Recommendations for screening and early detection of common cancers in India.

Cancers of the breast, uterine cervix, and lip or oral cavity are three of the most common malignancies in India. Together, they account for about 34% of more than 1 million individuals diagnosed with cancer in India each year. At each of these cancer sites, tumours are detectable at early stages when they are most likely to be cured with standard treatment protocols. Recognising the key role that effective early detection and screening programmes could have in reducing the cancer burden, the Indian Institute for Cytology and Preventive Oncology, in collaboration with the US National Cancer Institute Center for Global Health, held a workshop to summarise feasible options and relevant evidence for screening and early detection of common cancers in India. The evidence-based recommendations provided in this Review are intended to act as a guide for policy makers, clinicians, and public health practitioners who are developing and implementing strategies in cancer control for the three most common cancers in India.

A case for immunization of human papillomavirus (HPV) 6/11-infected pregnant women with the quadrivalent HPV vaccine to prevent juvenile-onset laryngeal papilloma.

Juvenile-onset recurrent respiratory papillomatosis (JORRP) is a rare disease caused by intrapartum or perinatal transmission of human papillomavirus (HPV) types 6 and 11 from an infected mother to the newborn. Immunization of a pregnant woman who has condyloma or HPV-6/11 infection with the quadrivalent HPV vaccine will result in a high neutralizing antibody response to HPV 6 and HPV 11 in her serum, and these antibodies transferred to the newborn will likely protect the child against the development of JORRP. Because of the low incidence of disease in at-risk children, it may be difficult to test the effectiveness of maternal immunization for prevention of JORRP.

Acceptability of HPV vaccine implementation among parents in India.

Due to high cervical cancer rates and limited research on human papillomavirus (HPV) vaccine acceptability in India, the research team examined parental attitudes toward HPV vaccines. Thirty-six interviews with parents were conducted to assess sexually transmitted infection (STI)-related knowledge and HPV-specific vaccine awareness and acceptability. Despite limited knowledge, parents had positive views toward HPV vaccines. Common barriers included concerns about side effects, vaccine cost, and missing work to receive the vaccine. Parents were strongly influenced by health care providers' recommendations. Our findings suggest that addressing parental concerns, health worker training and polices, and efforts to minimize cost will be central to successful HPV vaccine implementation.

JC virus antibody and viremia as predictors of progressive multifocal leukoencephalopathy in human immunodeficiency virus-1-infected individuals.

We examined whether prediagnostic John Cunningham virus (JCV) antibodies and viremia are predictors of progressive multifocal leukoencephalopathy (PML) in 83 PML cases and 240 human immunodeficiency virus (HIV) disease-matched controls. JCV viremia was not predictive of PML, but some patients showed higher anti-JCV immunoglobulin G (IgG) responses 6 months prior to diagnosis.

Looking ahead: a case for human papillomavirus testing of self-sampled vaginal specimens as a cervical cancer screening strategy.

Even in the era of highly effective human papillomavirus (HPV) prophylactic vaccines, substantial reduction in worldwide cervical cancer mortality will only be realized if effective early detection and treatment of the millions of women already infected and the millions who may not receive vaccination in the next decade can be broadly implemented through sustainable cervical cancer screening programs. Effective programs must meet three targets: (i) at least 70% of the targeted population should be screened at least once in a lifetime, (ii) screening assays and diagnostic tests must be reproducible and sufficiently sensitive and specific for the detection of high-grade precursor lesions (i.e., CIN21), and (iii) effective treatment must be provided. We review the evidence that HPV DNA screening from swabs collected by the women in their home or village is sufficiently sound for consideration as a primary screening strategy in the developing world, with sensitivity and specificity for detection of CIN21 as good or better than Pap smear cytology and VIA. A key feature of a self-collected HPV testing strategy (SC-HPV) is the move of the primary screening activities from the clinic to the community. Efforts to increase the affordability and availability of HPV DNA tests, community education and awareness, development of strong partnerships between community advocacy groups, health care centers and regional or local laboratories, and resource appropriate strategies to identify and treat screen-positive women should now be prioritized to ensure successful public health translation of the technologic advancements in cervical cancer prevention.

Shedding of Epstein-Barr virus and cytomegalovirus from the genital tract of women in a periurban community in Andhra Pradesh, India.

We found a large number of false-positive readings by visual inspection with acetic acid (VIA) in a study of cervical cancer screening strategies (VIA, human papillomavirus HPV DNA testing, and Pap cytology) in a periurban community in Andhra Pradesh, India. We evaluated whether these false-positive readings might be occurring as a result of infections with Epstein-Barr virus (EBV) or cytomegalovirus (CMV), prevalent latent herpesviruses known to be shed from the female genital tract. While we found that there was no association between VIA results and the presence of EBV or CMV in the cervix, we did find a high prevalence of both viruses: 20% for EBV and 26% for CMV. In multivariate analyses, CMV prevalence was associated with younger age, lack of running water in the home, and visually apparent cervical inflammation. EBV prevalence was associated with older age and a diagnosis of cervical intraepithelial neoplasia grade 1 or greater. The biological and clinical implications of these viruses at the cervix remain to be determined. The strong association between the presence of EBV and cervical disease warrants future exploration to determine whether EBV plays a causal role in disease development or if it is merely a bystander in the process.

HPV testing for cervical cancer screening appears more cost-effective than Papanicolau cytology in Mexico.

OBJECTIVE: To determine the incremental costs and effects of different HPV testing strategies, when compared to Papanicolau cytology (Pap), for cervical cancer screening in Mexico. METHODS: A cost-effectiveness analysis (CEA) examined the specific costs and health outcomes associated with (1) no screening; (2) only the Pap test; (3) only self-administered HPV; (4) only clinician administered HPV; and (5) clinician administered HPV plus the Pap test. The costs of self- and clinician-HPV testing, as well as with the Pap test, were identified and quantified. Costs were reported in 2008 US dollars. The health outcome associated with these screening strategies was defined as the number of high-grade cervical intraepithelial neoplasia or cervical cancer cases detected. This CEA was performed using the perspective of the Mexican Institute of Social Security (IMSS) in Morelos, Mexico. RESULTS: Screening women between the ages of 30-80 for cervical cancer using clinical-HPV testing or the combination of clinical-HPV testing, and the Pap is always more cost-effective than using the Pap test alone. CONCLUSIONS: This CEA indicates that HPV testing could be a cost-effective screening alternative for a large health delivery organization such as IMSS. These results may help policy-makers implement HPV testing as part of the IMSS cervical cancer screening program.

Bacterial vaginosis and the natural history of human papillomavirus.

OBJECTIVE: To evaluate associations between common vaginal infections and human papillomavirus (HPV). STUDY DESIGN: Data from up to 15 visits on 756 HIV-infected women and 380 high-risk HIV-uninfected women enrolled in the HIV Epidemiology Research Study (HERS) were evaluated for associations of bacterial vaginosis, trichomoniasis, and vaginal Candida colonization with prevalent HPV, incident HPV, and clearance of HPV in multivariate analysis. RESULTS: Bacterial vaginosis (BV) was associated with increased odds for prevalent (aOR = 1.14, 95% CI: 1.04, 1.26) and incident (aOR = 1.24, 95% CI: 1.04, 1.47) HPV and with delayed clearance of infection (aHR = 0.84, 95% CI: 0.72, 0.97). Whereas BV at the preceding or current visit was associated with incident HPV, in an alternate model for the outcome of incident BV, HPV at the current, but not preceding, visit was associated with incident BV. CONCLUSION: These findings underscore the importance of prevention and successful treatment of bacterial vaginosis.

Suitability of self-collected vaginal samples for cervical cancer screening in periurban villages in Andhra Pradesh, India.

OBJECTIVES: Our aim was to determine if (1) Hybrid Capture 2 and a PCR-based method were comparable for detection of high-risk human papillomavirus (HPV) clinician-collected and self-collected samples were equally efficient to detect HPV and cervical cancer precursor lesions, and (3) if participation rates improved with home-based versus clinic-based self collection. METHODS: Samples were selected from women participating in a cervical cancer screening study according to HPV, visual inspection with acetic acid, or Pap smear screening results. From 432 of 892 selected women, split sample aliquots were tested for HPV DNA using both the Hybrid Capture 2 assay and the Roche prototype line blot assay. Women from a subset of villages were recruited at two separate time points for clinic-based self-collection and home-based self-collection, and participation rates were compared. RESULTS: Pairwise agreement between self- and clinician-collected samples was high by both Hybrid Capture 2 (90.8% agreement, kappa = 0.7) and PCR (92.6% agreement, kappa = 0.8), with significantly increased high-risk HPV detection in clinician-collected specimens (McNemar's P < 0.01). Ability to detect precursor lesions was highest by PCR testing of clinician-collected samples and lowest by Hybrid Capture 2 testing of self-collected samples (11 of 11 and 9 of 11 cases of cervical intraepithelial neoplasia grade 2/3 and cancer detected, respectively). Participation in home-based screening was significantly higher than clinic-based screening (71.5% and 53.8%, respectively; P < 0.001) among women ages 30 to 45 years. CONCLUSION: The combination of improved screening coverage and a high single test sensitivity afforded by HPV DNA testing of home-based self-collected swabs may have a greater programmatic effect on cervical cancer mortality reduction compared with programs requiring a pelvic exam.

Investigation of pre-diagnostic virological markers for progressive multifocal leukoencephalopathy in human immunodeficiency virus-infected patients.

Progressive multifocal leukoencephalopathy (PML) is a severe neurological disorder due to JC virus (JCV) infection. Pre-diagnostic biological markers and risk factors for PML are not well understood. We conducted a case-control study nested within the Multicenter AIDS Cohort Study to examine the association between JCV viruria and viremia and serum antibody to JCV capsids, in relation to subsequent PML diagnoses, 5 months to 12 years later. Other demographic and immunologic factors were also examined. The study population included 28 incident cases of PML, 26 matched HIV-positive controls, and 50 HIV-negative controls. Prevalence of JCV viruria was 37% in cases, 42% in HIV-positive controls, and 28% in HIV-negative controls (P = 0.43). Among persons with JCV viruria, persistent viruria was more common in cases (89%) than in HIV-positive controls (33%) (P = 0.02). Presence of JCV viruria was not related to the time to PML diagnosis (OR: 1.03, 95% CI: 0.8-1.4); however, the urinary concentration of JCV DNA increased with proximity to the date of PML diagnosis in cases. JCV seropositivity did not differ between cases or controls (P = 0.42). Four cases tested JCV seronegative, including one case only 5 months prior to diagnosis with PML. JCV DNA was detected in the serum of one HIV-positive control. Smoking was the only demographic variable analyzed associated with an increased risk for PML (MOR: 9.0, 95% CI: 1.2-394.5). The results suggest that persistent JCV viruria and increasing urinary concentration of JCV DNA may be predictive of PML for some patients.

Determinants of newly detected human papillomavirus infection in HIV-infected and HIV-uninfected injection drug using women.

BACKGROUND: We sought to identify factors associated with newly detected human papillomavirus (HPV) infection in a high-risk cohort of injection drug using women in Baltimore, MD. METHODS: We studied 146 HIV-infected and 73 HIV-uninfected female participants in a 5-year prospective HIV natural history study. We examined the association of sexual and nonsexual risk factors and newly detected type-specific HPV infection as determined by consensus PCR between consecutive visits. RESULTS: Newly detected HPV was more common among HIV-infected versus HIV-uninfected women (30% and 6%, respectively; P <0.01). Among the entire cohort, recent crack use (OR, 1.7; 95% CI, 1.1-2.6) and HIV infection/CD4 cell count were independent predictors for new HPV detection (HIV-uninfected as reference, OR, 4.6; 95% CI, 2.3-8.9, OR, 5.4; 95% CI, 2.8-10.3, and OR, 10.9; 95% CI, 5.5-21.7 for HIV-infected CD4 >500, 200-500, and <200, respectively). Among HIV-uninfected women, recent marijuana use was an independent predictor of newly detected HPV infection (OR, 3.5; 95% CI, 1.3-9.5). CONCLUSIONS: Newly detected HPV clearly increased with greater immunosuppression in HIV-infected injection drug users. Larger studies of HIV-uninfected and infected high-risk individuals are needed to clarify the independent associations of crack and marijuana use with new (or reactivated) HPV infection.

The effect of highly active antiretroviral therapy on human papillomavirus clearance and cervical cytology.

OBJECTIVE: To examine the association of highly active antiretroviral therapy (HAART) with human papillomavirus (HPV) clearance and progression or regression of cervical cytological abnormalities in women with human immunodeficiency virus (HIV). METHODS: Five hundred thirty-seven women with HIV participating in the HIV Epidemiology Research Study, an observational, multisite cohort study, were evaluated semiannually from 1996 to 2000. Cervical Pap tests were collected for cervical cytology. Testing for HPV was conducted by polymerase chain reaction. Cox proportional hazard models were used to calculate hazard ratios and 95% confidence intervals (CIs). Number needed to treat (NNT) at 2 years was calculated for HAART. RESULTS: Among women with cervical squamous intraepithelial lesions, HAART was associated with an increased likelihood of HPV clearance (hazard ratio 4.5, 95% CI 1.2-16.3, NNT 22.4). Use of HAART was not associated with an increased likelihood of HPV clearance among women with normal cervical cytology (hazard ratio 1.7, 95% CI 0.9-3.1, NNT 6.5) or atypical squamous cells of undetermined significance cytology (hazard ratio 1.0, 95% CI 0.4-2.5, NNT 174.0). Use of HAART was not significantly associated with an increased likelihood of cervical cytologic regression (hazard ratio 1.3, 95% CI 1.0-1.7, NNT 10.9) or cervical cytologic progression (hazard ratio 0.7, 95% CI 0.6-1.0, NNT 12.8). CONCLUSION: Among women with preexisting abnormal cervical cytology, HAART was associated with enhanced HPV clearance but not with Pap test regression. Close monitoring of women with HIV for cervical cytologic abnormalities, regardless of HAART treatment status, is warranted. LEVEL OF EVIDENCE: II.

Determinants of incidence and clearance of high-risk human papillomavirus infections in rural Rakai, Uganda.

BACKGROUND: We used self-administered vaginal swabs to assess the incidence and clearance of carcinogenic human papillomavirus (HPV) infections in rural Rakai, Uganda. METHODS: Women provided self-administered vaginal swab at annual home-based visits. Type-specific carcinogenic HPV incidence and clearance and risk factors were assessed. RESULTS: Carcinogenic HPV incidence was 17.3 per 100 person-years among HIV-positive women compared with 7.0 per 100 person-years among HIV-negative women (P < 0.001). HPV-51 had the highest incidence followed by HPV-16 (1.8 per 100 and 1.5 per 100 person-years, respectively). In multivariate model, HIV-positive women were twice as likely to have incident infection compared with HIV-negative women. Younger women were at higher risk for incident infection, as were women with higher lifetime and recent sexual partners, and high perception of AIDS. Married women were less likely to have incident infection. Approximately half of all carcinogenic HPV infections cleared over the study follow-up of 3 years. HPV-31, HPV-35, and HPV-16 had the lowest clearance (16.7%, 27.9%, and 38.3%, respectively). In multivariate model, HIV-positive, women over 30 years with higher HPV viral, burden and more lifetime sex partners were less likely to clear infections. CONCLUSIONS: Self-collected vaginal swabs provide accurate HPV exposure assessment for studying HPV exposure and epidemiology and can be an important tool for research in populations unwilling to undergo pelvic exam.

Human papillomavirus-type distribution in women with and without cervical neoplasia in north India.

Our objective was to determine the human papillomavirus (HPV)-type prevalence in cervical samples in women with and without cervical neoplasia in an opportunistic hospital-based cancer-screening program. A cross-sectional study of 524 women presenting from January 2003 through June 2005 with symptoms of persistent vaginal discharge, intermenstrual bleeding, and postcoital bleeding or detected to have an unhealthy cervix underwent HPV genotyping by consensus polymerase chain reaction and reverse line-blot hybridization assay, conventional Pap smear, and colposcopy, with directed biopsy from all lesions detected. The prevalence rates of HPV infection among women with normal, low-grade cervical neoplasia (CIN 1) and high-grade CIN (>CIN2) were found to be 7.6%, 42.3%, and 87.5%, respectively. Seventeen high-risk and 6 low-risk HPV types were identified by the reverse line-blot assay. Multiple infections were seen in 20% of women. In normal women, the 6 commonest types were HPV-16, HPV-89, HPV-39, HPV-52, HPV-62, and HPV-18, whereas in high-grade disease, these were all high-risk types HPV-16, HPV-18, HPV-33, HPV-39, HPV-35, and HPV-56. HPV-16 was the commonest type in all groups, seen in 49.4% cases overall and in 74.3% of high-grade squamous intraepithelial lesion. It was followed by HPV-18 (7.4%) and HPV-33 and HPV-39 (4.9% each). HPV-89 was the commonest low-risk type (9.9%). HPV-16/18 were associated with 34.3% of normal, 45.4% of low-grade and 65.7% of high-grade lesions. A wide spectrum of HPV types is seen in north Indian women, with the majority being HPV-16 in all grades of histology. A vaccine against HPV-16 and HPV-18 could prevent two thirds of cases of high-grade cervical neoplasia.

Epidemiologic classification of human papillomavirus types associated with cervical cancer.

BACKGROUND: Infection with human papilloma virus (HPV) is the main cause of cervical cancer, but the risk associated with the various HPV types has not been adequately assessed. METHODS: We pooled data from 11 case-control studies from nine countries involving 1918 women with histologically confirmed squamous-cell cervical cancer and 1928 control women. A common protocol and questionnaire were used. Information on risk factors was obtained by personal interviews, and cervical cells were collected for detection of HPV DNA and typing in a central laboratory by polymerase-chain-reaction-based assays (with MY09/MY11 and GP5+/6+ primers). RESULTS: HPV DNA was detected in 1739 of the 1918 patients with cervical cancer (90.7 percent) and in 259 of the 1928 control women (13.4 percent). With the GP5+/6+ primer, HPV DNA was detected in 96.6 percent of the patients and 15.6 percent of the controls. The most common HPV types in patients, in descending order of frequency, were types 16, 18, 45, 31, 33, 52, 58, and 35. Among control women, types 16, 18, 45, 31, 6, 58, 35, and 33 were the most common. For studies using the GP5+/6+ primer, the pooled odds ratio for cervical cancer associated with the presence of any HPV was 158.2 (95 percent confidence interval, 113.4 to 220.6). The odds ratios were over 45 for the most common and least common HPV types. Fifteen HPV types were classified as high-risk types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82); 3 were classified as probable high-risk types (26, 53, and 66); and 12 were classified as low-risk types (6, 11, 40, 42, 43, 44, 54, 61, 70, 72, 81, and CP6108). There was good agreement between our epidemiologic classification and the classification based on phylogenetic grouping. CONCLUSIONS: In addition to HPV types 16 and 18, types 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82 should be considered carcinogenic, or high-risk, types, and types 26, 53, and 66 should be considered probably carcinogenic.

Male circumcision, penile human papillomavirus infection, and cervical cancer in female partners.

BACKGROUND: It is uncertain whether male circumcision reduces the risks of penile human papillomavirus (HPV) infection in the man and of cervical cancer in his female partner. METHODS: We pooled data on 1913 couples enrolled in one of seven case-control studies of cervical carcinoma in situ and cervical cancer in five countries. Circumcision status was self-reported, and the accuracy of the data was confirmed by physical examination at three study sites. The presence or absence of penile HPV DNA was assessed by a polymerase-chain-reaction assay in 1520 men and yielded a valid result in the case of 1139 men (74.9 percent). RESULTS: Penile HPV was detected in 166 of the 847 uncircumcised men (19.6 percent) and in 16 of the 292 circumcised men (5.5 percent). After adjustment for age at first intercourse, lifetime number of sexual partners, and other potential confounders, circumcised men were less likely than uncircumcised men to have HPV infection (odds ratio, 0.37; 95 percent confidence interval, 0.16 to 0.85). Monogamous women whose male partners had six or more sexual partners and were circumcised had a lower risk of cervical cancer than women whose partners were uncircumcised (adjusted odds ratio, 0.42; 95 percent confidence interval, 0.23 to 0.79). Results were similar in the subgroup of men in whom circumcision was confirmed by medical examination. CONCLUSIONS: Male circumcision is associated with a reduced risk of penile HPV infection and, in the case of men with a history of multiple sexual partners, a reduced risk of cervical cancer in their current female partners.

Accuracy of Papanicolaou test among HIV-infected women.

OBJECTIVE: We examined the accuracy of the Papanicolaou (Pap) test among women with and women at high risk for human immunodeficiency virus (HIV) infection. METHODS: Pap test results and colposcopy findings were compared for 189 HIV-infected women and 95 HIV-uninfected women from the Baltimore HIV Epidemiology Research (HER) study site who were followed up semiannually from 1993 through 1999. Correlations were examined using data from individual visits that were analyzed using generalized estimating equation methods. RESULTS: Among women with normal results of Pap tests who underwent biopsy, the likelihood of cervical intraepithelial neoplasia was significantly greater for HIV-infected women (14.3%) than for HIV-uninfected women (1.2%) (P < .01). The specificity and negative predictive value of Pap testing were higher among HIV-uninfected women, regardless of whether detection of atypical squamous cells of undetermined significance was considered to be abnormal. Independent predictors of discordant cytologic and histologic findings included detection of human papillomavirus (adjusted odds ratio [OR], 3.1; 95% confidence interval [CI], 1.0-9.8) and a CD4 cell count of < 500 cells/microL (adjusted OR, 6.5; 95% CI, 1.5-29.2). Of the 19 HIV-infected women with normal cytologic findings and cervical intraepithelial neoplasia, 18 had abnormal Pap test findings (most often atypical squamous cells of undetermined significance) within 1 year of discordant cytologic and histologic findings. CONCLUSION: In this well-described cohort of women with and women at high risk for HIV infection, agreement between cytologic findings and colposcopic and histologic findings was high. A small number of HIV-infected women had cervical intraepithelial neoplasia, despite having normal cytologic findings; 95% of these women would have had cytologic abnormalities detected within 1 year of the discordant results by use of current guidelines for Pap test screening. These data fail to support the need for routine colposcopy in all HIV-infected women.

Prediagnostic circulating antibodies to JC and BK human polyomaviruses and risk of non-Hodgkin lymphoma.

Viral infections have been associated with increased risk of non-Hodgkin's lymphoma (NHL). We conducted a nested case-control study to investigate the association between prediagnostic serum antibodies to the human polyomaviruses, JC (JCV) and BK (BKV), and subsequent risk of NHL. Two research serum banks were established in Washington County, Maryland, in 1974 and 1989, with the collection of blood samples from >45,000 volunteers. Incident NHL cases diagnosed through 2002 (n = 170) were identified among participants by linkage to population-based cancer registries. Two controls were matched to each case (n = 340) on age, sex, and blood draw date. Prediagnostic IgG antibodies to JCV and BKV were measured using virus-like particle ELISA. Associations between JCV and BKV antibody seropositivity and NHL were estimated using conditional logistic regression. Overall, neither antibodies to JCV [odds ratio (OR), 0.83; 95% confidence interval (95% CI), 0.56-1.23] nor BKV (OR, 0.98; 95% CI, 0.64-1.48) were associated with an increased risk of NHL. Results were similar after stratification by NHL subtype or induction period and adjustment for EBV seropositivity. Among those who donated blood in both 1974 and 1989, an increase in JCV antibody levels over time was associated with a 4-fold increased risk of NHL compared with a steep decline in antibody levels (OR, 4.59; 95% CI, 1.30-16.25; P(trend) = 0.02). Whereas JCV seropositivity was not associated with NHL overall, the finding of an increased risk of NHL associated with increasing antibody levels among those who were seropositive at baseline warrants further research into factors influencing reactivation of JCV infection.

Spontaneous regression of high-grade cervical dysplasia: effects of human papillomavirus type and HLA phenotype.

PURPOSE: Persistent infection with oncogenic human papillomaviruses (HPV) plays a central etiologic role in the development of squamous carcinomas of the cervix and their precursor lesions, cervical intraepithelial neoplasias (CIN). We carried out a prospective observational cohort study evaluating known, quantifiable prognostic variables of clinical behavior in women with high-grade cervical lesions. EXPERIMENTAL DESIGN: Our study cohort included healthy women with high-grade cervical lesions (CIN2/3) with residual visible lesions after colposcopically directed biopsy. We prospectively followed 100 women over 15 weeks before standard resection. HPV typing was done using PCR and a reverse line blot detection method. RESULTS: The rate of spontaneous histologic regression, defined as (CIN1 or less at resection) was 28%. The overall rate of HPV infection was 100%. HPV16 was identified in 68% of the lesions. Women with HPV16 only were significantly less likely to regress, compared with women with HPV types other than HPV16 (odds ratio, 0.342; 95% confidence interval, 0.117-0.997; P = 0.049). In the cohort with HPV16 only, patients who had an HLA*A201 allele had similar outcomes to those who did not carry A201. However, among patients with HPV types other than HPV16, the HLA*A201 allele interaction was significant; patients with HLA*A201 were the least likely to resolve. CONCLUSIONS: CIN2/3 lesions associated with HPV16 alone are significantly less likely to resolve spontaneously than those caused by other types. Interactions among HPV type, HLA type, and regression rate support a role for HLA-restricted HPV-specific immune responses in determining disease outcome.

Polyomaviruses and human diseases.

Polyomaviruses are small, nonenveloped DNA viruses, which are widespread in nature. In immunocompetent hosts, the viruses remain latent after primary infection. With few exceptions, illnesses associated with these viruses occur in times of immune compromise, especially in conditions that bring about T cell deficiency. The human polyomaviruses BKV and JCV are known to cause, respectively, hemorrhagic cystitis in recipients of bone marrow transplantation and progressive multifocal leukoencephalopathy in immunocompromised patients, for example, by HIV infection. Recently, transplant nephropathy due to BKV infection has been increasingly recognized as the cause for renal allograft failure. Quantitation of polyomavirus DNA in the blood, cerebrospinal fluid, and urine, identification of virus laden "decoy cells" in urine, and histopathologic demonstration of viral inclusions in the brain parenchyma and renal tubules are the applicable diagnostic methods. Genomic sequences of polyomaviruses have been reported to be associated with various neoplastic disorders and autoimmune conditions. While various antiviral agents have been tried to treat polyomavirus-related illnesses, current management aims at the modification and/or improvement in the hosts' immune status. In this chapter, we provide an overview of polyomaviruses and briefly introduce its association with human diseases, which will be covered extensively in other chapters by experts in the field.