Detection of human papillomavirus DNA in cervical smears by the polymerase chain reaction

Abstract. Chetsanga C, Pettersson B, Pettersson U, Gyllensten U. Detection of human papillomavirus DNA in cervical smears by the polymerase chain reaction. Int J Gynecol Cancer 1991; 1 : 209–213.
A PCR-based method has been developed which allows human papillomavirus DNA to be detected in routinely obtained cervical smear specimens. The results showed that 76% of the smears that were collected from women who were carrying HPV-positive lesions by cervical swab analysis were positive by the PCR-based method. The results suggest that it is possible to carry out population-based retrospective studies of archival cervical smears.     

Prevalence of human papillomavirus types 16 and 18 in cervical adenocarcinoma and its precursors in Scottish patients

Our aim was to determine the prevalence of human papillomavirus (HPV) types 16 and 18 in cervical adenocarcinoma (and its precursors) in Scottish patients. Nucleic acid was extracted from paraffin-embedded, formalin-fixed tissues. We examined 119 cases of invasive adenocarcinoma, 20 cases of adenocarcinoma in situ, and 16 cases of normal glandular epithelium. HPV DNA was detected by polymerase chain reaction using type-specific primers for the E6 and E7 genes of HPV-16 and HPV-18 with conformation of HPV genotype by subsequent restriction fragment length polymorphism. HPV DNA was identified in 87 (62.6%) cases, with HPV-16 being detectable in 65 (47%) cases and HPV-18 in 41 (29%) cases. All the cases of normal tissue tested negative for HPV-16 and/or HPV-18. No significant relation between infecting HPV type (16 or 18) and subtypes of disease (within the invasive category and between the preinvasive and the invasive categories) was noted. Our findings support that HPV-16, along with HPV-18, are likely to play a significant role in the pathogenesis of cervical adenocarcinomas and that cervical cancer screening strategies that incorporate oncogenic HPV testing, and prophylactic vaccines that target these types, will be beneficial for the reduction of adenocarcinoma and associated glandular precursors.     

Telomere length in leukocytes and cervical smears of women with high-risk human papillomavirus (HR HPV) infection

ObjectivePersistent high-risk HPV (HR HPV) infection leads to the development of squamous intraepithelial lesions, which in turn may progress to cervical cancer. Telomere elongation or shortening may indicate a carcinogenesis process. In the present study, we analyzed telomere length from blood and cervical smears of women without and with high-risk HPV infection.Materials and methodsTelomere length was quantified by real-time PCR in blood and cervical smears from 48 women with high-risk HPV infection and HGSIL or LGSIL, 29 women HR-HPV positive without SIL, and 11 HPV-negative women.ResultsNo correlation was found between age and telomere length in blood and cervical smears. Women with high-risk HPV infection had shorter telomeres in cervical smears, but not in blood compared to the control group.ConclusionThese findings suggest that telomere shortening occurs in cervical cells of women with HR HPV infection both with LGSIL and HGSIL and may indicate the onset of carcinogenesis. In turn, there is no correlation between leukocyte telomere length and cervical cancer risk in women with HR HPV infection.     

Baseline human papillomavirus status of women with abnormal smears in cervical screening: a 5-year follow-up study in The Netherlands

Objective  To determine in a screening population the human papillomavirus (HPV) status in those with cytological abnormalities and to evaluate the presence of high-risk (HR) HPV with a minimum of 5-year follow up.
Design  Retrospective examination of HPV status on prospectively collected and cytologically screened cervical smears.
Setting  Canisius-Wilhelmina Hospital in Nijmegen, the Netherlands.
Population  Three hundred and fifty-seven women aged 30–60 years, from the population screened.
Methods  Three hundred and fifty-seven women with borderline or higher cytological abnormalities were retrospectively examined for HPV with DNA microarray typing. Follow up was through the nationwide Dutch Pathology database (PALGA).
Main outcome measures  For the cytological abnormalities, the CISOE-A classification was used. HPV was scored as negative or positive. In case of positive HPV polymerase chain reaction, the HPV genotype was determined. The occurrence of cervical intraepithelial neoplasia lesions of grade 3 or higher was considered as endpoint for follow up.
Results  The majority of the women with borderline cytology in this study were HPV negative (87%). Among the HPV-positive women in borderline cytology group, 74% had HR-HPV or probable high-risk types. The overall percentage of HR-HPV types increased with progressive cytological abnormalities. The cytological classifications of borderline dyskaryosis and moderate dyskaryosis contain all types of HPVs, e.g. low risk, HR and unknown risk. The samples with severe dyskaryosis or higher contain only HR types. The negative predictive value for HR-HPV typing in the group with borderline cytological abnormalities is more than 99%.
Conclusions  In cervical screening with an interval of 5 years, HPV can be reliably used as triage point in cases of borderline cytological abnormalities.     

Prevalence and risk factors for human papillomavirus DNA in cervical cytology

Objectives

This study aimed to detect the presence and prevalence of HPV-DNA in the cervical swab samples obtained from patients with cervical cancer, premalignant cervical lesions and benign cervical smear results, and to identify the potential risk factors influencing this prevalence.

Study design

Smear preparations were examined and classified according to the Bethesda system. HPV-DNA detection and genotyping was carried out using polymerase chain reaction combined with reverse hybridization line-probe assays. Age, smoking habit, age at first sexual intercourse, number of sexual partners, number of term births, contraceptive method, progesterone therapy, history of sexually transmitted diseases, history or existence of warts, existence of cervical infection and the history of circumcision of male sexual partners were recorded.

Results

Six hundred and forty-two women (96 women with abnormal cervical cytology and 546 women with normal cytology) provided cervical samples. Multiplex PCR testing revealed that prevalence of HPV-DNA was 38.9% in our study population. HPV-DNA was detected in 78.3% of the women with cervical cancer and 76.9% of the women with HGSIL. Abnormal cervical cytology was observed in 30% of HPV-DNA positive cases and in 5.4% of HPV-DNA negative cases. Our findings also indicate that smoking habit, number of sexual partners, history of sexually transmitted diseases, and abnormal cervical cytology were associated with HPV infection. With respect to parity, there was a decreased risk of HPV infection with the increase in the number of births.

Conclusions

Estimates of the prevalence of HPV infection vary greatly around the world, so the factors that contribute to the rare occurrence of cervical cancer after HPV infection might also differ from country to country. Information gathered from this study could be used to prioritize limited screening and treatment services given to woman who have specific characteristics that may put them at an increased risk of HPV disease.     

Distribution of various types of low-risk human papillomavirus according to cervical cytology and histology in northern Chinese women

Objective

To describe the distribution of specific types of low-risk (LR) human papillomavirus (HPV) among a general population of northern Chinese women.

Methods

Between 2007 and 2012, 118 096 women were tested with the HPV Geno-Array Test Kit (HybriBio) at China Medical University’s Shengjing Affiliated Hospital, Shenyang, China. Among these women, 80 418 underwent cervical cytology and colposcopic examination, and 30 961 of these had a cervical biopsy. The prevalence of HPV infection among the women was analyzed according to age, and cytologic and histologic findings.

Results

CP8304 was the most common type of LR-HPV overall, and was most prevalent in the youngest age group. The overall prevalence of LR-HPV (averaged across all types) was 1.7% in women with normal cytology, 8.8% in those with atypical squamous cells of undetermined significance (ASCUS), 8.0% in those with low-grade squamous intraepithelial lesions (LSIL), and 5.8% in those with high-grade squamous intraepithelial lesions (HSIL). LR-HPV alone, without any high-risk (HR)-HPV, was most common among women with ASCUS and cervical intraepithelial neoplasia (CIN) not otherwise specified (CINNOS) together. Co-infections of LR-HPV and HR-HPV were most common among women with LSIL and CIN1.

Conclusion

These data will facilitate modeling of the cost-effectiveness of a prophylactic LR-HPV vaccination in China.     

Characterization of human papillomavirus genotypes and HPV-16 physical status in cervical neoplasias of women from northern Portugal

Objective

To determine human papillomavirus (HPV) genotypes and the physical status of HPV-16 DNA among women from northern Portugal with cervical lesions.

Methods

The present retrospective study included samples of cervical exfoliated cells from 88 women (median age 42.0 ± 13.1 years) who attended the Gynecology Service at the Portuguese Institute of Oncology in Porto during 2010. After DNA extraction, HPV genotyping was performed by polymerase chain reaction (PCR) followed by restriction fragment length polymorphism analysis using the MY09/MY11 primers. The physical status of HPV-16 was determined by real-time PCR.

Results

Overall, 69.3% of the samples tested positive. The prevalence of HPV infection was 38.5% in normal samples, 57.7% in cervicitis samples, and 87.2% in all cervical lesions including invasive cancers. Sixteen genotypes were detected, the most prevalent ones being HPV-16 (42.9%), HPV-31 (12.2%), and HPV-58 (10.2%); HPV-18 was rare. The overall prevalence of HPV-16 integration was 31.6%. The physical status of HPV-16 did not differ significantly by histology.

Conclusion

The most frequent genotypes were HPV-16, -31, and -58. Integration of HPV-16 DNA seemed to be an early event in cervical carcinogenesis. Further studies are required to clarify the value of viral integration as a prognostic marker.     

Detection and quantitation of human papillomavirus type 16, 18 and 52 DNA in the peripheral blood of cervical cancer patients

OBJECTIVE: To prospectively evaluate the feasibility of detecting human papillomavirus (HPV) type 16, 18 and 52 DNA in the peripheral blood of patients with cervical cancer using real-time polymerase chain reaction (PCR) and to determine its prognostic importance. METHODS: Blood and cervical swab specimens from 135 consecutive patients with 60 invasive cervical cancers, 10 microinvasions, 20 cervical intraepithelial neoplasias (CIN) III, 10 CIN II, 10 CIN I and 25 controls were collected and examined for HPV type 16, 18 and 52 DNA using real-time PCR to investigate the prevalence and viral load of HPV DNA at the time of diagnosis and during follow-up in patients with positive blood samples. RESULTS: Of the 60 patients with invasive cervical cancer, 27% had positive test results for HPV DNA in blood samples in contrast to 0% of patients with microinvasions, CIN III, CIN II, CIN I and normal controls. The DNA detection rates of viral subtypes in blood samples of cervical cancer patients were 5% for HPV-16, 16.7% for HPV-18, 8.3% for HPV-52, 1.7% for both HPV-16 and HPV-18 and 1.7% for both HPV-18 and HPV-52, while the detection rates in cervical swab specimens were 36.2% for HPV-16, 15.5% for HPV-18 and 17.2% for HPV-52. During follow-up, 8 of 10 cervical cancer patients with viral DNA detected in blood within 3 months after treatment had recurrence, and a high percentage (87.5%, 7/8) of this recurrence involved distant metastases. CONCLUSIONS: In this study, real-time PCR detected HPV-16, -18 or -52 DNA in the peripheral blood of more than one-fourth of invasive cervical cancer patients. The association between risk of cancer recurrence and the amount of viral DNA detected in blood among cervical cancer patients after treatment is intriguing and deserves further investigation.     

Prevalence of HPV infection by cervical cytologic status in Brazil

Objectives

To assess the prevalence of human papillomavirus (HPV) infection according to cervical cytologic status in northeastern Brazil; identify other risk factors for low- and high-grade squamous intraepithelial lesions (LSILs and HSILs); and identify the most prevalent HPV genotypes associated with the lesions.

Method

Two cervical smears were collected from 250 women referred for cancer screening, one for cytologic examination and the other to test for the presence of HPV by PCR with genotyping by dot blot hybridization.

Result

There were 110 healthy cervices, 82 LSILs, and 58 HSILs. The overall HPV prevalence was 48%, with higher rates for HSILs, and HPV-16 was the most prevalent type. Age, multiple sexual partners, type of HPV present, smoking, and early onset of sexual activity were risk factors for cervical lesions.

Conclusion

Age, multiple sexual partners, and infection with HPV-16 increased the risk of having LSILs or HSILs. Early onset of sexual activity and smoking only increased the risk of having HSILs.     

HIV/AIDS与人乳头瘤病毒感染及宫颈病变的相关性研究

目的:探讨艾滋病病毒感染者/艾滋病患者(HIV/AIDS)生殖道高危型人乳头瘤病毒(HR-HPV)感染及宫颈病变的特点,为HIV/AIDS患者宫颈癌的防治研究提供线索和依据.方法:选取2009年4月至2012年7月就诊于我院的166例HIV/AIDS患者[HIV(+)组]与476例非HIV感染患者[HIV(-)组],比较两组患者的HR-HPV感染率及液基细胞学检测(TCT)检测结果.结果:HIV(+)组的HR-HPV感染率(38.55％,64/166)显著高于HIV(-)组(10.50％,50/476)(P＜0.001).HIV(+)组中20例行宫颈活检,其中13例(65.00％)发生CIN Ⅰ以上病变;HIV(-)组中21例行宫颈活检,19例(90.48％)发生CIN Ⅰ以上病变.HIV(+)组中HR-HPV(+)与HR-HPV(-)者的CD4＜200cell/μl的比率分别为29.29％和17.48％,差异显著(P=0.03).结论:HIV/AIDS患者感染HR-HPV的风险显著高于非HIV感染者,对HIV-HPV联合感染者应进行连续追踪观察.HIV/AIDS患者感染HR-HPV可能与免疫系统的破坏程度有关.     

高危型人乳头瘤病毒检测在宫颈癌筛查中的应用价值

目的探讨将HR-HPV检测作为宫颈癌筛查手段的意义和价值。方法2004-12-2005-04对301医院妇产科门诊就诊的1231例患者,进行HPVDNA的杂交捕获法二代(HPV-HCⅡ)和液基细胞学(Thinprepcytol-ogytest,TCT)的检测,作为宫颈癌及其癌前病变的初筛。131例因细胞学异常,或细胞学正常而HPV检测阳性,或细胞学正常HPV阴性、而临床高度怀疑病变的患者行阴道镜下多点活检,结合病理结果进行分析。结果(1)1231例样本中,经TCT检测正常者1077例(87·43%),ASCUS32例(2·60%),ASCUS-H34例(2·76),LSIL73例(5·93%),HSIL15例(1·22%)。131例阴道镜下多点组织活检,病理证实炎症68例(51·91%),CINⅠ20例(15·27%),CINⅡ18例(13·74%),CINⅢ16例(12·21%),浸润癌4例(4·35%),湿疣5例(3·82%)。(2)HPV总感染率34%,HPV阳性者418例,年龄平均(36·93±10·8)岁,HPV阴性者813例,年龄平均(39·68±11·8)岁,HPV阳性组的年龄明显小于HPV阴性组,P<0·01。各病理组HPV感染率分别为:炎症58·82%,CINⅠ80%,CINⅡ72·22%,CINⅢ100%,浸润癌100%,湿疣60%。(3)阴道镜下多点活检结果:TCT和HPV均(-)者,无高度病变的发生;TCT(-)和HPV( )者中,≥CINⅡ的检出率11·1%(1/9),TCT异常和HPV阳性同时存在的病例中,≥CINⅡ的检出率最高40·5%(32/79);仅TCT异常而HPV(-)者13·2%(5/38),且5例均为CINⅡ,无原位癌和浸润癌的发生。结论持续的HR-HPV感染与宫颈病变的演进有关;HR-HPV检测是有价值的辅助诊断技术,与细胞学联合检测,为最佳宫颈癌筛查方案。     

A PCR study on the coexistence of herpes simplex virus, cytomegalovirus and human papillomavirus DNAs in cervical neoplasia

There is strong epidemiological and biological evidence that the development of squamous cell carcinoma of the cervix is a multistep process in which human papillomaviruses (HPVs) play a crucial but not total role and where the synergistic effect of herpes simplex virus (HSV) and human cytomegalovirus (HCMV) has been suggested. The presence of HPV, HSV and HCMV deoxyribonucleic acids (DNAs) was assessed by a polymerase chain reaction (PCR) in cervical biopsies obtained from 41 women with cervical neoplasia (21 high-grade cervical intra-epithelial neoplasia (CIN) and 20 squamous cell cancers) and 33 controls. Human papillomavirus 16 DNA was significantly more common in high-grade CIN (57%) and cancer (50%) than in normal cervix (9%). Herpes simplex virus and HCMV DNAs were present in 12% and 21% of normal cervices, 19% and 24% of high-grade CIN, and 25% and 25% of cancers, respectively. After adjustment for patients' age, coinfection associating high-risk HPVs (HPV 16 and/or HPV 18) and herpes viruses (HCMV and/or HSV) were observed in cervical neoplasia (odds ratio (OR) = 19.11; 95% confidence interval (CI): 2.14–170.36). Conversely, the OR for infection by HPV 16 and/or HPV 18 alone did not reach statistical significance (OR = 7.22; 95% CI: 0.85–61.16). Moreover infection by HCMV and/or HSV alone (OR = 0.89; 95% CI: 0.33–2.24) was not associated with cervical neoplasia. Our results support the role of HSV and HCMV as cofactors of HPV 16 and HPV 18 in cervical neoplasia.     

Occurrence of human papillomavirus DNA types 16 and 18 (HPV-16/18) in cervical smears as compared to cytological findings

Cervical smears from 2336 women were examined for the presence of HPV-16/18 by dot-blot hybridization using 32P-labeled HPV-16/18 DNA under high stringency conditions. The hybridization data were compared with cytological findings classified according to Papanicolaou. The ages of the patients ranged from under 20 to over 70 years. Ninety-eight (4.4%) of the 2237 cytologically normal cervical samples (Pap I and II) were HPV-16/18 positive. Thirteen out of 32 (40.6%) samples showing signs of mild and moderate dysplasia (Pap IIID) were found to be HPV-16/18 positive. In 5 out of 7 (71.4%) samples from women with severe dysplasia or carcinoma in situ (Pap IV) and in 9 out of 25 (32.1%) samples from patients with invasive cervical carcinoma (Pap V) HPV-16/18 DNA was detected. Thirty-two smears were from women with severe unspecific cervical inflammation (Pap III). Two (6.2%) out of them were HPV-16/18 positive. Normal smears showed an apparent age-dependent pattern of HPV-16/18 positivity with a peak prevalence of 10.6% among women younger than 20 years old. The majority of premalignant lesions was detected among women younger than 40 years old; whereas all invasive lesions were from women older than 39 years. Compared to the HPV-16/18 prevalence rate in normal smears, abnormal smears harbored HPV-16/18 DNA approximately 9 times more frequently. This finding supports the hypothesis that HPV-16/18 may be involved in the development of cervical cancer.     

Infection by human papillomavirus types 6, 11, 16, 18, 31, 33 and 35 of the cervix in Japanese women

Exfoliated cervical cells from 321 Japanese women were examined for human papillomavirus (HPV) DNA types 6, 11, 16, 18, 31, 33 and 35 using polymerase chain reaction (PCR) and dot-blot hybridization methods. HPV DNA was present in 9.3% of patients with normal cervixes, 72.7% of patients with cervical intraepithelial neoplasia (CIN) and 77.8% of patients with invasive carcinoma. Younger patients (29 years) with normal cervixes had a 18.5% incidence of HPV DNA, whilst similar older patients (50 years) had a 1.9% incidence, a significant difference (χ²= 6.478, P < 0.01). In the CIN I and II groups, an incidence of 11.1% of types 16 and 18 was found, while in the CIN III or invasive carcinoma group the incidence was 58.1%, again a significant difference (χ² = 12.075, P < 0.01). Furthermore, persistence or progression of CIN showed a significant correlation with infections by types 16 and 33 (χ²= 4.904, P < 0.01). However, no significantly different incidence of HPV infection was found between the CIN and the invasive carcinoma groups. It is suggested that (a) younger patients with normal cervixes have a higher incidence of HPV infection than do older patients; (b) HPV types 16, 18 and 33 are important etiologic agents of CIN III and invasive carcinoma, as well as in the persistence and progression of CIN; (c) progression of CIN to invasive carcinoma may depend on factors other than HPV infection in the cervix.     

Human papillomavirus type 18 and other risk factors for cervical cancer in Jakarta, Indonesia

Infection with human papillomavirus (HPV) has now been established as a necessary cause of cervical cancer. Indonesia is a country with a high cervical cancer incidence and with the world's highest prevalence of HPV 18 in cervical cancer. No information exists about the prevalence of HPV 18 or other HPV types in the Indonesian population. We conducted a hospital-based case-control study in Jakarta, Indonesia. A total of 74 cervical carcinoma cases and 209 control women, recruited from the gynecological outpatient clinic of the same hospital, were included. All women were HPV typed by the line probe assay, and interviews were obtained regarding possible risk factors for cervical cancer. HPV was detected in 95.9% of the cases and in 25.4% of the controls. In the control group, 13.4% was infected with a high-risk HPV type. HPV 16 was detected in 35% of the case group and in 1.9% of the control group and HPV 18 was identified in 28% of the case group and in 2.4% of the control group, suggesting that the oncogenic potentials of HPV 16 and HPV 18 in Indonesia are similar. In addition to HPV infection, young age at first intercourse, having a history of more than one sexual partner, and high parity were significant risk factors for cervical cancer. Within the control group, we did not identify determinants of HPV infection. We hypothesize that the high prevalence of HPV 18 in cervical cancer in Indonesia is caused by the high prevalence of HPV 18 in the Indonesian population.     

Acceptability of self-collected human papillomavirus specimens in cervical cancer screening: A review

Cervical cancer morbidity and mortality is an important public health problem around the world. Some of the barriers to cervical cancer screening include the embarrassment, discomfort, lack of privacy and time and cost associated with clinician-collected, clinic-based screening with cytology or human papillomavirus tests. Self-collection of a human papillomavirus (HPV) test has been found to be generally more acceptable, less embarrassing, more comfortable, more private and easy to do and preferred to pelvic examination for cervical cytology by many women worldwide. The most commonly reported limitation to self-collection is a woman’s lack of confidence in her ability to perform it correctly. Self-collected human papillomavirus tests have been shown to be as or more sensitive than cytology or clinician-collected HPV tests. With confidence-building education about self-collection, it is likely a viable method to extend the reach of screening in high and low-resource areas around the world.     

A study of women's knowledge regarding human papillomavirus infection, cervical cancer and human papillomavirus vaccines

AIMS: Human papillomavirus (HPV) infection is a common sexually transmitted viral infection and is associated with the development of cervical cancer. HPV vaccines are now undergoing phase 3 clinical trials in Australia. It is likely that an HPV vaccine will become licensed for use in the near future. METHODS: Ninety women aged 18-30 years from three different groups (those attending a dysplasia clinic, a local university health service and participants currently involved in a phase 3 HPV vaccine trial) completed a questionnaire assessing their knowledge base regarding HPV infection, cervical cancer, Pap tests and HPV vaccines. RESULTS: Respondents demonstrated good understanding of the Pap test and interpretation of an abnormal result. Most respondents (89%) had heard of HPV and attributed a number of different clinical symptoms to infection. For women who had not heard of an HPV vaccine, 79% of respondents stated that the most common resource they would use to obtain further information is their general practitioner. DISCUSSION: Many women do not understand the risk factors for HPV infection, the clinical problems it may cause and the potential long-term complications of infection. Few women have heard of a HPV vaccine, but most women surveyed would approach their general practitioner for more information if one became available. CONCLUSION: This study highlights the need for further education regarding HPV infection and the potential long-term complications such as cervical cancer. It also demonstrates that education of general practitioners regarding an HPV vaccine is essential, as this is the most likely resource women will use to obtain further information in the future.     

Age-specific detection of high risk HPV DNA in cytologically normal, computer-imaged ThinPrep Pap samples

OBJECTIVE: Recent cervical cancer screening guidelines for women over age 30 seek to improve the sensitivity of cytology by incorporating high-risk (HR) human papillomavirus (HPV) DNA testing into the screening algorithm, a recommendation based largely on data that utilized the conventional Pap smear and were not stratified by patient age. Data on the rate of HR HPV among women over age 30 undergoing liquid-based Pap test screening are limited. The objective of this study was to determine the rate of HR HPV DNA positivity in women ages 30 and over with a cytologically negative liquid-based Pap test result. METHODS: Consecutive residual ThinPrep Pap samples from women with a cytologically negative result following computer-assisted screening were tested for HR HPV using the Hybrid Capture 2 (HC2) method. All HC2-positive samples were additionally tested with the Linear Array (LA) HPV Genotyping Test. RESULTS: 1000 cytologically negative specimens from women aged 30 to 45 years (38.9+/-4.7 years) were evaluated. The overall HC2 HR HPV positivity rate in this age group was 3.9% (confidence interval 2.8-5.3%). When stratified by age group, the rate was inversely proportional to age (ages 30-35: 6.7%; 36-40: 3.0%; 41-45: 2.6%) and lower than most previous reports (1-17%). Some of the cases that were positive for HR HPV by HC2 were negative by LA, or showed only low-risk virus. CONCLUSIONS: The HR HPV rates in women ages 30-45 with a cytologically negative, computer-imaged ThinPrep test result are low. If these findings are confirmed in future studies, the added benefit of HPV testing to liquid-based cytology for women ages 30 and over should be critically evaluated.     

Human papillomavirus testing for primary screening in women at low risk of developing cervical cancer. The Greek experience

OBJECTIVE: To compare the performance of human papillomavirus (HPV) DNA detection against routine Papanicolaou smear for the detection of low- and high-grade cervical intraepithelial neoplasia in a low-risk population. MATERIALS AND METHODS: A cross-sectional study was performed involving 1296 women attending six outpatient clinics in Northern Greece (Thessaloniki, Thermi, Mihaniona, Corfu, Veria, and Serres). Women underwent a gynecological examination, including collection of exfoliated cervical cells for Papanicolaou cytology and HPV DNA detection. Cytology was processed according the conventional routine manner, and HPV DNA was determined using the polymerase chain reaction technique. In positive cases of either method, a complete colposcopic evaluation was performed with directed biopsies. Tests (HPV DNA, cytology, and colposcopy) performance characteristics were determined using the histopathologic diagnosis as the reference standard. RESULTS: HPV DNA testing showed a significantly better sensitivity than the Papanicolaou smear in detecting cervical intraepithelial neoplasia (75% versus 50% for high-grade lesions and 81.2% versus 50% for lesions of any grade, respectively). Specificity, and positive and negative predictive values did not significantly differ. Even after dividing women in younger or older than 30 years, the sensitivity of the HPV DNA test was greater than cytology (100% and 70% versus 50% for cytology in both groups, respectively), with a 6.3% loss in specificity when performed in women younger than 30 years. CONCLUSION: HPV testing could be useful in screening women at low risk for cervical cancer, either as an adjunct tool to augment existing cytology programs or as a unique test of its own.     

Prevalence of human papillomavirus in cervical swabs in the Okinawa Islands,Japan

Although human papillomavirus (HPV) is the main risk factor for invasive cervical cancer, the mechanisms of developing carcinoma are not entirely understood. In particular, the biology and natural history of HPV infection are still unknown. Therefore, we have investigated the incidence of human papillomavirus infection by polymerase chain reaction (PCR) in cervical swabs obtained from women who had cervical cancer screening in three separate areas of the islands of Okinawa. The prevalence of HPV in women aged between 30 and 85 years in the three local areas, Yonashiro-town, Naha-city, and Hirara-city, was consistent (9 to 10%). HPV of various oncogenic types, including HPV16, 18, 31, 33, 35, 35, and 58, were identified in HPV-positive swabs and the prevalence of these types varied in the three areas. Received: 21 August 2001 / Accepted: 18 November 2001 Correspondence to T. Maehama