Persistent High-risk Human Papillomavirus Infection Research Articles

Higher incidence and persistence of high-risk human papillomavirus infection in female sex workers compared with women attending family planning

There are no data on the incidence and persistence of high-risk human papillomavirus (HR-HPV) infections in female sex workers (FSWs). We aimed to describe and compare the rates of incidence and persistence of HR-HPV infections in FSWs and women from the general population (WGP) who attended healthcare facilities between May 2003 and December 2006 in Alicante, Spain. Women with an established HR-HPV infection at study entry were evaluated for the analysis of HR-HPV persistence, and those testing negative for HR-HPV infection at entry were evaluated for the analysis of incidence. HR-HPV infection was determined by the Digene HC2 HR HPV DNA Test. A total of 736 women - 592 WGP and 144 FSWs - were followed for a median of 16.8 months. Global incidence and persistence rates were 3.98 per 100 woman-years (95% confidence interval (CI) 2.91-5.45) and 26.81 per 100 woman-years (95% CI 20.08-35.79), respectively. In the multivariate analysis, only commercial sex work was associated with a statistically significant higher incidence (relative risk (RR) 4.72, 95% CI 2.45-9.09) and persistence (RR 1.93, 95% CI 1.08-3.46) of HR-HPV infection. Our data show that FSWs have both a higher incidence and a higher persistence of HR-HPV than WGP and should be prioritized in HPV-related cancer screening programs.

Risk factors for high‐risk human papillomavirus infection in unscreened Malian women

To investigate the epidemiology of human papillomavirus (HPV) infection in Malian women, for whom cervical cancer is the most common cancer and the second most common cause of cancer-related mortality. Pilot study of 202 women aged 15-65 to determine the prevalence rate of high-risk HPV infection among unscreened Malian women. Information on risk factors was collected through a standardized, structured interview and clinical examination. High-risk (HR) HPV DNA was detected using signal amplification methods (hybrid capture II). High-risk HPV DNA was detected in 12% of unscreened women, while visual inspection after application of acetic acid and Lugol's iodine (VIA/VILI) identified suspicious abnormalities in 2.5% of unscreened women. Histopathological evaluation of VIA/VILI-positive biopsies revealed no evidence of cervical intraepithelial neoplasia or cervical cancer. The majority of infections occurred among women in the 15-24 year old range. Compared to women who were married or widowed, single women were 3.5 times more likely to be infected with HR HPV. The prevalence of infection with cancer causing types of HPV in this study was 12%. These prevalence estimates are consistent with what has been reported previously for other West African countries.

Male Foreskin and Oncogenic Human Papillomavirus Infection in Men and their Female Partners

Persistent high-risk human papillomavirus (HR-HPV) infection causes cervical cancer, the third leading cause of cancer mortality in women worldwide. High rates of HR-HPV and cervical cancer occur in sub-Saharan Africa and are exacerbated by the HIV epidemic, making prevention of HR-HPV and HIV priorities. Male circumcision reduces HIV acquisition in men. As presented in this article, randomized controlled trial data also demonstrate that male circumcision reduces penile HR-HPV infection in both HIV-negative and -positive men. Male circumcision of HIV-negative men also reduces the prevalence and incidence of HR-HPV infections in their female partners. However, male circumcision of HIV-positive men has no effect on HR-HPV infection in their female partners. These data demonstrate that male circumcision is most effective prior to sexual debut, and the presence of the male foreskin facilitates HIV and HR-HPV infection in men and their female partners. Additional studies that utilize the foreskin mucosa obtained at the time of male circumcision are needed to assess the mucosal microenvironment in HIV and HR-HPV coinfections to develop additional preventive and therapeutic approaches.

See-and-Treat Approaches to Cervical Cancer Prevention for HIV-Infected Women

Cervical cancer remains the second commonest cancer among women worldwide, and more than 85% of the global burden of this disease occurs in the developing world. HIV-infected women have a higher likelihood of developing persistent high-risk human papillomavirus (HPV) infection, precancer, and invasive cervical cancer than seronegative women. Although highly effective primary and secondary prevention strategies are currently available, they remain inaccessible to the vast majority of women. Because of their simplicity and affordability, see-and-treat cervical cancer screening modalities have the potential to substantially improve women's access to cancer prevention, as well as to create much needed infrastructure for future molecular-based cervical screening and HPV vaccination programs. Additional data addressing the effectiveness of see-and-treat approaches for HIV-infected women are urgently needed. Studies informing best practice guidelines on when to start, when to stop, and how frequently to screen HIV-infected women within the see-and-treat paradigm would be of great value.

Risk estimates for persistent high-risk human papillomavirus infections as surrogate endpoints of progressive cervical disease critically depend on reference category: analysis of the combined prospective cohort of the New Independent States of the Former Soviet Union and Latin American Screening Studies

To make feasible future clinical trials with new-generation human papillomavirus (HPV) vaccines, novel virological surrogate endpoints of progressive disease have been proposed, including high-risk HPV (HR-HPV) persistence for six months (6M+) or 12 months (12M+). The risk estimates (relative risks [RRs]) of these 'virological endpoints' are influenced by several variables, not yet validated adequately. We compared the impact of three referent groups: (i) HPV-negative, (ii) HPV-transient, (iii) HPV-mixed outcome on the risk estimates for 6M+ or 12M+ HR-HPV persistence as predictors of progressive disease. Generalized estimating equation models were used to estimate the strength of 6M+ and 12M+ HR-HPV persistence with disease progression to squamous intraepithelial lesions (SILs), cervical intraepithelial neoplasia (CIN) grade 1+, CIN2+, CIN/SIL endpoints, comparing three optional reference categories (i)-(iii) in a prospective sub-cohort of 1865 women from the combined New Independent States of the Former Soviet Union (NIS) and Latin American Screening (LAMS) studies cohort (n = 15,301). The RRs of these viral endpoints as predictors of progressive disease are affected by the length of viral persistence (6M+ or 12M+) and the surrogate endpoint (SIL, CIN1, CIN2, CIN/SIL). Most dramatic is the effect of the referent group used in risk estimates, with the HPV-negative referent group giving the highest and most consistent RRs for both 6M+ and 12M+ viral persistence, irrespective of which surrogate is used. In addition to deciding on whether to use 6M+ or 12M+ persistence criteria, and cytological, histological or combined surrogate endpoints, one should adopt the HPV-negative referent group as the gold standard in all future studies using viral persistence as the surrogate endpoint of progressive disease.

A pilot study to investigate the treatment of cervical human papillomavirus infection with zinc-citrate compound (CIZAR®)

Objective In the present study the potential therapeutic effects of zinc-citrate compound (CIZAR®) in women infected with high-risk human papillomavirus (HR-HPV) was investigated. Methods A total of 194 women diagnosed with HR-HPV infection using the Hybrid capture (HC) II assay with no evidence of high grade squamous intraepithelial lesions (HSIL) or worse by Pap smear and colposcopy were enrolled. Among them, 76 women were treated by twice weekly self administered intra-vaginal infusion of 0.5 mM zinc citrate solution containing CIZAR® for 12 weeks and were evaluated for clearance of the HR-HPV infection compared to 118 women without treatment (Control group). Results The 12 weeks zinc citrate solution treatment resulted in the elimination of HR-HPV in 49/76 (64.47%) patients compared to the spontaneous clearance of 15.25% (18/118) in the control group ( p = 0.000). By logistic regression analysis, the 12 week zinc citrate solution treatment reduced the risk of persistent HR-HPV infection significantly (OR 0.079; 95% CI 0.039-0.165; p = 0.000). Conclusion The results of this study showed for the first time that treatment with intra-vaginal infusion of a zinc-citrate compound (CIZAR®) can result in elimination of HR-HPV infection from the uterine cervix.

Prevalence and Risk Factors of Human Papillomavirus (HPV) Infection in Southern Chinese Women – A Population-Based Study

BackgroundPersistent high-risk type Human papillomavirus (HPV) infection is recognized as a necessary cause of cervical cancer. This study aimed to compare the HPV prevalence and risk factors between women residing in Hong Kong (HK) and Guangzhou (GZ) region of China.Methodology/Principal FindingsA total of 1,570 and 1,369 women were recruited from HK and GZ, respectively. The cytology samples were collected and tested for HPV infection. The overall and type-specific HPV prevalence and the potential risk factors for acquisition of HPV infection were studied. Women with normal cytology in the GZ cohort had significantly higher HPV prevalence (10%) than those in the HK cohort (6.2%, p<0.001). The patterns of the age-specific HPV prevalence were also different between the two cohorts. In the HK cohort, women at the age of 20–29 years old had the highest prevalence and a second peak was observed in the age of ≥60 years old. In the GZ cohort, the highest HPV prevalence was also observed in 20–29 years old but declined as the age increased and a second peak was not seen. HPV16 and HPV52 were the most common high-risk types found in the HK and GZ cohorts, respectively. Age was the most consistently observed independent risk factor for HPV infection in the HK, while the number of sexual partners had association in the GZ cohort.Conclusions/SignificanceOur study provides the current status and the epidemiological characteristics of HPV prevalence in Southern Chinese women. The results strongly suggested that population education and the effective cervical cancer screening would be vital in the prevention of cervical cancer.

Abstract 4780: c-FLIP knockdown increases apoptosis in cervical cancer cell lines

Abstract Cervical Uterine cancer is a leading cause of cancer deaths in women worldwide. Its natural history begins gradually from low-grade and high-grades squamous intraepithelial lesions to an invasive disease. Decades of studies have confirmed a directly association between persistent high-risk Human Papillomavirus (HPV) infections and cervical cancer. However, high-risk HPV infections are not sufficient to induce cellular transformation and tumor occurrence. The cellular FLICE-like inhibitory protein (c-FLIP) has been founded overexpressed in several cancers and could be associated with cervical carcinogenesis. c-FLIP is a catalytically inactive caspase-8/-10 homologue, and when is overexpressed has the ability to inhibit the extrinsic pathway of apoptosis. Aim: To characterize c-FLIP participation in cervical carcinogenesis.Materials and Methods: Four cell lines were used in this study: ECT1 E6/E7 (squamous normal cervical epithelial), SiHa (cervical carcinoma containing an integrated HPV 16 genome), C-4I (cervical carcinoma containing an integrated HPV 18 genome) and C-33A (cervical carcinoma without HPV). c-FLIP expression in cell lines was determined by real time PCR and western blot. c-FLIP expression was transiently downregulated by siRNA directed against c-FLIP mRNA and the silencing effects on cell viability and apoptosis were analysed, by comparing with a control negative siRNA-transfected cells.Results: c-FLIP was found to be overexpressed in SiHa and C-4I cell lines and repressed in C-33A cell line. Only the long variant of c-FLIP was found in cervical cancer cell lines. Transient knockdown of c-FLIP resulted in significant reduction in cell viability (p&amp;lt; 0.001), compared with negative control siRNA-transfected cells. Knockdown cells lines exhibited an increased apoptotic rate in comparison with controls (p&amp;lt;0,001). Conclusions: The long variant of c-FLIP is overexpressed in cervical cancer cell lines with integrated genome of a high-risk HPV. Furthermore, the siRNA-mediated downregulation of c-FLIP expression induces apoptosis and decreases cell viability in cervical cancer cell lines. Therefore, this protein could be a potential therapeutic target in cervical cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4780. doi:10.1158/1538-7445.AM2011-4780

Risk factors for squamous intraepithelial lesions in systemic lupus erythematosus: A prospective cohort study

We undertook a prospective cohort study to ascertain the risk factors for the development of squamous intraepithelial lesions (SIL) in patients with systemic lupus erythematosus (SLE). One hundred thirty-seven SLE patients with a normal Papanicolaou (Pap) smear at baseline were evaluated at 6-month intervals for up to 3 years. At each visit, a Pap smear, human papillomavirus (HPV) DNA test, and clinical assessment were performed. Among the 137 patients, there were 12 incident cases (8.8%) of SIL over a median followup duration of 30.7 months (interquartile range 25.5-31.7). Among the 30 patients with HPV infection detectable by DNA testing at baseline, 9 (30%) developed SIL. The independent risk factors for the incident SIL in this group of SLE patients included the use of cyclophosphamide (CYC) ever (odds ratio [OR] 5.6, 95% confidence interval [95% CI] 1.1-29.3; P=0.041) and persistent high-risk HPV infection (OR 26.9, 95% CI 3.2-222.3; P=0.002). The use of baseline HPV testing has a higher sensitivity than abnormal cytology (defined as atypical squamous cells of undetermined significance; 47.7% versus 33.3%) in predicting the development of SIL. Independent risk factors associated with the development of SIL in SLE patients included persistent high-risk HPV infection and the use of CYC. Low-risk patients who receive negative test results on both cervical cytology screening and HPV DNA testing may not need to be rescreened within 3 years.

Abstract B77: High-risk human papillomavirus genotypes among HIV-negative black women with or without cervical disease in South Africa

Abstract Objective: Persistent high-risk human papillomavirus (HPV) infections are associated with cervical pre-malignant lesions and cervical cancer. Women in sub-Saharan Africa are at high risk of advanced cervical disease as well as cervical cancer. We examined the prevalence and distribution of high-risk HPV types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 66) among HIV-negative Black women enrolled in three cervical cancer screening studies in Cape Town, South Africa. Knowledge of the epidemiology of high-risk HPV types in this population will help target prevention interventions. Methods: Black women, aged 17-65 years, were tested for high risk HPV DNA using the Hybrid Capture 2 (HC2) assay and positive samples were typed by PCR to determine the specific genotype. Cervical disease status was determined by colposcopy and cervical biopsy. The prevalence and distribution of high-risk HPV types as well as the frequency of multiple high-risk HPV types were examined by age and cervical disease. Results: Among 8,073 HIV-negative women included in the study, 20.9% (n=1689) were HC2 HPV DNA positive; and, in 73.62% (n=1223/1661) of these positives, a specific high-risk HPV type was detected. Overall, the prevalence of high-risk types was 19.94%. The most common high-risk types across cervical disease status were HPV 16 and 35. Among women without cervical disease, younger women, aged 17-29 years, had the highest prevalence of high-risk types in comparison to older women. Among women with CIN 2 or CIN 3, a higher prevalence of HPV 16 and 45 was observed among older women, aged 40-65 years, than among younger women, aged 17-29 years; as for HPV 35, the prevalence was stable across age groups. The distribution of HPV 16, 35, and 33 were statistically significantly higher among HC2 DNA positive, high-risk HPV positive women with advanced cervical disease than women with no cervical disease or CIN 1 (p-values &amp;lt; 0.02). Younger women, aged 17-29 years, had more multiple types overall and across all cervical disease status than older women, aged 40-65 years. Conclusion: HPV 16 and 35 are the leading contributors of cervical disease among HIV-negative Black South African women. Therefore, the HPV vaccine has the capacity to result in significant reduction in HPV-related cervical disease in this population. Citation Information: Cancer Prev Res 2010;3(12 Suppl):B77.

Knowledge of HPV and cervical cancer among HIV-positive women in Lagos, Nigeria

Background Cervical cancer is the second most common cancer among women in the world. In parts of Africa it is the most common cancer among women. The age-specific incident rate is in some parts of Africa. Persistent infection with high-risk human papillomavirus (HPV) is a necessary cause of cervical cancer and HIV is a known co-factor that enhances the oncogenic potential of HPV. Sub-Saharan Africa has the highest number of people living with HIV. In Nigeria there are about 4.5 million people living with HIV/AIDS; more than half are women. Women infected with HIV are at greater risk of persistent HPV infection and consequently at greater risk of the associated premalignant disease and cervical cancer. The objective of this study was to determine the knowledge of HIV-positive women on HPV and cervical cancer.

Long-term Absolute Risk of Cervical Intraepithelial Neoplasia Grade 3 or Worse Following Human Papillomavirus Infection: Role of Persistence

Infection with high-risk human papillomavirus (HPV) is the main cause of high-grade cervical intraepithelial neoplasia (CIN) and cancer. It has been suggested that information about high-risk HPV type-specific infection might make cervical cancer screening more effective. Persistent HPV infection could also be a useful screening marker. We estimated the long-term risk of high-grade CIN after one-time detection of high-risk HPV DNA and after persistent infection with individual high-risk HPV types. A cohort of 8656 women from the general population of Denmark was examined twice, 2 years apart (first study examination: May 15, 1991, to January 31, 1993; second study examination: October 1, 1993, to January 31, 1995). The women underwent a gynecological examination and cervical cytology and had swabs taken for HPV DNA analysis by the Hybrid Capture 2 and line probe assays. The women were followed up through the nationwide Danish Pathology Data Bank for cervical neoplasia for up to 13.4 years. The absolute risk of developing cervical lesions before a given time was estimated as a function of time. For women with normal cytological findings who were concurrently HPV16 DNA positive at the second examination, the estimated probability of developing CIN grade 3 (CIN3) or worse within 12 years of follow-up was 26.7% (95% confidence interval [CI] = 21.1% to 31.8%). The corresponding risks among those infected with HPV18 was 19.1% (95% CI = 10.4% to 27.3%), with HPV31 was 14.3% (95% CI = 9.1% to 19.4%), and with HPV33 was 14.9% (95% CI = 7.9% to 21.1%). The absolute risk of CIN3 or worse after infection with high-risk HPV types other than HPV16, HPV18, HPV31, or HPV33 was 6.0% (95% CI = 3.8% to 8.3%). The estimated absolute risk for CIN3 or cancer within 12 years of the second examination among women who were HPV16 DNA positive at both examinations was 47.4% (95% CI = 34.9% to 57.5%); by contrast, the risk of CIN3 or worse following a negative Hybrid Capture 2 test was 3.0% (95% CI = 2.5% to 3.5%). HPV16, HPV18, HPV31, and HPV33 infection and especially HPV16 persistence were associated with high absolute risks for progression to high-grade cervical lesions. The results indicate the potential value of genotyping in cervical cancer screening. Given that HPV DNA-negative women retained their low risk of CIN3 or worse for many years, frequent screening of these women may be unnecessary.

A pilot study of HPV DNA and cytology testing in 50,159 women in the routine Mexican Social Security Program

We present a large feasibility evaluation of high-risk HPV (HR-HPV) DNA testing and cervical cytology as a primary screening strategy for cervical cancer precursor lesions in Mexican women, as part of a routine cancer control program (CCP). A community-based study was carried out in 50,159 women aged 20-70years who visited the CCP in 12 federal entities located in Northern, Central, and Southern Mexico, including a total of 48 primary health care units of the Instituto Mexicano del Seguro Social (IMSS). Cervical specimens for cytology and HR-HPV tests were collected at baseline. Women with cytological abnormalities (ASCUS or greater) were referred to colposcopy for further evaluation and treatment if necessary. A subset of HR-HPV-positive women without cervical lesions, in Morelos state, were tested again for HR-HPV DNA within a year, and repeat-positive women were referred to colposcopy. HR-HPV prevalence among all women was 8.6% (95% CI: 8.3-8.9). Prevalence by age group was 12.2% (95% CI: 11.0-13.3) before 30years of age and decreased to 7.4% (95% CI: 6.7-8.0) between 46 and 50years of age. A second minor prevalence peak (8.1%; 95% CI: 7.2-9.0) was observed in women more than 55years of age. Overall prevalence of cytological abnormalities was relatively low (2.2%; 95% CI: 2.0-2.3) with the highest frequency of abnormal cytology (ASCUS or greater) in the 41-45year age group (2.5%: 95% CI 2.1-2.7). No correlation between cervical abnormalities and HR-HPV prevalence, by region, was observed. A total of 370 (0.7%) women had an abnormal cytology as well as a positive HR-HPV result; 736 (1.5%) had an abnormal cytology and a negative HR-HPV test; 3,941 (7.9%) women had a positive HR-HPV test and a normal cytology; and 45,112 (89.9%) women were negative in both tests. The first two groups were immediately referred to colposcopy, 72.7% of the women from the cytology-positive and HR-HPV-positive group and 58.0% from the cytology-positive and HR-HPV-negative group successfully completing evaluation. Among the 269 cytology-positive and HR-HPV-positive women, 53 (19.7%) CIN2/3+ cases were detected, whereas among the 427 cytology-positive and HR-HPV-negative participants, only 13 (3.0%) CIN2/3+ cases were documented. In Morelos state, a sample of 287 women with a negative cytology smear and a positive HR-HPV test at baseline were re-screened after ~12months, by means of cytology and HR-HPV testing. Among these women, 106 (36.9%) were again HR-HPV positive and were referred to colposcopy. Of whom, 76 (71.7%) were successfully evaluated; among these women, 9 CIN2/3+ (11.8%) were documented. Sensitivity of cervical cytology for detecting histologically confirmed CIN2/3+ cases was only 40.0% (95% CI 38.5-41.4) compared to 93.3% (95% CI 92.5-94.0) for HPV DNA testing considering the additional cases detected among women with persistent HPV infection. The specificity of cytology was 97.0 vs. 89.2% for the HPV DNA test. Population-based programs using HR-HPV testing can improve cervical cancer prevention and control in Mexican and other populations where cytological screening is inadequate for detecting precursors of cervical cancer.

Association Between Serum Cytokine Profiles and Clearance or Persistence of High-Risk Human Papillomavirus Infection: A Prospective Study

The cytokines that may be associated with the clearance or persistence of high-risk human papillomavirus (HPV) infection in patients with mild dysplasia or less of the uterine cervix were determined. A prospective study of 160 patients who harbored high-risk HPV with histologically confirmed mild dysplasia or less between January 2006 and August 2008 was performed. All patients were followed up at every 4 months during the first year. Human papillomavirus DNA tests by the Hybrid Capture 2 method (Digene, Gaithersburg, Md) were performed at every visit on all patients. Blood sampling was performed in all patients at their initial visit, and an enzyme-linked immunosorbent assay was used to measure the serum levels of interferon gamma, tumor necrosis factor alpha, and interleukins 6 and 10. Of the 160 patients, 107 (66.9%) had clearance of HPV infection after 12 months of follow-up. The median age of patients in the persistence group was significantly higher than that of patients in the clearance group (47 vs 38 years, respectively; range, 21-77 vs 21-71 years, respectively; P = 0.0009). In univariate analysis, the number of patients with serum negative for tumor necrosis factor alpha was significantly higher in the clearance group than the persistence group (P = 0.0363). However, in multivariate logistic regression analysis, all 4 cytokines failed to show any significant association with the clearance or persistence of HPV infection. The baseline serum cytokine levels were not associated with the clearance or persistence of HPV infection. Systemic immunity may not influence the natural history of HPV infection.

Human papillomavirus testing and cervical cytology in primary screening for cervical cancer among women in rural China: Comparison of sensitivity, specificity, and frequency of referral

The causal relationship between persistent high-risk human papillomavirus infection and cervical cancer is widely accepted. HR-HPV DNA testing, alone or in combination with Pap smear testing, may have a role in primary screening. The screening results (VIA, VILI, Pap, and HR-HPV DNA) of 9,057 women in rural China were analyzed to determine the screening performance for the detection of CIN3+. All screening strategies had comparable AUCs (0.9). Cotesting strategies had the overall highest sensitivity for CIN3+ (99.4%), followed by HR-HPV DNA testing alone (96.3%), Pap alone (80.2%), and reflex testing (75.4%). Reflex testing had the highest specificity (96.7%), followed by Pap alone (93.3%), HR-HPV DNA testing alone (85.5%), and both cotesting strategies (LSIL: 84.8%, HSIL: 84.8%). Of the single-test strategies, HR-HPV DNA testing had a higher sensitivity (96.3% vs. 80.2%) compared with Pap testing. The specificity of the Pap test was higher (93.3% vs. 85.5%) and it had a lower percent referred for colposcopy (7.8% vs. 15.8%) than HR-HPV DNA testing. HR-HPV DNA testing with a 10.0 cutoff point (relative light units/cutoff ratio) had a sensitivity (85.2%) and specificity (90.6%) estimate comparable to Pap testing. A single-test primary screening strategy with adequate performance would permit less frequent screening and be most appropriate. Of the primary screening strategies investigated in this setting in China, the performance of HR-HPV DNA testing with an increased cutoff-point might best meet these criteria.

Natural history of infections with high-risk HPV in Chinese women with abnormal cervical cytology findings at baseline

Objective To clarify the natural history of disease in Chinese women with benign cytologic observation and positive for high-risk human papillomavirus (HR-HPV). Method From September 1, 2004, to June 30, 2008, this prospective study followed up 893 women positive for HR-HPV who also had benign cytologic findings at baseline. Results After 3 to 57 months, the viral clearance rate was higher for patients younger than 30 years and for patients who had a low viral load at baseline than for those in their comparison groups. Conversely, the occurrence rate of cervical intraepithelial neoplasia (CIN) 2 or 3 was higher for patients with persistent HR-HPV infection, those who had CIN 1 at baseline, and those whose the second viral load was increased. Conclusion Age, viral load, and presence of CIN 1 at the first evaluation were the main factors affecting the natural history of HR-HPV infection in women with benign baseline cytologic findings. The result(s) of the second HR-HPV testing were independent indicators of histologic progression.

Persistence of high‐risk human papillomavirus infection in a population‐based cohort of Danish women

Persisting human papillomavirus (HPV) infection is a critical step in cervical carcinogenesis. This study was conducted to determine the type-specific HPV persistence and risk factors for persistence of high-risk HPV infections in a large cohort of Danish women. The study was based on a population-based prospective cohort study of women aged 20-29 years. Participants were interviewed and underwent two gynecological examinations 2 years apart. Women with Hybrid Capture 2 results at enrolment and a follow-up visit were included in the analysis (n = 7,418). Persistence was defined as positivity for the same high-risk HPV type at both examinations. Overall, 4.2% of the women had persistent HPV infection, accounting for 26.9% of the initially HPV-positive women. HPV 16, HPV 58, and HPV 31, all from species group alpha 9, were the most persistent types; however, other high-risk HPV types that are detected rarely in cancer cases were also likely to persist. The number of high-risk HPV types and detection of HPV 16 infection at baseline and ever use of oral contraceptives increased the risk for persistence. The risk factor analyses also showed that use of an intrauterine device decreased the risk for persistent high-risk HPV infection among women with one high-risk HPV type at baseline. No association was found with viral load or smoking. In conclusion, persistent high-risk HPV infection, especially HPV 16 persistence, was common among women positive for high-risk HPV.

Clearance of human papillomavirus infection after successful conization in patients with cervical intraepithelial neoplasia

The natural history of high-risk human papillomavirus (HRHPV) infection after successful treatment of cervical intraepithelial neoplasia (CIN) is not well known. This study was performed to evaluate the rate and pattern of HRHPV infection clearance after successful conization for CIN and to analyze factors associated with such clearance. A total of 287 patients who underwent loop electrosurgical excision procedures (LEEP) owing to HRHPV-associated CIN were included. All patients had negative resection margins on LEEP specimens and underwent HPV testing with the hybrid capture II system at 3-, 6-, 9-, 12-, 18- and 24-month follow-up visits after LEEP. Persistent HPV infections were detected in 45.6%, 14.3%, 6.3%, 2.2%, 1.5% and 1.1% of patients at 3, 6, 9, 12, 18 and 24 months after LEEP, respectively. Clearance rates did not differ by age, parity or severity of cervical lesion. However, clearance rates were significantly slower in patients with HPV DNA loads >500 RLU/PC before LEEP (p = 0.040). During 2 years of follow-up after LEEP, 24 patients had recurrent disease revealed by biopsy. The odds ratios for recurrent disease in patients with persistent HRHPV infection increased gradually from 5.17 at the 3-month follow-up visit to 12.54, 15.69 and 25.90 at 6-, 9-, 12- and 24-month follow-up visits, respectively. We conclude that HRHPV infection cleared gradually in most patients within 6 months of treatment. Clearance rates were significantly slower in patients with HPV DNA loads >500 RLU/PC. Persistent HPV infection was a significant positive predictor of recurrence.

Self-sampling of the vaginal fluid at home combined with high-risk HPV testing

Background:Around 65% of women with cervical carcinoma in Sweden have not attended an organised screening. We therefore investigated the value of using self-sampling at home in combination with a test for high-risk human papilloma virus (HPV) to increase participation.Methods:A total of 2829 women 30–58 years old, who had not attended the organised screening for ⩾6 years, were recruited. They were offered self-sampling at home (Qvintip) and recommended to send the collected vaginal fluid to a laboratory for analysis of the presence of high-risk HPV (Hybrid Capture 2 method).Results:A total of 39.1% of the women accepted home sampling. These women disclosed a relatively high prevalence of high-risk HPV, which decreased with age, from 11.1% in women 30–39 years old to 2.9% in women ⩾50 years . Follow-up disclosed histological cervical intraepithelial neoplasm (CIN) 2–3 lesions in 43.2% of the women with a persistent HPV infection, corresponding to 2.0% of the total number of participating women. The sensitivity of a single smear to detect the histological CIN 2–3 lesions were only 52.6%, even if all abnormal smears (atypical squamous cells of unknown significance (ASCUS)–CIN 3)) were included.Conclusion:The use of self-sampling at home in combination with testing for high-risk HPV increases the participation rate of the organised screening and detects almost twice as many women with pre-malignant cell alterations (CIN 2–3) in comparison those with a single cytological smear.

Natural history of persistent high-risk human papillomavirus infections in Korean women

ObjectiveThis prospective study was performed to evaluate the clearance of high-risk human papillomavirus (HPV) infection and incidence of cytologic abnormality and cervical intraepithelial neoplasia (CIN) during the follow-up of persistent infection in Korean women. MethodsA total of 4170 women who were screened for cervical cancer, were aged 30 years or older, had no abnormal last Pap smear results for 3 years, had no history of treatment for cervical neoplastic disease, and were not pregnant were analyzed for high-risk HPV prevalence using the Hybrid capture (HC) II assay. The 224 women with normal cytology but positive for high-risk HPV DNA using the HC-II assay were analyzed for their clearance of HPV infection. ResultsThe median time to clearance in women with initially normal cytology was 7.5 months from initial detection (95% CI, 5.2–9.8 months). There were significant differences in the median time to clearance (4.5 vs. 14.5 months, p <0.001) of high-risk HPV infection between women with the initial relative light unit/ cutoff (RLU/CO) ratio values <10.0 and ≥10.0, as determined by the HC-II assay. In Kaplan–Meier analysis, probability of development of cytologic abnormalities, CIN and high-grade CIN was 38.2%, 21.7% and 8.5% respectively at 24 months of persistent high-risk HPV infection. ConclusionThe prevalence and clearance of high-risk infection in Korean women was similar to that in Western countries. Persistent high-risk HPV infection was associated with high viral load.