Human Papillomavirus DNA Test Results Research Articles

The Epidemiology of Anal Human Papillomavirus (HPV) in HIV-Positive and HIV-Negative Women and Men: A Ten-Year Retrospective Observational Study in Rome (Italy).

Human papillomaviruses (HPVs) commonly infect the anogenital mucosa; most infections are transient, but a fraction of those caused by high-risk (HR) types persist and may lead to anogenital cancer. The epidemiology of HPV genotypes in anal infections in groups at different risk for anal cancer has not been well described in Italy. This retrospective study reports the results of HPV DNA testing and complete genotyping performed on anal swabs from 691 female and male patients attending proctology clinics in Rome during 2012-2021; one-third had repeated testing. Cumulative HPV positivity in 1212 anal swabs was approximately 60%, was not age related, and showed an increasing trend over the study period. HPV rates differed significantly by sex and HIV status: HIV-negative women had the lowest (43.6%) and HIV-positive men the highest (83.5%) HPV prevalence. HIV-positive men had more oncogenic HPV genotypes detected, more multiple infections, and the highest frequency of persistent infections. Two-thirds of all infections were vaccine-preventable. This study found that anal HPV infection rates are still elevated and even increasing in groups at low and high risk of developing anal cancer. Prevention programs need to be improved to reduce rates of anal infection in young women and men.

Liquid-Based Cervical Cytology: Monitoring the Laboratory Quality Indicators.

Many developments in cervical cancer screening have happened in the past century, helping women in earlier detection of cervical cancer and its precursors. Cytology still holds the fort as being a specific test, though it suffers in sensitivity. As a part of the quality control program, the aim of the study is to determine the total number of abnormal liquid-based cervical cytology (LBC) at our center and correlate the abnormal LBC with histology and human papillomavirus (HPV) DNA test results. Retrospective analysis of 4286 LBC screening cases was carried out over a period of 5 years. For cytology-histology correlation, cervical biopsy and cytology test results were analyzed. The two-tier grading system for biopsy interpretation was used. HPV DNA test results wherever available were correlated. Of the 4286 LBC cases, 157 samples (3.7%) were unsatisfactory for evaluation, 3915 samples (91.3%) were negative for intra-epithelial lesion or malignancy, and 214 samples (5%) showed epithelial cell abnormality. ASC-US was reported in 60 cases (1.4%), ASC-H in 35 cases (0.8%), LSIL in 47 cases (1.1%), HSIL in 41 cases (1.0%), squamous cell carcinoma in a single case (0.02%), and atypical glandular cells in 30 cases (0.7%). The ASC/SIL ratio was 1.07:1. The CHC major discrepancy was calculated as 16.2%. The concordance of HSIL on cytology and biopsy as a measure of PPV is 94.4%. Of the epithelial cell abnormalities, 24 cases were positive for high-risk HPV (hrHPV). Molecular test results of 2737 samples showed HPV detected in 50 cases, of which 24 cases were positive for hrHPV. The study helped us to analyze the quality parameters of our cytopathology laboratory which are within the acceptable limits.

High-grade vulvar intraepithelial neoplasia: comprehensive characterization and long-term vulvar carcinoma risk.

Adequate diagnosis of human papillomavirus (HPV)-associated high-grade squamous intraepithelial lesion (HSIL) and HPV-independent vulvar intraepithelial neoplasia (VIN) is essential but can be challenging. We comprehensively characterized a large population-based series of vulvar lesions, originally reported as high-grade VIN, and assessed the cancer risk. Baseline high-grade VIN of 751 patients were categorized by histopathological reassessment, integrating the results of immunohistochemistry (p16INK4a , p53, Ki-67) and HPV DNA testing. Integrated analyses resulted in 88.4% HPV-associated lesions (77.0% HSIL, 10.9% low-grade SIL [LSIL], and 0.4% vulvar squamous cell carcinoma [VSCC]), 10.9% HPV-independent lesions (6.1% HPV-independent VIN, 4.7% nondysplastic lesions, and 0.1% VSCC) and 1.1% inconclusive lesions. HSIL demonstrated p16INK4a block-positivity in 99.0%, increased Ki-67 in ≥2/3rd of the epithelium in 93.6%, and HPV positivity in 99.6%. In HSIL, a p53 wildtype mid-epithelial staining pattern was common (51.6%) while this was not observed in HPV-independent lesions. HPV-independent VIN harboured mutant p53 patterns in 65.2% and showed a wide morphological spectrum, ranging from differentiated to nondifferentiated ('HPV-associated-like', in 41.3%). Kaplan-Meier analyses showed a 10-year cancer risk of 8.0% in HPV-associated HSIL, 67.4% in HPV-independent VIN/p53mutant, and 27.8% in HPV-independent VIN/p53wildtype. Strikingly, the 10-year cancer risk was 73.3% in HPV-independent VIN with nondifferentiated ('HPV-associated-like') morphology. Immunohistochemistry by p16INK4a and p53 is highly recommended for optimal categorization into HPV-associated and HPV-independent VIN, which is of utmost importance given the different cancer risk. The high cancer risk of HPV-independent VIN underscores the need for surgical treatment and close follow-up, especially in case of a p53 mutant pattern and/or nondifferentiated morphology.

Human papillomavirus genotyping predicts residual/recurrent disease after local treatment for cervical intraepithelial neoplasia better than viral DNA testing.

Type-specific persistent infection (TSPI) of human papillomavirus (HPV) is reportedly associated with a high risk of residual/recurrent disease after local treatment for cervical intraepithelial neoplasia (CIN). This study aimed to evaluate whether HPV genotyping is more accurate in detecting residual/recurrent disease than HPV DNA testing and identify which HPV genotype can predict a high risk of residual/recurrent disease. We retrospectively reviewed patient outcomes and results of HPV DNA testing and genotyping at 6-12 months after local treatment for CIN2/3 for 439 women. We investigated residual/recurrent disease occurrence according to the TSPI and new infections. Sensitivity, specificity, and positive and negative predictive values (PPV and NPV, respectively) of the two testing methods for predicting residual/recurrent diseases were also evaluated. Eighty-five (19.4%) patients were positive for HPV DNA testing after treatment, of which 74 (87.1%) had TSPI. Residual/recurrent disease was identified in 34 (7.7%) patients, of which 30 were positive for HPV DNA testing and had TSPI of HPV16, 18, 31, 33, 52, and 58 (six HPV genotypes). The sensitivity and NPV of HPV DNA testing and TSPI were equal at 88.2% and 98.9%, respectively. The specificity and PPV of TSPI were higher than those of HPV DNA testing (89.1% vs. 86.4%, 40.5% vs. 35.2%, respectively). Furthermore, the TSPI of the six HPV genotypes further improved specificity (90.6%) and PPV (44.1%) with the same sensitivity and NPV. HPV genotyping is more useful than HPV DNA testing for determining TSPI, especially of the six HPV genotypes.

Human Papillomavirus (HPV) DNA Detection Using Self-Sampling Devices in Women Undergoing Long Term Immunosuppressive Therapy.

Immunosuppression is a risk factor of persistent human papillomavirus (HPV) infections, which might lead to development of (pre)malignant lesions of the cervix and lower anogenital tract. Results of HPV DNA testing using cervicovaginal self-samples are comparable to those that are clinician-obtained and therefore might be used in cervical screening. The aim of this study was to assess the prevalence of high-risk HPV (hrHPV) infections, their risk factors and the genotypes distribution among women undergoing immunosuppressive therapy. Women undergoing immunosuppressive therapy for at least three months due to solid organ transplantation or autoimmune disorders were asked to self-collect samples for HPV testing using cervicovaginal brushes and complete questionnaires regarding cervical cancer risk factors. HPV DNA detection and genotyping were performed using Genotyping kit HPV GP version 2. hrHPV was detected in 26/90 (28.9%) specimens. Genotyping revealed a broad range of hrHPV, with type 16 being the most common genotype (11/26). The components of bivalent/quadrivalent or nonavalent vaccines cover all genotypes present in 4.4% and 17.8% women, respectively, and occur as a co-infection with other types in 12.2% and 23.3% of women, respectively. The only feature significantly associated with being hrHPV-positive was having at least two lifetime sexual partners. The high prevalence of hrHPV infections among immunosuppressed women emphasizes the need for regular cervical cancer screening with HPV DNA testing, which might be performed on self-collected specimen.

Dynamics of HPV viral loads reflect the treatment effect of photodynamic therapy in genital warts

Photodynamic therapy (PDT) has demonstrated good clinical cure rates and low recurrence rates in the treatment of genital warts. Human papillomavirus (HPV) genotypes and viral load assays can reflect the status of persistent or latent infection and serve as a predictor of infection clearance. Specimens from 41 patients with HPV infection were obtained, and the HPV genotypes and viral load were analyzed using real-time polymerase chain reaction (PCR) assays. Traditional treatment, such as radiofrequency, microwave, or surgical therapy, was used to remove the visible lesions, and then PDT treatment was performed every week. HPV DNA testing was performed at every patient visit and the frequency of PDT treatment was determined by changes in HPV viral loads. HPV viral loads decreased significantly after PDT treatment. There were significant differences in HPV viral loads between pretherapy and three or six rounds of PDT treatment. Significant differences were also observed between single and multiple type HPV infection after six rounds of PDT treatment. Patients with single type HPV infection had significantly higher rates of negative HPV DNA test results, as compared with patients with multiple infections after six rounds of PDT treatment; however, there was no difference in recurrence rates between the two groups. Dynamic monitoring of HPV genotypes and viral loads can be used to guide PDT treatment and indicate PDT treatment efficacy in eliminating HPV.

Concordance of Penile and Oral Human Papillomavirus Infections Among Men in the United States

This study examined the concordance of penile and oral human papillomavirus (HPV) infections in the United States. A total of 1683 men aged 18-59 years who participated in the 2013-2014 National Health and Nutrition Examination Survey and had results of oral and penile HPV DNA testing were examined. The prevalence of any HPV genotype was 45.3% on the penis, 11.2% in the oral cavity, and 8.8% at both sites. The prevalence of HPV in the oral cavity was higher among those with than among those without penile HPV infection (19.3% vs 4.4%; prevalence ratio, 4.37 [95% confidence interval, 2.66-7.16]). The prevalence of ≥1 genotype-concordant HPV infection was 3.2% and was associated with sexual behavior, independent of demographic characteristics and smoking status. Sexual behavior may partly explain the observed association between penile and oral HPV infections.

Investigation of Transition Types of HPV DNA Test Results over Time in Korean Women.

Understanding the history of human papilloma virus (HPV) infection is important for interpretation of a positive HPV DNA screening test, future work-up and treatment. We investigated the transition of HPV DNA test results in Korean women, and analyzed the association of cytology result with transition type. We retrospectively reviewed annual HPV DNA test results for 5,274 subjects between January 2005 and December 2012. Each subject had a minimum of five annual tests over the eight-year period. Based on the pattern of results, the transition type for each subject was assigned to one of the following: negative, persistent, latent, transient, and unclassifiable. Associations of cytology results with the HPV DNA transition types, number of positive results, and the durations of positive results were also analyzed. The proportion of abnormal cytology findings decreased in the following order of transition patterns: persistent, latent, transient, and negative. Among transient patterns, a duration of three years or more significantly correlated with cytology results of non-high grade squamous intraepithelial lesion (HSIL; p<0.001). In the persistent group, duration of five years or more correlated with both non-HSIL and HSIL (p<0.001). Latent group showed no correlation with duration. Irrespective of patterns, having five or more positive results was significantly associated with HSIL (p<0.001). Our findings may contribute to better understanding of HPV infection, interpretation of HPV DNA screening results, and prediction of prognosis according to transition type.

Liquid-based cytology and HPV DNA testing using intra-anal specimens from HIV-negative women with and without genital HPV-induced lesions.

Screening for anal cancer using cytology has not been considered in immunocompetent women. The aim of this study was to identify cytological atypia and human papillomavirus (HPV) DNA in intra-anal specimens from human immunodeficiency virus (HIV)-negative women with and without genital HPV lesions. This study was a cross-sectional analysis of 142 women who were negative for the HIV: 80 with genital lesions that were associated with HPV and 62 without HPV-induced lesions. The women were evaluated at the Federal University of Ceará from October 2011 to June 2012. The statistical analysis included the Fisher exact test and the odds ratio (CI 95%). Atypical anal cytology was observed in 24 (29.3%) patients in the study group and in 11 (17.8%) patients in the control group. In cases with at least two sites of HPV-associated lesions, 12 (41.4%) presented atypical cytology (P = 0.0220; OR = 2.7621, 1.1579-6.5889). When the practice of anal sex was evaluated, atypical cytology was observed in 22/43 (34%) [P = 0.0214; OR = 2.519, 1.146-5.534]. HPV DNA was detected in 17/27 (63%) cases with at least two sites of lesions (P = 0.0293, OR = 2.4855, 1.0960-5.6367). In the 33 cases who presented positive HPV DNA test results, the liquid-based cytology results were atypical (P = 0.0212, OR = 2.8, 1.1665-6.7208). Based on the results, liquid-based cytology may be used to detect intra-anal lesions, especially among women who have a history of anal intercourse or who have genital HPV-associated lesions at multiple sites.

Combined P16 and human papillomavirus testing predicts head and neck cancer survival

While its prognostic significance remains unclear, p16(INK4a) protein expression is increasingly being used as a surrogate marker for oncogenic human papillomavirus (HPV) infection in head and neck squamous cell carcinomas (HNSCC). To evaluate the prognostic utility of p16 expression in HNSCC, we prospectively collected 163 primary tumor specimens from histologically confirmed HNSCC patients who were followed for up to 9.4 years. Formalin fixed tumor specimens were tested for p16 protein expression by immunohistochemistry (IHC). HPV type-16 DNA and RNA was detected by MY09/11-PCR and E6/E7 RT-PCR on matched frozen tissue, respectively. P16 protein expression was detected more often in oropharyngeal tumors (53%) as compared with laryngeal (24%), hypopharyngeal (8%) or oral cavity tumors (4%; p<0.0001). With respect to prognosis, p16-positive oropharyngeal tumors exhibited significantly better overall survival than p16-negative tumors (log-rank test p=0.04), whereas no survival benefit was observed for nonoropharyngeal tumors. However, when both p16 and HPV DNA test results were considered, concordantly positive nonoropharyngeal tumors had significantly better disease-specific survival than concordantly negative nonoropharyngeal tumors after controlling for sex, nodal stage, tumor size, tumor subsite, primary tumor site number, smoking and drinking [adjusted hazard ratio (HR)=0.04, 0.01-0.54]. Compared with concordantly negative nonoropharyngeal HNSCC, p16(+)/HPV16(-) nonoropharyngeal HNSCC (n=13, 7%) demonstrated no significant improvement in disease-specific survival when HPV16 was detected by RNA (adjusted HR=0.83, 0.22-3.17). Our findings show that p16 IHC alone has potential as a prognostic test for oropharyngeal cancer survival, but combined p16/HPV testing is necessary to identify HPV-associated nonoropharyngeal HNSCC with better prognosis.

Human Papillomavirus–Unrelated Gastric Type of Cervical Adenocarcinoma Presenting With a Metastatic Ovarian Tumor

Gastric type of adenocarcinoma (GAC) is a newly reported, morphologically distinct, mucinous subtype of cervical adenocarcinoma and is distinguished by aggressiveness and fatal outcomes. The association between human papillomavirus (HPV) and cervical carcinoma is well known; however, GAC is almost always HPV negative. We report an unusual case of cervical GAC in a 41-year-old woman with a metastatic ovarian mass. The histological morphology of both tumors consisted of irregular glands lined by mucous cells with mild to moderate nuclear atypia and containing abundant cytoplasmic mucin. Immunohistochemical studies of the tumor cells revealed positive reactivity for CK7 and carcinoembryonic antigen but negative reactivity for p16 and HPV DNA usually expressed in cervical adenocarcinoma. Further staining for mucin with monoclonal antibody HIK1083 showed positive reactivity in both cervical and ovarian tumors. A gastric type of cervical carcinoma is considered. The patient is free of detectable disease at a 12-month follow-up. P16 staining and HPV DNA test result are usually positive in usual mucinous type of cervical adenocarcinoma, but they are negative in GAC. HIK1083 is becoming more commonly used for the diagnosis of GAC. Differentiation of GAC from usual mucinous type of cervical adenocarcinoma is important because GAC was related to a significant risk of recurrence and decreased 5-year disease-specific survival. We suggest applying HIK1083 in the diagnosis of cervical adenocarcinoma, especially in a small biopsy specimen.

Cytology and Human Papillomavirus Testing 6 to 12 Months after ASCUS or LSIL Cytology in Organized Screening To Predict High-Grade Cervical Neoplasia between Screening Rounds

We carried out a prospective study comparing the performance of human papillomavirus (HPV) E6/E7 mRNA (PreTect HPV-Proofer; NorChip, Klokkarstua, Norway) and DNA (Amplicor HPV test; Roche Diagnostics, Basel, Switzerland) triage testing of women 6 to 12 months after atypical-squamous-cells-of-undetermined-significance (ASCUS) or low-grade-squamous-intraepithelial-lesion (LSIL) cytology in organized screening to predict high-grade cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) between screening rounds. Between January 2005 and April 2008, 692 study women with screening-detected ASCUS/LSIL cytology 6 to 12 months earlier returned for HPV mRNA and DNA testing and repeat cytology. The median follow-up time was 3 years, using existing health care facilities. Follow-up test results were available for 625 women. Of the 145 CIN2+ cases detected during the study period, 95 (65.5%) were HPV mRNA positive 6 to 12 months after screening-detected ASCUS/LSIL, 44 (30.4%) were HPV mRNA negative, and 6 (4.1%) were invalid. The corresponding HPV DNA results were 139 (95.9%), 5 (3.4%), and 1 (0.7%), respectively. The cumulative incidences of CIN2+ 3 years after a negative HPV mRNA and DNA test were 10.3% (95% confidence interval [CI], 7.2 to 13.3%) and 1.8% (95% CI, 0.0 to 3.6%), respectively. The cumulative incidences of CIN2+ 3 years after positive HPV mRNA and DNA tests were 52.8% (95% CI, 40.1 to 60.1%) and 41.3% (95% CI, 35.5 to 46.6%), respectively. In conclusion, both positive HPV mRNA and DNA test results have a high enough long-term prediction of CIN2+ risk to consider referral to colposcopy as good practice when performed in delayed triage of women with ASCUS/LSIL cytology. In addition, the low CIN2+ risk among women with a negative Amplicor HPV test in our study confirms its safe use in a clinical setting.

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.

Brief Research Report: Uncertainty-Inducing and Reassuring Facts About HPV: A Descriptive Study of French Canadian Women

We sought to describe information that makes women feel (1) uncertain and (2) reassured about their human papillomavirus (HPV) status and the potential health implications of an HPV DNA test result and (3) to examine information seeking after receiving their result. Thirty women (previously tested HPV negative) read factual information on HPV and cervical cancer and were asked which facts were uncertainty inducing and which were reassuring. Twenty-four facts reassured women of their HPV negative status, 11 facts made women feel uncertain, and 10 facts made them feel both. The most common reason for seeking information in the future was receiving a positive test result. The authors outline what specific facts about HPV health providers can emphasize to alleviate anxiety and encourage women to feel reassured of their low cancer risk following a negative test result.

High-Risk Human Papillomavirus DNA Test Results Are Useful for Disease Risk Stratification in Women With Unsatisfactory Liquid-Based Cytology Pap Test Results

This study assesses whether high-risk human papillomavirus (HPV) DNA test results from residual vial fluid of unsatisfactory liquid-based cytology(LBC) samples might provide useful information on disease risk. Patients with unsatisfactory imaged ThinPrep Pap test results and available Hybrid Capture 2 high-risk HPV results were identified at an academic women's hospital laboratory between July 1, 2005, and July 31, 2007. Follow-up repeat cytology results, HPV results, and available biopsy results were analyzed. Three hundred four patients with unsatisfactory cytology results and HPV test results were studied. Eleven (3.6%) of 304 tested positive for HPV DNA, and 293 tested HPV negative. Five (45%) of 11 HPV-positive patients had detectible low-grade squamous intraepithelial/cervical intraepithelial neoplasia 1 during a mean follow-up period of almost 6 months. Among 293 women with negative HPV results, only 1 case of cervical intraepithelial neoplasia 1 was identified during roughly the same follow-up period. A positive high-risk HPV result associated with an unsatisfactory ThinPrep Pap test result identified patients at risk for diagnosis of an undetected squamous intraepithelial/cervical intraepithelial neoplasia. Negative high-risk HPV results associated with an unsatisfactory LBC had high negative predictive value in this limited study. The overall low detection rate for significant disease on follow-up of all patients with unsatisfactory imaged LBC is similar to findings reported in another LBC study but differs from studies reporting increased risk for undetected disease in women screened with unsatisfactory conventional Pap smears.

The utility of the human papillomavirus DNA load for the diagnosis and prediction of persistent vaginal intraepithelial neoplasia

We evaluated the human papillomavirus (HPV) DNA load for the diagnosis and prediction of persistent vaginal intraepithelial neoplasia (VAIN). A retrospective review of the medical records of patients with a pathological diagnosis of VAIN was performed. Eligible women (N=48) were followed for cytology and HPV DNA test, and colposcopic biopsies were taken at 3- to 6-month intervals. Thirty-seven patients were followed for more than 6 months; their HPV DNA test results were compared to the cytology results for the prediction of disease prognosis. The degree of VAIN was more severe in patients with a high initial HPV DNA load (p=0.009). Patients with VAIN 2 and VAIN 3 were older than those with VAIN 1 (p=0.005 and 0.008, respectively). In 26 out of 37 patients (70.3%), the VAIN resolved. The other patients had persistent lesions with no progression to invasive vaginal carcinoma. The last follow-up HPV DNA load was significantly higher in the group with persistent VAIN compared to the group with resolved VAIN (p<0.0001). Negative cytology was observed in 25 out of 26 patients in the VAIN resolved group and in nine out of 11 patients in the VAIN persistent group (p=0.205). These results suggest that the HPV DNA test, especially for viral load, was more effective for the diagnosis and prediction of persistent VAIN than cytology.

Detection of human papillomavirus infection in penile samples through liquid-based cytology and polymerase chain reaction

The human papillomavirus (HPV) is strongly related to cervical cancer and its precursor lesions. However, unlike in the case of women, there are limited data regarding HPV infection in men. Analysis of male HPV infection is frequently hindered by the lack of consistency in collection methods, sample adequacy, and low sensitivity of cytologic analysis. The objective of the current study was to compare the results of liquid-based cytology and HPV DNA testing through polymerase chain reaction in 99 penile samples collected from men presenting with condyloma acuminate or male partners of HPV-infected women who had attended a public health service in the city of Belo Horizonte, Minas Gerais, Brazil. Classic and nonclassic cytomorphologic signs were adopted to evaluate the presence of HPV infections in penile smears. HPV DNA was detected in 93 (93.9%) of the 99 samples analyzed. Koilocytosis was detected in 1 smear and nonclassic signs were detected in 23 smears, 22 of which were found to be positive for HPV DNA. The cytopathologic detection of HPV infection in penile samples collected for liquid-based cytology is low, even when cytologic nonclassic signs are applied, and does not appear to improve the diagnosis of HPV infection in men.

Interobserver Agreement in the Evaluation of Digitized Cervical Images

To estimate the agreement among multiple expert colposcopists evaluating high-resolution digitized cervigrams taken from patients with a variety of human papillomavirus (HPV) infection states and previous cervigram interpretations. Twenty expert colposcopists evaluated 939 digitized images of the uterine cervix obtained after the application of 5% acetic acid during the ASCUS-LSIL Triage Study. Twenty images selected to represent a broad range were graded by all the colposcopists. The remaining 919 pictures were distributed by stratified random sampling, such that each image was evaluated by two colposcopists, and each expert evaluated 112 images with similar distributions of cervigram diagnoses and HPV DNA test results. We evaluated interrater agreement among the pairs of colposcopists and confirmed the conclusions using the 20 images they all graded. Pairs of colposcopists agreed on the diagnosis for only 56.8% of images. Similar agreement was seen regarding number of visible lesions (of low-grade or greater). This variability in ratings remained when the images were stratified by final histologic diagnosis or HPV status. The results were confirmed by the presence of large variability in ratings (ranging in some cases from normal to cancer) for the 20 images graded by all colposcopists. Colposcopic diagnosis using static images is poorly reproducible and might reflect similar problems in clinical practice. Researchers should question the use of colposcopic images as a reference standard for teaching and evaluating the presence or severity of disease.

The Impact of HIV Status and Type on the Clearance of Human Papillomavirus Infection among Senegalese Women

Persistent infection with human papillomavirus (HPV) is associated with the development and progression of HPV-related disease, including cervical intraepithelial neoplasia (CIN) and invasive cervical cancer. We examined the impact of human immunodeficiency virus (HIV) status and type on the clearance of HPV infection among 614 Senegalese women enrolled in a longitudinal study of HPV and CIN. Women were examined every 4 months for HPV DNA. Clearance was defined as 2 consecutive negative HPV DNA test results. Cox proportional hazard regression with time-dependent covariates indicated that HIV-positive women were less likely to clear HPV infection (adjusted hazard ratio [HR], 0.31 [95% confidence interval {CI}, 0.21-0.45]) than HIV-negative women. Among HIV-positive women, those with CD4 cell counts <200 or from 200 to 500 cells/microL showed a 71% (adjusted HR, 0.29 [95% CI, 0.11-0.76]) and 32% (adjusted HR, 0.68 [95% CI, 0.31-1.48]) reduction in the likelihood of HPV clearance, respectively, compared with those with CD4 cell counts >500 cells/microL. HIV-2 infection was associated with an increased likelihood of HPV clearance (adjusted HR, 2.46 [95% CI, 1.17-5.16]), compared with that for HIV-1 infection. HIV infection reduces the likelihood of HPV clearance. Among HIV-positive women, immunosuppression, as measured by CD4 cell count, reduces the likelihood of HPV clearance, and HIV type appears to be associated with HPV clearance.

Cost-Effectiveness Analysis Based on the Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study (ALTS)

The ALTS (atypical squamous cells of undetermined significance [ASCUS] and low-grade squamous intraepithelial lesion [LSIL] Triage Study) suggests that, for women diagnosed with ASCUS, human papillomavirus (HPV) DNA testing followed by referral to colposcopy of only those women with oncogenic HPV (i.e., HPV DNA testing) is as effective at detecting cervical intraepithelial neoplasia (CIN) 3 or cancer (CIN3+) as referring all women with ASCUS for immediate colposcopy. We conducted a cost-effectiveness analysis of the ALTS trial to determine whether HPV DNA testing is a cost-effective alternative to immediate colposcopy or conservative management with up to three cytology examinations. Data from the ALTS trial were used in conjunction with medical care costs in a short-term decision model. The model compared the incremental costs per case of CIN3+ detected as measured by the incremental cost-effectiveness ratio (ICER) for the following management strategies for women with ASCUS: immediate colposcopy, HPV DNA testing, and conservative management with up to three cytology examinations. The least costly and least sensitive strategy was conservative management with one repeat cytology examination using a threshold of high-grade squamous intraepithelial lesion (HSIL) for referral to colposcopy. Compared with this strategy, triage to colposcopy based on a positive HPV DNA test result had an ICER of 3517 dollars per case of CIN3+ detected. Immediate colposcopy and conservative management with up to three repeat cytology visits detected fewer cases of CIN3+ and were more costly than HPV DNA testing. Immediate colposcopy became cost-effective at 20,370 dollars compared with HPV DNA testing only if colposcopy and biopsy were assumed to be 100% sensitive. HPV DNA testing is an economically viable strategy for triage of ASCUS cytology. The less than perfect sensitivity of colposcopy and biopsy needs to be accounted for in future clinical guidelines and policy analyses.