CIN3+. Participation in primary screening and all subsequent follow-up visits was rigorously tracked. A 20% random sample of all women screened, in addition to all women with a positive screening test result underwent colposcopy with directed biopsy for final diagnosis. Sensitivity, specificity, positive and negative predictive values were adjusted for verification bias. HPV testing had a higher sensitivity (100%) and specificity (90.6%) compared to Pap cytology (sensitivity  =  78.2%; specificity = 86.0%) and VIA (sensitivity = 31.6%; specificity = 87.5%). Since 58% of the sample refused involvement and another 28% refused colposcopy or biopsy, we estimated that potentially 87.6% of the total underlying cases of CIN3 and cancer may have been missed due to program failures.

Conclusions

We conclude that despite our use of available resources, infrastructure, and guidelines for cervical cancer screening implementation in resource limited areas, community participation and non-compliance remain the major obstacles to successful reduction in cervical cancer mortality in this Indian population. HPV DNA testing was both more sensitive and specific than Pap cytology and VIA. The use of a less invasive and more user-friendly primary screening strategy (such as self-collected swabs for HPV DNA testing) may be required to achieve the coverage necessary for effective reduction in cervical cancer mortality.     

High-Grade Cervical Lesions Among Women Attending A Reference Clinic In Brazil: Associated Factors And Comparison Among Screening Methods

Background

Although screening for cervical cancer is recommended for women in most countries, the incidence of cervical cancer is greater in developing countries. Our goal was to determine the prevalence and factors associated with high-grade lesions/cervical cancer among women attending a reference clinic in Brazil and evaluate the correlation of histology with cytology, colposcopy and the high-risk HPV (HR-HPV) tests.

Methods

A cross-sectional study of women attending a colposcopy clinic was carried out. The patients were interviewed to collect demographic, epidemiological and clinical data. Specimens were collected for cervical cytology, Chlamydia trachomatis and HPV testing using the Hybrid Capture (HC) and PCR tests. Colposcopy was performed for all patients and biopsy for histology when cell abnormalities or cervical intraepithelial neoplasia (CIN) were present.

Results

A total of 291 women participated in the study. The median age was 38 years (DIQ: 30–48 years). The prevalence of histologically confirmed high-grade lesions/cervical cancer was 18.2% (95%, CI: 13.8%–22.6%), with 48 (16.5%) cases of CIN-2/CIN-3 and 5 (1.7%) cases of invasive carcinoma. In the final logistic regression model, for ages between 30 and 49 years old [OR = 4.4 (95%: 1.01–19.04), history of smoking [OR = 2.4 (95%, CI: 1.14–5.18)], practice of anal intercourse [OR = 2.4 (95%, CI: 1.10–5.03)] and having positive HC test for HR-HPV [OR = 11.23 (95%, CI: 4 0.79–26, 36)] remained independently associated with high-grade lesions/cervical cancer. A total of 64.7% of the cases CIN-3\Ca in situ were related to HPV-16. Non-oncogenic HPV were only found in CIN-1 biopsy results. Compared to histology, the sensitivity of cytology was 31.8%, the specificity 95.5%; the sensitivity of colposcopy for high-grade lesions/cervical cancer was 51.0%, specificity was 91.4% and the concordance with HPV testing was high.

Conclusions

The results confirm an association of HR-HPV with precursor lesions for cervical cancer. These data emphasize that cytological screening to detect precursor lesions is still important in some regions and that HR-HPV should be included for screening.     

HPV Testing by cobas HPV Test in a Population from Catalonia

Background

HPV testing in cervical cancer screening has been proposed as an alternative or complementary to cytology in women older than 30 years. However, adequate clinical sensitivity and specificity are crucial for a new test to be implemented. Hybrid Capture 2 (HC2) has proved good clinical performance in selecting women at risk for high-grade intraepithelial lesions with a high sensitivity and specificity. cobas HPV Test has been recently launched and its performance in different clinical settings needs to be determined.

Objectives

The aim of this study was to evaluate the cobas HPV Test for the detection of cervical HPV infection in a population of women in Catalonia (Spain) using HC2 as a reference.

Materials and Methods

Cervical liquid cytology samples from 958 women have been studied. Sensitivity was analyzed in 60 samples from patients with a high-grade intraepithelial lesion (≥CIN2) on histology and specificity was determined in 898 samples from women with no ≥CIN2. All cases had HC2 and cobas HPV Test performed. Statistical analyses of sensitivity, specificity and comparison between HC2 and cobas HPV Test by a non-inferiority test were applied.

Results

Sensitivity of HC2 and cobas HPV Test for detecting ≥CIN2 proved identical (98.3%) while specificity was 85.3% and 86.2% respectively. The non-inferiority test demonstrated that cobas HPV Test surpassed 90% sensitivity and 98% specificity of HC2.

Conclusion

The cobas HPV Test results fulfilled sensitivity and specificity requirements for HPV based cervical cancer screening and for the triage of minor cytological abnormalities, allowing its introduction in clinical settings.     

HPV E6/E7 mRNA testing is more specific than cytology in post-colposcopy follow-up of women with negative cervical biopsy

Background

In Norway, women with negative or low-grade cervical biopsies (normal/CIN1) are followed up after six months in order to decide on further follow-up or recall for screening at three-year intervals. A high specificity and positive predictive value (PPV) of the triage test is important to avoid unnecessary diagnostic and therapeutic procedures whereas a low risk of high-grade disease among triage negative women assures safety.

Materials and Methods

At the University Hospital of North Norway, cytology and the HPV mRNA test PreTect HPV-Proofer, detecting E6/E7 mRNA from HPV types 16, 18, 31, 33 and 45, are used in post-colposcopy follow-up of women with negative or low-grade biopsy. In this study, women with negative biopsy after high grade cytology (ASC-H/HSIL) and/or positive HPV mRNA test in the period 2005–2009 were included (n = 520). Histologically confirmed cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) was used as study endpoint.

Results

Of 520 women with negative or low-grade biopsy, 124 women (23.8%) had CIN2+ in follow-up biopsy. The sensitivity and specificity of the HPV mRNA test were 89.1% (95% CI, 80.1–98.1) and 92.5% (95% CI, 88.2–96.7), respectively. The ratios of sensitivity, specificity and PPV of HPV mRNA testing compared to repeat cytology for finding CIN2+ was 1.05 (95% CI: 0.92–1.21), 1.21 (95% CI: 1.12–1.32), and 1.49 (95% CI: 1.20–1.86), respectively. The PPV of mRNA was 77.3% (95% CI, 59.8–94.8) in women aged 40 or older.

Conclusion

Women with negative cervical biopsy require follow-up before resumption of routine screening. Post-colposcopy HPV mRNA testing was as sensitive but more specific than post-colposcopy cytology. In addition, the HPV mRNA test showed higher PPV. A positive mRNA test post-colposcopy could justify treatment in women above 40 years.     

High-Risk Cervical Human Papillomavirus Infections among Human Immunodeficiency Virus-Positive Women in the Bahamas

Background

High-risk (HR) HPV genotypes other than 16 and 18 have been detected in a significant proportion of immunocompromised females. We aim to evaluate the frequency of HR HPV genotypes in a population of HIV-positive Caribbean women.

Methods

One hundred sixty-seven consecutive, non-pregnant, HIV-positive females ≥18 years were recruited in this study. Each participant received a vaginal examination, PAP smear, and completed a questionnaire. DNA was extracted for HPV testing in 86 patients.

Results

Mean age was 39.1 years for women positive for HR HPV and 43.1 years for women negative for HR HPV (P value  = 0.040). 78% (130/167) of the women had HR HPV infections; the prevalence of abnormal cervical cytology was 38% among women who were HR HPV-positive compared to women who were HR HPV-negative (22%). Fifty-one percent of the 86 women with available genotype carried infections with HPV 16 and/or HPV 18; genotypes of unknown risk were also frequently observed. Women who had a CD4+ count of ≤200 had 7 times increased odds of carrying HR HPV infection in comparison to women with CD4+>200.

Conclusions

HR HPV infections in HIV infected females may consist of more than just HPV 16 and 18, but also HPV 52 and 58. Further studies are needed to determine whether HPV 52 and 58 play a significant role in the development of cervical cytological abnormalities in HIV+ women.     

Triage of women with low-grade cervical lesions--HPV mRNA testing versus repeat cytology

Background

In Norway, women with low-grade squamous intraepithelial lesions (LSIL) are followed up after six months in order to decide whether they should undergo further follow-up or be referred back to the screening interval of three years. A high specificity and positive predictive value (PPV) of the triage test is important to avoid unnecessary diagnostic and therapeutic procedures.

Materials and Methods

At the University Hospital of North Norway, repeat cytology and the HPV mRNA test PreTect HPV-Proofer, detecting E6/E7 mRNA from HPV types 16, 18, 31, 33 and 45, are used in triage of women with ASC-US and LSIL. In this study, women with LSIL cytology in the period 2005–2008 were included (n = 522). Two triage methods were evaluated in two separate groups: repeat cytology only (n = 225) and HPV mRNA testing in addition to repeat cytology (n = 297). Histologically confirmed cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) was used as the study endpoint.

Results

Of 522 women with LSIL, 207 had biopsies and 125 of them had CIN2+. The sensitivity and specificity of repeat cytology (ASC-US or worse) were 85.7% (95% confidence interval (CI): 72.1, 92.2) and 54.4 % (95% CI: 46.9, 61.9), respectively. The sensitivity and specificity of the HPV mRNA test were 94.2% (95% CI: 88.7, 99.7) and 86.0% (95% CI: 81.5, 90.5), respectively. The PPV of repeat cytology was 38.4% (95% CI: 29.9, 46.9) compared to 67.0% (95% CI: 57.7, 76.4) of the HPV mRNA test.

Conclusion

HPV mRNA testing was more sensitive and specific than repeat cytology in triage of women with LSIL cytology. In addition, the HPV mRNA test showed higher PPV. These data indicate that the HPV mRNA test is a better triage test for women with LSIL than repeat cytology.     

Human papillomavirus infection and anxiety: analyses in women with low-grade cervical cytological abnormalities unaware of their infection status

Background

Women testing positive for human papillomavirus (HPV) infection experience increased levels of anxiety that have been attributed to fears of stigmatization and developing cervical cancer. The objective of this study was to investigate the association between HPV infection and anxiety in women who were unaware they had been tested specifically for HPV, to determine if any anxiety experienced by HPV-positive women could be due to causes other than learning of test results.

Methods

This study was nested within a randomised controlled trial of management of women with abnormal cervical cytology conducted in the United Kingdom with recruitment between 1999 and 2002. At baseline, prior to having a sample taken for HPV testing, the results of which were not disclosed, women were assessed for anxiety using the Hospital Anxiety and Depression Scale and asked about fears of developing cervical cancer (“cancer worries”); this assessment was repeated at 12, 18, 24, and 30 months of follow-up. Logistic regression and generalized estimating equations were used for the cross-sectional (baseline) and longitudinal analyses, respectively.

Results

Among the 2842 participants, there was no association between HPV status and anxiety among white women. Among non-white women, however, anxiety was less common among HPV-positive than HPV-negative women (adjusted odds ratio 0.41, 95% confidence interval 0.22 to 0.77). Among non-smokers, cancer worry was more common in HPV-positive than HPV-negative women; the opposite association was observed among ex-smokers.

Conclusions

Associations between HPV status and anxiety may be explained by factors other than learning of test results and may vary by ethnicity and lifestyle factors.     

Risk of Vertical Transmission of Human Papillomavirus throughout Pregnancy: A Prospective Study

Objective

Much controversy still exists about maternal-to-infant transmission of human papillomavirus (HPV) infection, specifically about the magnitude of the risk and the route and timing of such vertical transmission. This prospective cohort study examines the risk of vertical transmission of maternal HPV in each trimester of pregnancy.

Study design

One hundred fifty three healthy pregnant women were followed longitudinally throughout pregnancy and cervical swabs obtained in each trimester and postpartum for HPV detection. Cord blood, neonatal nasopharyngeal aspirates, and placental biopsies were collected at delivery. DNA isolation, polymerase chain reaction, and hybridization were performed using the GG HPV Genotyping Chip Kit (Goodgene Inc., Seoul, Korea). Detection of HPV in neonates was defined as the presence of HPV DNA in either cord blood or neonatal nasopharyngeal aspirate.

Results

HPV DNA was detected in 14%(22/153) of healthy women in the first trimester, 18%(22/124) in the second trimester, and 10%(15/153) in the third trimester; 24%(37/153) were positive for HPV DNA on at least one occasion in pregnancy. At birth, 5.2%(8/153) of neonates were HPV DNA positive. Seven of these eight infants were born to HPV-positive mothers. Placental HPV DNA was positive in 3.3%(5/152) of cases, and all five cases were from mothers with at least one HPV-positive test. Detection of HPV DNA in neonates was associated with detection of HPV in mothers during any of the three trimesters of pregnancy.

Conclusion

HPV DNA was detected at birth in 5.2%(8/153) of neonates born to healthy women, and was associated with the detection of HPV in mothers during any of the three trimesters of pregnancy.     

Primary Screening for Cervical Cancer Based on High-Risk Human Papillomavirus (HPV) Detection and HPV 16 and HPV 18 Genotyping,in Comparison to Cytology

Objectives

The objective of the present study is to assess the performance of a high-risk human papillomavirus (HR-HPV) DNA test with individual HPV-16/HPV-18 genotyping as a method for primary cervical cancer screening compared with liquid-based cytology (LBC) in a population of Greek women taking part in routine cervical cancer screening.

Methods

The study, conducted by the “HEllenic Real life Multicentric cErvical Screening” (HERMES) study group, involved the recruitment of 4,009 women, aged 25–55, who took part in routine cervical screening at nine Gynecology Departments in Greece. At first visit cervical specimens were collected for LBC and HPV testing using the Roche Cobas 4800 system. Women found positive for either cytology or HPV were referred for colposcopy, whereas women negative for both tests will be retested after three years. The study is ongoing and the results of the first screening round are reported herein.

Results

Valid results for cytology and HPV testing were obtained for 3,993 women. The overall prevalence of HR-HPV was 12.7%, of HPV-16 2.7% and of HPV-18 1.4%. Of those referred for colposcopy, cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was detected in 41 women (1.07%). At the threshold of CIN2+, cytology [atypical squamous cells of undetermined significance (ASC-US) or worse] and HPV testing showed a sensitivity of 53.7% and 100% respectively, without change between age groups. Cytology and HPV testing showed specificity of 96.8% and 90.3% respectively, which was increased in older women (≥30) in comparison to younger ones (25–29). Genotyping for HPV16/18 had similar accuracy to cytology for the detection of CIN2+ (sensitivity: 58.5%; specificity 97.5%) as well as for triage to colposcopy (sensitivity: 58.5% vs 53.7% for cytology).

Conclusion

HPV testing has much better sensitivity than cytology to identify high-grade cervical lesions with slightly lower specificity. HPV testing with individual HPV-16/HPV-18 genotyping could represent a more accurate methodology for primary cervical cancer screening in comparison to liquid-based cytology, especially in older women.     

Genital Human Papillomavirus Infection among Women in Bangladesh: Findings from a Population-Based Survey

Background

There has been no population-based study on human papillomavirus (HPV) prevalence or its genotypes in Bangladesh; a country eligible for GAVI funding for HPV vaccine.

Methods

We used baseline survey data of a prospective cohort study that was conducted in one urban and one rural area of Bangladesh. A total of 997 urban and 905 rural married women, aged 13 to 64 years, were enrolled in the baseline during July-December, 2011. Information was collected on socio-demographic characteristics and potential risk factors for HPV infection followed by gynecological examination and collection of endocervical samples using the cervical cytobrush (Digene cervical sampler). HPV DNA testing was done by Polymerase Chain Reaction (PCR) using a consensus primer set.

Results

Prevalence of any HPV infection was 7.7% with no significant difference between urban and rural women. Most common high-risk genotypes were HPV16, HPV66, HPV18, HPV45, HPV31 and HPV53. Urban women working as housemaids or garment workers were at higher risk of any HPV infection (OR = 2.15, 95% CI: 1.13–4.11) compared to housewives. Rural women whose husband lived overseas were almost two times more likely to have any HPV infection (OR = 1.93; 95% CI 1.05–3.55) compared to women whose husbands lived with them.

Conclusion

The prevalence of HPV infection among Bangladeshi women is similar to other regions of Asia. However, type-specific patterns are different. The study findings will inform the formulation of HPV vaccination policies in Bangladesh, monitoring the impact of vaccination programmes, and the identification of target populations for screening.     

Perception of Human Papillomavirus Infection,Cervical Cancer and HPV Vaccination in North Indian Population

Background

Human Papillomavirus (HPV) -associated cervical cancer is the second-most common cancer in women worldwide but it is the most frequent gynaecological cancer and cancer associated death in India women. The objective of this study was to assess knowledge about cervical cancer, HPV, HPV vaccine, HPV vaccine acceptance among school and undergraduates students and their parent’s perception about acceptance of HPV vaccine in Northern part of India (Delhi and NCR regions).

Materials and Methods

A qualitative questionnaire based survey among 2500 urban/rural students aged 12–22 years was conducted.

Results

Overall, a low frequency (15%) of HPV and cervical cancer awareness was observed in students and their parents. However, the awareness was much higher in females belonging to urban setup compared to boys with a perception that HPV causes cervical cancer in women only. Additionally, only (13%) participants who were aware of cervical cancer and HPV) were willing to accept HPV vaccination. Apparently, parents of female students were two times more willing to accept HPV vaccination for their ward than male students (p<0.001; OR 95%CI = 2.09 (1.58–2.76).

Conclusion

Cervical cancer and HPV awareness among school, undergraduate students and also to their parents was found to be very low in this part of India. The level of awareness and education appears to be insignificant determinants in rural compared to urban setup. Better health education will be needed to maximize public awareness for cervical cancer prevention.     

Acceptability and Accuracy of Cervical Cancer Screening Using a Self-Collected Tampon for HPV Messenger-RNA Testing among HIV-Infected Women in South Africa

Background

HIV increases women’s risk for high-risk human papillomavirus (hrHPV) infection and invasive cervical cancer. South Africa has a high HIV prevalence but low cervical cancer screening coverage. Self-collection of cervical specimens and hrHPV testing, including hrHPV messenger-RNA (mRNA) testing, are methods aimed at increasing screening rates. However, data are limited on the acceptability and accuracy of tampon-based self-collection for hrHPV mRNA testing in HIV-infected women.

Methods

We recruited 325 HIV-infected women seeking care at a government HIV clinic in Pretoria, South Africa. A clinician performed a pelvic examination and obtained an endocervical specimen. Study participants performed self-collection using a tampon. Both clinician- and self-collected specimens were tested for hrHPV mRNA. Acceptability of both collection methods was assessed, the prevalence of hrHPV mRNA in our study population was estimated, test positivity of the two collection methods were compared, and test agreement was assessed by calculating the κ-statistic, sensitivity, and specificity.

Results

Over 90% of women reported no difficulties self-collecting specimens and 82% were willing to perform the tampon-collection at home. Based on clinician-collection specimens, the prevalence of hrHPV mRNA in our study population was 36.7% (95% CI: 31.4%– 42.0%). There was no difference in test positivity between clinician-collection, 36.7%, and tampon-collection, 43.5% (p-value = 0.08). Using clinician-collection as the reference test, the sensitivity and specificity for hrHPV mRNA of tampon-collection were 77.4% (95% CI: 69.8–85.0%) and 77.8% (95% CI: 71.9–83.6%), respectively.

Conclusions

Tampon-based self-collection is acceptable to women and has similar hrHPV mRNA positivity rates as clinician-collection, but has reduced sensitivity and specificity compared to clinician-collection. The hrHPV mRNA prevalence in our study population is high, but similar to other high-risk populations, and highlights the need for improved cervical cancer screening. Further research into the optimal use of tampon-based collection as a cervical cancer screening tool is warranted.     

HPV genotypes in high grade cervical lesions and invasive cervical carcinoma as detected by two commercial DNA assays, North Carolina, 2001-2006

Background

HPV typing using formalin fixed paraffin embedded (FFPE) cervical tissue is used to evaluate HPV vaccine impact, but DNA yield and quality in FFPE specimens can negatively affect test results. This study aimed to evaluate 2 commercial assays for HPV detection and typing using FFPE cervical specimens.

Methods

Four large North Carolina pathology laboratories provided FFPE specimens from 299 women ages18 and older diagnosed with cervical disease from 2001 to 2006. For each woman, one diagnostic block was selected and unstained serial sections were prepared for DNA typing. Extracts from samples with residual lesion were used to detect and type HPV using parallel and serial testing algorithms with the Linear Array and LiPA HPV genotyping assays.

Findings

LA and LiPA concordance was 0.61 for detecting any high-risk (HR) and 0.20 for detecting any low-risk (LR) types, with significant differences in marginal proportions for HPV16, 51, 52, and any HR types. Discordant results were most often LiPA-positive, LA-negative. The parallel algorithm yielded the highest prevalence of any HPV type (95.7%). HR type prevalence was similar using parallel (93.1%) and serial (92.1%) approaches. HPV16, 33, and 52 prevalence was slightly lower using the serial algorithm, but the median number of HR types per woman (1) did not differ by algorithm. Using the serial algorithm, HPV DNA was detected in >85% of invasive and >95% of pre-invasive lesions. The most common type was HPV16, followed by 52, 18, 31, 33, and 35; HPV16/18 was detected in 56.5% of specimens. Multiple HPV types were more common in lower grade lesions.

Conclusions

We developed an efficient algorithm for testing and reporting results of two commercial assays for HPV detection and typing in FFPE specimens, and describe HPV type distribution in pre-invasive and invasive cervical lesions in a state-based sample prior to HPV vaccine introduction.     

Distribution patterns of infection with multiple types of human papillomaviruses and their association with risk factors

Background

Infection with multiple types of human papillomavirus (HPV) is one of the main risk factors associated with the development of cervical lesions. In this study, cervical samples collected from 1,810 women with diverse sociocultural backgrounds, who attended to their cervical screening program in different geographical regions of Colombia, were examined for the presence of cervical lesions and HPV by Papanicolau testing and DNA PCR detection, respectively.

Principal Findings

The negative binomial distribution model used in this study showed differences between the observed and expected values within some risk factor categories analyzed. Particularly in the case of single infection and coinfection with more than 4 HPV types, observed frequencies were smaller than expected, while the number of women infected with 2 to 4 viral types were higher than expected. Data analysis according to a negative binomial regression showed an increase in the risk of acquiring more HPV types in women who were of indigenous ethnicity (+37.8%), while this risk decreased in women who had given birth more than 4 times (−31.1%), or were of mestizo (−24.6%) or black (−40.9%) ethnicity.

Conclusions

According to a theoretical probability distribution, the observed number of women having either a single infection or more than 4 viral types was smaller than expected, while for those infected with 2–4 HPV types it was larger than expected. Taking into account that this study showed a higher HPV coinfection rate in the indigenous ethnicity, the role of underlying factors should be assessed in detail in future studies.     

Human Papillomavirus Prevalence in a Population of Women Living in Port-au-Prince and Leogane,Haiti

Background

There have been no published studies of carcinogenic human papillomavirus (HPV)--the necessary cause of cervical cancer--in Haiti, a nation that has one of the greatest burdens of cervical cancer globally.

Objective

Characterize prevalence of carcinogenic HPV and the prevalence of individual carcinogenic HPV genotypes in women with cervical precancer or cancer, cervical intraepithelial neoplasia grade 2 (CIN2) or more severe (CIN2+).

Methods

Women (n=9,769; aged 25-60 years) were screened for carcinogenic HPV by Hybrid Capture 2 (HC2; Qiagen, Gaithersburg, MD). Carcinogenic HPV positives underwent colposcopy and visible lesions were biopsied. A subset of carcinogenic HPV positives was tested for individual HPV genotypes using a GP5+/6+ assay.

Results

The prevalence of carcinogenic HPV was 19.0% (95% confidence interval: 18.4%-19.9%) and decreased with increasing age (p_trend < 0.001). Women with 3 or more sexual partners and who started sex before the age of 18 years had twice the age-adjusted prevalence of carcinogenic HPV of women with one partner and who started sex after the age of 21 (24.3% vs. 12.9%, respectively). HPV16 and HPV35 were the most common HPV genotypes detected in CIN2+ and more common in women with CIN2+ than those without CIN2+. HPV16 and/or HPV18 were detected in 21.0% of CIN2 (n = 42), 46.2% of CIN3 (n = 52), and 80% of cancers (n = 5).

Conclusions

The prevalence of carcinogenic HPV in Haiti was much greater than the prevalence in other Latin American countries. High carcinogenic HPV prevalence and a lack of cervical cancer screening may explain the high burden of cervical cancer in Haiti.     

Costs and Cost Effectiveness of Three Approaches for Cervical Cancer Screening among HIV-Positive Women in Johannesburg,South Africa

Background

South Africa has high rates of HIV and HPV and high incidence and mortality from cervical cancer. However, cervical cancer is largely preventable when early screening and treatment are available. We estimate the costs and cost-effectiveness of conventional cytology (Pap), visual inspection with acetic acid (VIA) and HPV DNA testing for detecting cases of CIN2+ among HIV-infected women currently taking antiretroviral treatment at a public HIV clinic in Johannesburg, South Africa.

Methods

Method effectiveness was derived from a validation study completed at the clinic. Costs were estimated from the provider perspective using micro-costing between June 2013-April 2014. Capital costs were annualized using a discount rate of 3%. Two different service volume scenarios were considered. Threshold analysis was used to explore the potential for reducing the cost of HPV DNA testing.

Results

VIA was least costly in both scenarios. In the higher volume scenario, the average cost per procedure was US$ 3.67 for VIA, US$ 8.17 for Pap and US$ 54.34 for HPV DNA. Colposcopic biopsies cost on average US$ 67.71 per procedure. VIA was least sensitive but most cost-effective at US$ 17.05 per true CIN2+ case detected. The cost per case detected for Pap testing was US$ 130.63 using a conventional definition for positive results and US$ 187.52 using a more conservative definition. HPV DNA testing was US$ 320.09 per case detected. Colposcopic biopsy costs largely drove the total and per case costs. A 71% reduction in HPV DNA screening costs would make it competitive with the conservative Pap definition.

Conclusions

Women need access to services which meet their needs and address the burden of cervical dysplasia and cancer in this region. Although most cost-effective, VIA may require more frequent screening due to low sensitivity, an important consideration for an HIV-positive population with increased risk for disease progression.