Screening for high-grade cervical intra-epithelial neoplasia and cancer by testing for high-risk HPV, routine cytology or colposcopy

The validity of testing for high-risk types of human papillomavirus (HPV) in cervical cancer prevention programs is undetermined. We compared the performance on primary screening of HPV DNA testing, cytology and colposcopy in detecting cervical intra-epithelial neoplasia (CIN) grade 2 or 3 or cancer. A cohort of 4,761 women, median age 35 years, was screened by routine cytology, routine colposcopy and testing for high-risk HPV by a PCR-based method. Within an 8-month period, women with abnormal findings on cytology or screening colposcopy or in whom high-risk HPV types were detected were referred for colposcopy and biopsy. Women negative on all initial screening tests were followed by a second screening examination. To correct for work-up bias, the true prevalence of CIN 2 or 3 or cancer was estimated by projection from histologically verified subgroups. Cervical biopsies were taken in 364 women (7.6%), of whom 114 (2.4%) showed CIN 2 (n = 34) or CIN 3 (n = 71) or cancer (n = 9). High-risk HPV testing achieved bias-corrected performance measures of 89.4% sensitivity, 93.9% specificity, 35.8% positive predictive value and 99.6% negative predictive value. Bias-corrected rates of true- and false-positives by high-risk HPV testing compared to cytology (colposcopy) were about 4.5 (6.7) and 19.1 (7.4) times higher, respectively. The quality of routine cytology was controlled by computer-assisted review, and the observed number of true-positives more than doubled after adding automated review results. In middle-aged women, testing for high-risk HPV types, particularly when negative, may be used to increase the screening interval in programs for secondary prevention of cervical cancer.     

Prevalence of types 16 and 33 is increased in high-risk human papillomavirus positive women with cervical intraepithelial neoplasia grade 2 or worse

High-risk human papillomavirus (hrHPV) types are causally related to cervical cancer and its high-grade precursor lesions. The risk posed by the different hrHPV types for the development of cervical intraepithelial neoplasia grade 2 or worse (> or =CIN2) needs to be established. Here, we present the hrHPV type-distribution in relation to cytology and histology for women participating in a cervical screening program. From 44,102 women who participated in a population-based cervical screening program in the Netherlands, 2,154 hrHPV GP5+/6+ PCR positive women were recruited to determine the distribution of 14 hrHPV types by reverse line blotting of GP5+/6+ PCR products. For each HPV type, associations with cytology and histologically confirmed > or =CIN2 were measured by odds ratios. HPV types 16 and 33 were more prevalent in women, amongst those containing a single hrHPV type, with moderate dyskaryosis or worse (>BMD) than in women with normal cytology, but only in case of underlying > or =CIN2 (OR 4.10, 95%CI 2.98-5.64 and OR 2.68, 95%CI 1.39-5.15, respectively). Similar results were obtained for women with double infections (OR 3.29, 95% CI 1.61-6.75 and OR 4.37, 95% CI 1.17-16.34). Coexisting types did not influence the prevalence of > or =CIN2 in HPV 16 or 33 positive women. The increased prevalence of type 16 and 33 in hrHPV positive women with > or =CIN2, compared to women with normal cytology, suggests that infection with these types confers an increased risk for development of > or =CIN2. Distinguishing these types may therefore have implications for future cervical screening strategies.     

Initial results of population based cervical cancer screening program using HPV testing in one million Turkish women

To evaluate the Turkey's nationwide HPV DNA screening program on the basis of first 1 million screened women. Women over age 30 were invited for population based screening via HPV DNA and conventional cytology. Samples were collected by family physicians and the evaluations and reports had been performed in the National Central HPV laboratories. The acceptance rate for HPV based cervical cancer screening after first invitation was nearly 36.5%. Since HPV DNA tests have been implemented, cervical cancer screening rates have shown 4–5‐fold increase in primary level. Through the evaluation of all, HPV positivity was seen in 3.5%. The commonest HPV genotypes were 16, followed by 51, 31, 52 and 18. Among the 37.515 HPV positive cases, cytological abnormality rate was 19.1%. Among HPV positive cases, 16.962 cases had HPV 16 or 18 or other oncogenic HPV types with abnormal cytology (>ASC‐US). These patients were referred to colposcopy. The colposcopy referral rate was 1.6%. Among these, final clinico‐pathological data of 3.499 patients were normal in 1.985 patients, CIN1 in 708, CIN2 in 285, CIN3 in 436 and cancer in 85 patients and only pap‐smear program could miss 45.9% of ≥CIN3 cases. The results of 1 million women including the evaluation of 13 HPV genotypes with respect to prevalence, geographic distribution and abnormal cytology results shows that HPV DNA can be used in primary level settings to have a high coverage rated screening program and is very effective compared to conventional pap‐smear.     

Integrating novel primary- and secondary-prevention strategies: the next challenge for cervical cancer control

The advent of prophylactic vaccines against human papillomavirus (HPV) infection, the cause of cervical cancer, and of new molecular methods to screen for this disease have become key developments in cancer control in the last 5 years. Although Pap cytology has had a significant history as a key method for cervical cancer screening, not all countries have benefited from this technology or have been able to implement the necessary public health steps to manage and treat the precancerous lesions that are detected by the Pap test. Testing of cervical exfoliated cells for DNA of oncogenic HPV types has been proven to be more accurate than Pap cytology. The latter test's high specificity makes it an ideal technique to triage women who are found to be HPV positive via a primary screen. HPV testing followed by Pap testing only for HPV-positive women is a promising strategy for screening women in the post-vaccination era.     

Human papillomavirus type-specific 18-month risk of high-grade cervical intraepithelial neoplasia in women with a normal or borderline/mildly dyskaryotic smear.

INTRODUCTION: High-risk human papillomavirus (hrHPV) DNA testing is an increasingly used instrument in cervical cancer prevention along cervical cytology. The inclusion of hrHPV testing in cervical screening requires efficient management as many hrHPV infections are transient. We investigated the potential value of hrHPV genotyping in normal and borderline/mildly dyskaryotic (BMD) smears. MATERIALS AND METHODS: From a screening population of 44,102 women in the Netherlands, we included hrHPV-positive women with a normal or BMD smear. We assessed the type-specific 18-month risk of high-grade cervical intraepithelial neoplasia (CIN). RESULTS: In hrHPV-positive women, 18-month risk of CIN grade 3 or invasive cancer (> or =CIN3) was 6% [95% confidence interval (95% CI), 4-9] after normal cytology and 20% (95% CI, 16-25) after BMD. If positive for HPV16, > or =CIN3 risks were 14% (95% CI, 9-21) and 37% (95% CI, 28-48), respectively. In the subset of hrHPV-positive women without HPV16, HPV18 was associated with an increased risk of high-grade CIN after normal cytology and HPV31 and HPV33 were associated with an increased risk, particularly after BMD. HPV16 and HPV18 were also associated with an increased risk of high-grade CIN in women with an hrHPV-positive normal baseline smear and a repeat normal smear at 6 months. DISCUSSION: HrHPV-positive women without type 16, 18, 31, or 33 had a relatively low risk of high-grade CIN. Among women with baseline normal cytology and among women with a baseline and repeat normal smear, HPV16/18-positive women showed an increased risk of high-grade CIN. This warrants more aggressive management of HPV16/18-positive women compared with other hrHPV-positive women.     

Human papillomavirus types in 115,789 HPV-positive women: A meta-analysis from cervical infection to cancer

Genotyping may improve risk stratification of high-risk (HR) human papillomavirus (HPV)-positive women in cervical screening programs; however, prospective data comparing the natural history and carcinogenic potential of individual HR types remain limited. A meta-analysis of cross-sectional HR HPV-type distribution in 115,789 HPV-positive women was performed, including 33,154 normal cytology, 6,810 atypical squamous cells of undetermined significance (ASCUS), 13,480 low-grade squamous intraepithelial lesions (LSIL) and 6,616 high-grade SIL (HSIL) diagnosed cytologically, 8,106 cervical intraepithelial neoplasia grade 1 (CIN1), 4,068 CIN2 and 10,753 CIN3 diagnosed histologically and 36,374 invasive cervical cancers (ICCs) from 423 PCR-based studies worldwide. No strong differences in HPV-type distribution were apparent between normal cytology, ASCUS, LSIL or CIN1. However, HPV16 positivity increased steeply from normal/ASCUS/LSIL/CIN1 (20-28%), through CIN2/HSIL (40/47%) to CIN3/ICC (58/63%). HPV16, 18 and 45 accounted for a greater or equal proportion of HPV infections in ICC compared to normal cytology (ICC:normal ratios = 3.07, 1.87 and 1.10, respectively) and to CIN3 (ICC:CIN3 ratios = 1.08, 2.11 and 1.47, respectively). Other HR types accounted for important proportions of HPV-positive CIN2 and CIN3, but their contribution dropped in ICC, with ICC:normal ratios ranging from 0.94 for HPV33 down to 0.16 for HPV51. ICC:normal ratios were particularly high for HPV45 in Africa (1.85) and South/Central America (1.79) and for HPV58 in Eastern Asia (1.36). ASCUS and LSIL appear proxies of HPV infection rather than cancer precursors, and even CIN3 is not entirely representative of the types causing ICC. HPV16 in particular, but also HPV18 and 45, warrant special attention in HPV-based screening programs.     

A study of the impact of adding HPV types to cervical cancer screening and triage tests

Use of human papillomavirus (HPV) testing in cervical cancer prevention is increasing rapidly. A DNA test for 13 HPV types that can cause cervical cancer is approved in the United States for co-screening with cytology of women >or=30 years old and for triage of women of all ages with equivocal cytology. However, most infections with HPV are benign. We evaluated trade-offs between specificity and sensitivity for approximately 40 HPV types in predicting cervical intraepithelial neoplasia 3 and cancer in two prospective studies: a population-based screening study that followed 6196 women aged 30-94 years from Costa Rica for 7 years and a triage study that followed 3363 women aged 18-90 years with equivocal cytology in four U.S. centers for 2 years. For both screening and triage, testing for more than about 10 HPV types decreased specificity more than it increased sensitivity. The minimal increases in sensitivity and in negative predictive value achieved by adding HPV types to DNA tests must be weighed against the projected burden to thousands of women falsely labeled as being at high risk of cervical cancer.     

Determination of viral load thresholds in cervical scrapings to rule out CIN 3 in HPV 16, 18, 31 and 33-positive women with normal cytology

An increased high-risk human papillomavirus (hrHPV) viral load in cervical scrapings has been proposed as a determinant for high-grade cervical intraepithelial neoplasia (CIN) and cervical cancer (> or =CIN 2), but data so far for HPV types different from HPV 16 are limited and inconsistent. In addition, a viral load threshold to distinguish hrHPV positive women without > or =CIN 2 still has not been defined. Here, we used baseline cervical scrapings of women with normal cytology participating in a large population-based cervical screening trial (i.e. POBASCAM) who were GP5+/6+-PCR positive for 4 common hrHPV types, i.e. HPV 16, 18, 31 or 33, as a reference to arbitrarily define various viral load thresholds (i.e. 25th, 33rd, 50th, 67th and 75th percentiles of the lowest viral load values) for distinguishing women having single infections with these types without high-grade CIN. Viral load assessment was performed by real time type-specific PCR. The viral load threshold values were subsequently validated on abnormal cervical scrapes of 162 women with underlying, histologically confirmed CIN lesions containing 1 of these 4 hrHPV types. All 59 women with CIN 3 had viral load levels that were higher than those of 33% of the women with normal cytology containing the respective hrHPV type detectable by GP5+/6+-PCR (i.e. higher than the 33rd percentile of viral load). By using this 33rd percentile viral load cut-off, sensitivity for CIN 3 of 100% (95% CI 93.9-100) was obtained. Hence, application of this viral load threshold would increase the specificity of HPV testing for HPV 16, 18, 31 and 33-associated prevalent CIN 3 without the cost of a marked reduction in sensitivity. In practice, on the basis of viral load analysis, a less aggressive management can be foreseen for 33% of the women with normal cytology participating in a population-based screening program who are GP5+/6+-PCR positive for HPV 16, 18, 31 or 33.     

Human papillomavirus DNA testing for cervical cancer screening in low-resource settings

BACKGROUND: In many low-resource settings, there are barriers to cytologic screening for cervical cancer. This study evaluates human papillomavirus (HPV) DNA testing as an alternative screening method. METHODS: Cervical samples from 2944 previously unscreened South African women aged 35-65 years were tested for high-risk types of HPV with the use of the Hybrid Capture I (HCI) assay. Women also had a Pap smear, direct visual inspection of the cervix, and Cervicography(TM). Women positive on any screening test were referred for colposcopy. Samples from women with biopsy-confirmed, low-grade squamous intraepithelial lesions (SILs) (n = 95), high-grade SILs (n = 74), or invasive cervical cancer (n = 12) and a random sample of women with no cervical disease (n = 243) were retested for HPV DNA with the use of the more sensitive Hybrid Capture II (HCII) assay. All P values are two-sided. RESULTS: High-risk HPV DNA was detected in 73.3% and 88.4% of 86 women with high-grade SIL or invasive cancer and in 12.2% of 2680 and 18.1% of 243 women without evidence of cervical disease, with the use of the HCI and HCII assays, respectively. HPV DNA testing with the HCII assay was more sensitive than cytology for detecting high-grade SIL and invasive cancer (McNemar's test, P =.04), and testing with the HCI assay was of equivalent sensitivity (P =.61). Cytology had a statistically significantly better specificity (96.8%) than either the HCI assay (87.8%) or the HCII assay (81.9%) (P<.01). Receiver operating characteristic curves identified test cutoff values that allow HPV DNA testing to identify 57% of women with high-grade SIL or cancer, while classifying less than 5% of women with no cervical disease as HPV DNA positive. CONCLUSIONS: HPV DNA testing has a sensitivity equivalent to, or better than, that of cytology. Since HPV DNA testing programs may be easier to implement than cytologic screening, HPV testing should be considered for primary cervical cancer screening in low-resource settings.     

The absolute risk of cervical abnormalities in high-risk human papillomavirus-positive, cytologically normal women over a 10-year period

In spite of the success of cervical cytology as a cancer-screening tool, it has important limitations, and human papillomavirus (HPV) testing may be valuable in future screening. The majority of women in screened populations, who test HPV positive, will have a concurrent normal smear, and we need more information about the risk for subsequent high-grade cervical lesions in these women. We examined 8,656 younger women (22-32 years old) and 1,578 older women (40-50 years old) who were followed for development of cervical neoplasia (cytology and/or histology) through the Danish Pathology Data Bank. We estimated the proportion of women developing cervical lesions of different types before a given time point as a function of time. Among women with normal cytology and positive high-risk Hybrid Capture 2 (HC2) test, 17.7% and 24.5% of younger and older women, respectively, had a subsequent abnormal Pap smear within 5 years. The risk of CIN3 or cancer within 10 years among younger women with positive HC2 test was 13.6% (10.9-16.2) and 21.2% (2.7-36.1) among older women. An analysis among younger women also being HC2-positive 2 years before baseline showed a subsequent 10-year risk of > or =CIN3 of 18% (14.6-21.5). Among older women where HPV may be added to general screening, the estimated absolute risk of > or =CIN3 in HC2-positive women was more than 20% within 10 years. These results indicate that even a single positive HPV test in cytologically negative women is substantially predictive of high-grade CIN and suggest that HC2 testing can help stratify women into different risk categories.     

Human Papillomavirus (HPV) Prevalence and Type Distribution in Urban Areas of Malaysia

Background: Cervical cancer is the third leading cause of death in Malaysia, and Human Papilloma Virus (HPV) is the principal aetiology that is responsible for its development. This study was aimed to determine the prevalence and distribution of HPV types among different age groups, ethnicity, and areas in Malaysia. Materials and Methods: A total of 764 women aged 20-74 years old within the cities of Johor Bahru, Kuala Lumpur, Ipoh, Penang, and Kota Kinabalu underwent both cervical cytological assessment and HPV DNA analysis. Cervical cytology glass slides were prepared using the liquid base technique (Path TEZT TM). HPV DNA was extracted using TANBead® Nucleic Acid Extraction Kit (Taiwan Advanced Nonotech Inc.), then the types were further identified using a DR.HPV Genotyping IVD kit. Results: The prevalence of HPV infection was 14.0% (107/764) with high-risk type at 10.7% (82/764) and low-risk type at 3.27% (25/764). The most common high-risk HPV types were HPV-52, 66, 33, 39, and 58 whereas low-risk HPV types were HPV-6, 40, and 81. The majority of HPV infections (80.37%) were detected in women with normal cytology results. The most prevalent HPV type among Chinese is 33 (n=6) followed by 16, 44, 58, 66 and 68 (n=5). Among Malays, HPV 16 and 51 were the two most prevalent types (n=2). The sensitivity of the HPV DNA test compared to cytology was 100% with a specificity of 88.37%. Conclusion: This study revealed that the most common high-risk HPV type among women living in urban areas in Malaysia is HPV 52, unfortunately which is not the type of infection the current HPV vaccine is covered for protection among females. These findings may contribute beneficial information to health care providers for the appropriate use of HPV vaccine in the prevention of cervical cancer in Malaysia.     

Detection of Human Papillomavirus in Male and Female Urine by Electrochemical DNA Chip and PCR Sequencing

Background: Cervical cancer is the second most common cancer in Thai women after breast cancer. Currently,the Papanicolaou (Pap) smear is the recommended procedure for cervical cancer screening in Thailand, butonly a relatively small percentage of women follow this screening program. An alternative method to detectHPV genotypes associated with cervical cancer is self-sampling of urine, which is a more widely acceptedmethod. Our study aimed to evaluate the prevalence of HPV in Thai women using urine and cervical swabsand prevalence of HPV in Thai men using urine samples. Materials and Methods: Tumorigenic HPV detectionwas accomplished by electrochemical DNA chip and PCR/direct sequencing. In addition to HPV prevalence,we report the concordance between different methods and sample types. One-hundred and sixteen women and100 men were recruited. Histological examination revealed normal cytology in 52 women, atypical squamouscells of undetermined significance (ASCUS) in 9, low-grade squamous intraepithelial lesions (LSIL) in 24, andhigh-grade squamous intraepithelial lesions (HSIL) in 31. One-hundred men were classified as heterosexuals(n=45) and homosexuals (n=55). Results: The most prevalent HPV genotype in our study was HPV16. The HPVdetection rate was generally lower in urine samples compared with cervical samples. Overall, there was goodagreement for the detection of carcinogenic HPV from female cervical samples between the DNA chip and PCR/sequencing, with 88.8% total agreement and a kappa value of 0.76. In male urine samples, the level of agreementwas higher in heterosexuals compared with homosexuals. Conclusions: Further improvement is required toincrease an overall yield of HPV DNA detection in urine samples before clinical application of a urine-basedHPV screening program. The electrochemical DNA chip test is a promising technique for carcinogenic HPVdetection.     

A comparison of single and combined visual, cytologic, and virologic tests as screening strategies in a region at high risk of cervical cancer.

Increased understanding of human papillomavirus (HPV) infection as the central cause of cervical cancer has permitted the development of improved screening techniques. To evaluate their usefulness, we evaluated the performance of multiple screening methods concurrently in a large population-based cohort of >8500 nonvirginal women without hysterectomies, whom we followed prospectively in a high-risk region of Latin America. Using Youden's index as a measure of the trade-off between sensitivity and specificity, we estimated the performances of a visual screening method (cervicography), conventional cytology, liquid-based cytology (ThinPrep), and DNA testing for 13 oncogenic HPV types. The reference standard of disease was neoplasia > or = cervical intraepithelial neoplasia grade 3 (CIN 3), defined as histologically confirmed CIN 3 detected within 2 years of enrollment (n=90) or invasive cancer detected within 7 years (n=20). We analyzed each technique alone and in paired combinations (n=112 possible strategies), and evaluated the significance of differences between strategies using a paired Z test that equally weighted sensitivity and specificity. As a single test, either liquid-based cytology or HPV DNA testing was significantly more accurate than conventional cytology or cervicography. Paired tests incorporating either liquid-based cytology or HPV DNA testing were not substantially more accurate than either of those two test strategies alone. However, a possibly useful synergy was observed between the conventional smear and cervicography. Consideration of age or behavioral risk profiles did not alter any of these conclusions. Overall, we conclude that highly accurate screening for cervical cancer and CIN 3 is now technically feasible. The remaining vital issue is to extend improved cervical cancer prevention programs to resource-poor regions.     

Detection of human papillomavirus DNA in cytologically normal women and subsequent cervical squamous intraepithelial lesions.

BACKGROUND: Human papillomavirus (HPV) infection has been strongly associated with cervical carcinoma and its cytologic precursors, squamous intraepithelial lesions (SIL). We investigated the risk of SIL prospectively following polymerase chain reaction (PCR)-based DNA testing for a wide range of genital HPV types in a cohort of initially cytologically normal women, to clarify the role of HPV in the etiology of SIL. METHODS: Starting in April 1989, 17,654 women who were receiving routine cytologic screening at Kaiser Permanente (Portland, OR) were followed for the development of incident SIL. During follow-up, 380 incident case patients and 1037 matched control subjects were eligible for this nested case-control study. Cervical lavages collected at enrollment and, later, at the time of case diagnosis (or the corresponding time for selection of control subjects) were tested for HPV DNA using a PCR-based method. The data were analyzed as contingency tables with two-sided P values or, for multivariable analyses, using odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: In comparison with initially HPV-negative women, women who tested positive for HPV DNA at enrollment were 3.8 times (95% CI = 2.6-5.5) more likely to have low-grade SIL subsequently diagnosed for the first time during follow-up and 12.7 times more likely (95% CI = 6.2-25.9) to develop high-grade SIL. At the time of diagnosis, the cross-sectional association of HPV DNA and SIL was extremely strong (OR = 44.4 and 95% CI = 24.2-81.5 for low-grade SIL and OR = 67.1 and 95% CI = 19.3-233.7 for high-grade SIL). HPV16 was the virus type most predictive of SIL, even low-grade SIL. CONCLUSIONS: These findings are consistent with the hypothesis that HPV infection is the primary cause of cervical neoplasia. Furthermore, they support HPV vaccine research to prevent cervical cancer and efforts to develop HPV DNA diagnostic tests.     

Cumulative risk of cervical intraepithelial neoplasia for women with normal cytology but positive for human papillomavirus: Systematic review and meta-analysis

Most women positive for human papillomavirus (HPV) are cytology normal. The optimal screen-management of these women is unclear given their risk of developing precancer. We performed a systematic review and meta-analysis of progression rates to precancer and cancer for HPV-positive, cytology normal women. We searched MEDLINE, EMBASE and Scopus for prospective studies measuring the cumulative incidence of precancer and cervical cancer in HPV-positive, cytology/histology normal women. Record screening was performed independently by two reviewers. We modeled the cumulative incidence over time using a multilevel random-effects meta-regression model. We used the model to predict HPV type-specific risks of precancer and cancer over follow-up. Data from 162 unique records were used in our analysis. The average incidence rate of cervical intraepithelial neoplasia grade 3 or cancer (CIN3+) in high-risk HPV positive but cytology/histology normal women was 1.0 per 100 women-years (95% CI: 1.0-1.1). This corresponds to an average cumulative risk at 1, 3 and 5 years of 2.1% (95% prediction interval 0.0-9.5), 4.3% (95% prediction interval 0.0-11.5) and 6.4% (95% prediction interval 0.0-13.5). HPV type was a strong predictor of the risk of oncogenic progression. There was substantial heterogeneity in the background precancer risk across studies (P-value < .0001). Our HPV type-specific progression risk estimates can help inform risk-based cervical cancer screening guidelines for HPV-positive women. However, precancer and cervical cancer risks are highly variable and may not be generalizable between populations.     

Detection and Type-Distribution of Human Papillomavirus in Vulva and Vaginal Abnormal Cytology Lesions and Cancer Tissues from Thai Women

Vulva and Vaginal cancers are rare among all gynecological cancers worldwide, including Thailand, and typically affect women in later life. Persistent high risk human papillomavirus (HR-HPV) infection is one of several important causes of cancer development. In this study, we focused on HPV investigation and specific type distribution from Thai women with abnormality lesions and cancers of the vulva and Vaginal. A total of ninety paraffin-embedded samples of vulva and Vaginal abnormalities and cancer cells with histologically confirmed were collected from Thai women, who were diagnosed in 2003-2012 at the National Cancer Institute, Thailand. HPV DNA was detected and genotyped using polymerase chain reaction and enzyme immunoassay with GP5/ bio 6 consensus specific primers and digoxigenin-labeled specific oligoprobes, respectively. The human -globin gene was used as an internal control. Overall results represented that HPV frequency was 16/34 (47.1%) and 8/20 (40.0%) samples of vulva with cancer and abnormal cytology lesions, respectively, while, 3/5 (60%) and 16/33 (51.61%) samples of Vaginal cancer and abnormal cytology lesions, respectively, were HPV DNA positive. Single HPV type and multiple HPV type infection could be observed in both type of cancers and abnormal lesion samples in the different histological categorizes. HPV16 was the most frequent type in all cancers and abnormal cytology lesions, whereas HPV 18 was less frequent and could be detected as co-infection with other high risk HPV types. In addition, low risk types such as HPV 6, 11 and 70 could be detected in Vulva cancer and abnormal cytology lesion samples, whereas, all Vaginal cancer samples exhibited only high risk HPV types; HPV 16 and 31. In conclusion, from our results in this study we suggest that women with persistent high risk HPV type infection are at risk of developing vulva and Vaginal cancers and HPV 16 was observed at the highest frequent both of these, similar to the cervical cancer cases. Although the number of samples in this study was limited and might not represent the overall incidence and prevalence in Thai women, but the baseline data are of interest and suggest further study for primary cancer screening and/or developing the efficiency of prophylactic HPV vaccines in Thailand.     

Screening for cervical cancer: is there a place for incorporating tests for the human papillomavirus?

Well organized screening programmes for cervical cancer, based on exfoliative cervical cytology, are known to be effective at reducing the incidence of invasive cervical cancer and mortality from the disease. HPV testing should not replace cervical cytology as the first-line approach in screening for cervical cancer, as HPV testing is not sufficiently reliable and some cancers are not associated with HPV infection. Even though there are many unanswered questions about the validity of HPV tests, it is timely to consider whether HPV testing might improve the management of the substantial number of women whose smears are neither clearly normal nor abnormal, but are described as atypical, suspicious or mildly dyskaryotic. The efficacy and costs of incorporating HPV testing into a cervical cancer screening programme need to be evaluated in controlled trials.     

Comparison of human papillomavirus genotyping and cytology triage,COMPACT Study: Design,methods and baseline results in 14 642 women

Although cytology‐based screening programs have significantly reduced mortality and morbidity from cervical cancer, the global consensus is that primary human papillomavirus (HPV) testing for cervical screening increases detection of high‐grade cervical intraepithelial neoplasia (CIN) and invasive cancer. However, the optimal triage strategy for HPV‐positive women to avoid over‐referral to colposcopy may be setting specific. As Japan requires data that have been generated domestically to modify screening guidelines, we conducted a 3‐year prospective study, COMparison of HPV genotyping And Cytology Triage (COMPACT), to evaluate the potential role of HPV16/18 partial genotyping and cytology for primary HPV screening. In total, 14 642 women aged 20 to 69 years undergoing routine screening at 3 centers in Hokkaido were enrolled. Conventional cytology and HPV testing were carried out. Women with abnormal cytology or HPV16/18 positivity underwent colposcopy. Those with 12 other high‐risk (hr) HPV types underwent repeat cytology after 6 months. Primary study endpoints were detection of high‐grade cervical disease defined as CIN2/CIN3 or greater as determined by consensus pathology. Prevalence of cytological abnormalities was 2.4%. hrHPV, HPV 16, and HPV 18 were detected in 4.6%, 0.9%, and 0.3% of women, respectively. HPV16/18 were detected in all (8/8) invasive cervical cancers and in all (2/2) adenocarcinomas in situ. Both cytological abnormalities and hrHPV positivity declined with increasing age. This is the first Japanese study to investigate the role of partial genotyping and cytology in an HPV‐based screening program. Results should help policy‐makers develop guidelines for future cervical screening programs and management of cervical abnormalities based on HPV genotype.     

Human papillomavirus infection in Ulaanbaatar, Mongolia: a population-based study.

Data on human papillomavirus (HPV) and cervical cancer burden in Central Asia are scarce. To investigate HPV infection in Ulaanbaatar, the capital of Mongolia, we obtained cervical cell specimens from a population of 969 women ages 15 to 59 years. DNA of 44 HPV types was detected using a GP5+/6+ PCR-based assay. Seropositivity for L1 proteins of HPV 16, 18, 31, 33, 45, 52, and 58 was assessed using multiplex HPV serology. Cytologic abnormalities were detected in 127 women (13.1%), among whom 6 cervical intraepithelial neoplasia grade 3 and 2 invasive cervical cancers were diagnosed. Overall HPV DNA prevalence was 35.0%, being highest (48.5%) in women ages <25 years. High-risk types were detected in 24.5% of women. HPV DNA prevalence declined with age but remained >25% in all age groups. HPV seroprevalence was also very high (38.0%) and increased steadily from 33.2% to 48.9% in women ages <25 and 50 to 59 years, respectively. However, the proportion of women positive for both HPV markers of any individual HPV type was low. HPV16 was the most frequently detected type by PCR (6.1%), serology (23.0%), or both (2.1%). Lifetime number of sexual partners and induced abortions were shown to be directly associated with HPV DNA and/or seroprevalence. HPV prevalence in Ulaanbaatar was higher than that detected by similar HPV testing protocols in other populations in Asia or elsewhere and would suggest an important, yet unquantified, cervical cancer burden. Improving cervical cancer prevention, through screening and HPV vaccination, is an important public health issue for Mongolia.     

Anxiety and distress following receipt of results from routine HPV primary testing in cervical screening: The psychological impact of primary screening (PIPS) study

We used a cross-sectional survey to examine short-term anxiety and distress in women receiving different results following routine human papillomavirus (HPV) primary testing at cervical screening. Participants were women aged 24–65 (n = 1,127) who had attended screening at one of five sites piloting HPV primary screening in England, including a control group with normal cytology who were not tested for HPV. Women completed a postal questionnaire ~2 weeks after receiving their screening result. Unadjusted mean anxiety scores ranged from 32.9 (standard deviation [SD] = 12.2) in HPV-negative women to 42.1 (SD = 14.9) in women who were HPV-positive with abnormal cytology. In adjusted analyses, anxiety was significantly higher in women testing HPV-positive with either normal cytology (mean difference [MD] = 3.5, CI: 0.6–6.4) or abnormal cytology (MD = 7.2, CI: 3.7–10.6), than the control group. Distress was slightly higher in women who tested HPV-positive with abnormal cytology (MD = 0.9, CI: 0.02–1.8), than the control group. We also found increased odds of very high anxiety in women who tested HPV-positive with normal or abnormal cytology compared to the control group. This pattern of results was only observed among women receiving their first HPV-positive result, not among women found to have persistent HPV at 12-month follow-up. Testing HPV-positive with normal cytology for the first time, is associated with elevated anxiety despite carrying very low immediate cervical cancer risk. However, receiving the same test result at 12-month early recall does not appear to be associated with higher anxiety, suggesting anxiety may normalise with repeated exposure and/or over time.