Unique variants of human papillomavirus genotypes 52 and 58 and risk of cervical neoplasia

Human papillomavirus (HPV) 52 and 58 are oncogenic HPV types prevalent in Asia. Our study aims to explore intratypic variants of HPV 52 and 58 in Taiwan. A total of 11,923 women were enrolled from seven townships in 1991–1992. HPV DNA in their cervical cells was detected and typed by EasyChip® HPV blot. Among 424 participants infected with HPV 52 and/or 58, nucleotide variations were determined in cervical cell samples of 406 participants by the polymerase chain reaction sequencing of the long control region, E6 and E7 genes. Nonprototype‐like variants including lineages B and C were detected in 278 (99.3%) of 280 HPV 52 samples. The prototype and prototype‐like group (lineage A) of HPV58 was found in 132 (98.5%) of 134 HPV 58 samples, with sublineage A1, A2 and A3 variant in 14.2, 27.6 and 56.7%, respectively. Among women infected with single HPV 52 type, the C variant (vs. B variant) was associated with an increased prevalence of cytologically diagnosed high‐grade squamous intraepithelial lesion or worse lesions showing an age‐adjusted odds ratio (95% confidence interval, CI) of 5.2 (1.0–27.6) and an increased prevalence of histologically confirmed high‐grade cervical intraepithelial neoplasia or more severe lesions with an age‐adjusted odds ratio (95% CI) of 7.6 (1.3–43.8). It was concluded that frequency distributions of HPV 52 and 58 variants in Taiwan were different from those in European and American populations. The association between C variant of HPV 52 and prevalence of cervical neoplasia needs further validation.     

Risk for high-grade cervical intraepithelial neoplasia associated with variants of human papillomavirus types 16 and 18.

BACKGROUND: Although the variant lineages of human papillomavirus (HPV) types 16 and 18 are well established, their individual associations with high-grade cervical intraepithelial neoplasia (CIN) have not been extensively evaluated. METHODS: Study subjects were women participating in the Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study who were positive for HPV16 or HPV18 at enrollment. These women were followed every 6 months for 2 years. Viral isolates from enrollment samples were characterized by DNA sequencing and classified as variant lineages. RESULTS: Over a 2-year study period, CIN3 was histologically diagnosed in 291 of the 779 HPV16-positive women and 47 of the 275 HPV18-positive women. Among women without CIN2-3 at enrollment, the risk of subsequent CIN3 was 2.7-fold greater for those with HPV16 African-2 [95% confidence interval (95% CI), 1.0-7.0] and 3.1-fold greater for those with HPV16 Asian American (95% CI, 1.6-6.0), compared with European variants. Relative to infection with HPV18 African variants, the risk associating subsequent CIN3 was 3.8 (95% CI, 0.9-17.2) for infection with HPV18 European variants and 4.8 (95% CI, 1.0-23.6) for infection with HPV18 Asian American variants. Similar associations were observed when the 2-year prevalence of CIN3 was used as the end point. Further, for those with HPV16 European variants, the 2-year prevalence of CIN3 was higher in White women than in African American women (P = 0.01); this trend was reversed for those with HPV16 African-1 variants (P = 0.22). A similar pattern was present for infections with HPV18 European versus African variants. CONCLUSIONS: The lineages of HPV16 and HPV18 variants are associated with differing risks for high-grade CIN.     

Cervical cytokines and clearance of incident human papillomavirus infection: Hawaii HPV cohort study

Mechanisms for the control and resolution of human papillomavirus (HPV) infection of the cervix include the local production of cytokines, which control recruitment and function of cells integral to pathogen control. We established a cohort of women for long‐term follow‐up to examine the mucosal expression of antiviral (IFN‐α2), Type‐1 (IFN‐γ, IL‐12), regulatory (IL‐10), and proinflammatory (IL‐1α, IL‐1β, IL‐6, IL‐8, MIP‐1α, and TNF) cytokines in association with the clearance of incident cervical HPV infection. Interviews and specimens for HPV DNA analysis and cytokine protein measurement were obtained at baseline and at 4‐month intervals. A Cox proportional hazards model was used to study the relationship between clearance of 107 high‐risk and 111 low‐risk incident HPV infections and cytokine levels among 154 women. Positive changes from baseline levels of IL‐10, IL‐12, MIP‐1α, and TNF were associated with significantly longer times to type‐specific HPV clearance. Inverse trends in the hazard ratios associated with clearance of high‐risk HPV infections were monotonic and significant for IL‐12 (p_trend = 0.02) and TNF (p_trend = 0.02); the likelihood of high‐risk HPV clearance was reduced by 65% and 67%, respectively, among women in the highest as compared with the lowest quartile of change from baseline. Our results suggest that in women with a nontransient cervical HPV infection, proinflammatory, Type‐1, and regulatory cytokines are elevated, underscoring the long‐term commitment of local immune mediators to viral eradication.     

Association of HPV16 E6 variants with diagnostic severity in cervical cytology samples of 354 women in a US population

It has been suggested that DNA sequence variants of HPV16 contribute to differences in the behavior of individual cervical lesions. To address this question, we have analyzed the association of HPV16 variants with diagnostic severity in 354 HPV16‐positive Oklahoman women. HPV16 variant status was determined by PCR amplification and DNA sequencing of the E6 open reading frame. European sequences were identified in 86% of samples and 14% were non‐European. Of the 51 non‐European cases, 61% were Asian‐American, 23% African and 16% were Native American variants. European prototype and related variants were present in comparable numbers (43% each) but the relative proportion of each differed with diagnostic category. In general, the proportion of European variants and non‐European variants increased with diagnostic severity while the European prototype decreased. When adjusted for age and race (white, black or Hispanic), the increased risk for carcinoma/severe dysplasia for non‐European variants was statistically significant with an odds ratio of 3.8 (1.3–10.7). However, the analogous comparison for the European variants, although also showing increased association with carcinoma/severe dysplasia, did not reach statistical significance (OR = 1.6 (95% CI 0.7–3.6). Overall, HPV16 European sequences (both prototype and related variants), were predominant in Oklahoman women including those with cancers. This suggests that while there appear to be differences among the HPV16‐variant categories in risk for progression to invasive cancer, all variant categories are associated with the development of invasive cancer. © 2009 UICC     

Prospective follow‐up of 2,065 young unscreened women to study human papillomavirus incidence and clearance

Human papillomavirus (HPV) is a necessary factor in the development of cervical intraepithelial neoplasia and cervical cancer. However, HPV is also a very common sexually transmitted virus and many women clear their infection. To study HPV incidence and clearance, 2,065 women, aged 18–29 years, were followed for 12 months and were asked to provide a self‐collected cervico‐vaginal sample and fill‐out a questionnaire every 3 months. For HPV DNA detection, the SPF₁₀‐DEIA LiPA₂₅ system was used. Incidence rates of any‐type high‐risk HPV and low‐risk HPV were 17.0 per 1,000‐person months, and 14.3 per 1,000‐person months, respectively. HPV types 16, 52, 51 and 31 had the highest type‐specific incidence rates. HPV incidence was increased in singles, and women having a new relationship. A higher number of lifetime sex partners, and a higher frequency of sexual contacts in the past 3 months was associated with an increased HPV incidence. The overall clearance of the newly detected type‐specific high‐risk HPV infections and low‐risk HPV infections was 61.2% and 69.0%, respectively. Having a sexual relationship compared to being single, and a higher sexual age both positively influenced the clearance of any‐type high‐risk HPV. Among the women infected with HPV 16, the women who had a co‐infection had a lower proportion of clearance of HPV 16. In conclusion, in this young Dutch study population, HPV incidence rates are not related to age and comparable to other western countries. Clearance was only independently related to factors associated with sexual behavior, either past or current.     

Association of human papillomavirus type 31 variants with risk of cervical intraepithelial neoplasia grades 2-3

Although the lineages of human papillomavirus type 31 (HPV31) variants are recognized, their clinical relevance is unknown. The purpose of our study was to examine risk of cervical intraepithelial neoplasia Grades 2-3 (CIN2/3) by HPV31 variants. Study subjects were women who participated in the atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion Triage Study and who had HPV31 infections detected at one or more visits. They were followed semi-annually over 2 years for detection of HPV DNA and cervical lesion. HPV31 isolates were characterized by DNA sequencing and assigned into 1 of 3 variant lineages. CIN2/3 was histologically confirmed in 127 (27.0%) of the 470 HPV31-positive women, 83 diagnosed at the first HPV31-positive visit and 44 thereafter. The odds ratio for the association of 2-year cumulative risk of CIN2/3 was 1.7 (95% CI: 1.0-2.9) for infections with A variants and 2.2 (95% CI: 1.2-3.9) for infections with B variants as compared to those with C variants. Among women without CIN2/3 at the first HPV31-positive visit, the risk of subsequent CIN2/3 was 2.2-fold greater for those with A variants (95% CI: 1.0-4.8) and 2.0-fold greater for those with B variants (95% CI: 0.9-4.9) as compared to those with C variants. Similar associations were observed when CIN3 was used as the endpoint. The findings from our study help to tag HPV31 variants that differ in risk of CIN2/3 and to explain in part why some HPV31 infections regress spontaneously and others lead to disease progression.     

Distress,anxiety, depression,and emotional well‐being in African‐American men with prostate cancer

Objective: African‐American men have an incidence rate of prostate cancer 60% higher than Caucasian men. Over one‐quarter of men with prostate cancer experience significant distress, yet psychosocial research has rarely focused on African‐American men. This study presents novel data on emotional well‐being, distress, anxiety, and depression in African‐American men with prostate cancer. Methods: This archival research combined two databases (N=385 and N=367) comprised of 55 African‐American men with prostate cancer. Quality of life was assessed with the Functional Assessment of Cancer Therapy, distress was measured with the Distress Thermometer, and anxiety and depression were measured with the Hospital Anxiety and Depression Scale. African‐American and Caucasian men were matched on age, education, and stage of disease, and compared on emotional well‐being, distress, anxiety, and depression. Results: The mean age of the 55 African‐American was 63 years old. In non‐matched comparison, African‐American men had elevated levels of distress, anxiety, and depression similar to Caucasian men. African‐American men reported high levels of clinically significant distress (>31%) and anxiety (>23%). However, after matching the African‐American and Caucasian men, African‐American men reported higher mean scores on emotional well‐being (p<0.05) and a lower percentage of African‐American men displayed clinically significant depressive symptoms (p<0.05) compared with Caucasian men. Conclusions: After matching the sample, African‐American men seem to display a sense of resilience, demonstrating greater emotional well‐being and a lower incidence of clinically significant depressive symptoms, compared with Caucasian men. This is consistent with cross‐cultural research outside of prostate cancer. Continued research is needed to further elucidate the concept of resiliency in African‐American men with prostate cancer. Copyright © 2010 John Wiley & Sons, Ltd.     

Distribution of human papillomavirus types 16 and 18 variants in squamous cell carcinomas and adenocarcinomas of the cervix

The distributions of human papillomavirus (HPV) types detected in cervical adenocarcinomas and squamous cell tumors differ. However, whether the distributions of intratypic HPV variants seen in these two histological forms of cervical disease differ is unknown. Our objective was to compare the distribution of HPV intratypic variants observed in squamous cell carcinomas (SCC) and cervical tumors of glandular origin (e.g., adenocarcinomas; AC) for two HPV types commonly observed in cervical tumors, HPV16 and HPV18. Participants in a multicenter case-control study of AC and SCC conducted in the eastern United States were studied. A total of 85 HPV16 and/or HPV18 positive individuals (31 diagnosed with AC, 43 diagnosed with SCC, and 11 population controls) were included. For HPV16-positive individuals, both the noncoding long control region and the E6 open reading frame were sequenced, and classified into phylogenetic-based lineage groups (European, Asian-American, African1, and African2). For HPV18-positive individuals, the long control region region only was sequenced and classified into known intratypic lineages (European, Asian-Amerindian, and African). The distribution of these different intratypic lineages among AC cases, SCC cases, and population controls was compared using standard methods. Non-European HPV16 and/or HPV18 intratypic variants were observed in 42% of ACs compared with 16% of SCCs and 18% of population controls (P = 0.04). Intratypic variants from the Asian-American lineage of HPV16 accounted for the differences seen between histological groups. The differences observed between AC and SCC cases were strongest for HPV16, and persisted in analysis restricted to Caucasian women, suggesting that the effect cannot be explained by differences in the ethnic make-up of AC versus SCC cases. Cervical AC and SCC differ not only with respect to the distribution of HPV types detected but also with respect to intratypic variants observed. Non-European HPV16 and/or HPV18 variants are commonly seen in AC. A possible hormonal mechanism is suggested to explain the observed findings.     

Genetic variations in human papillomavirus and cervical cancer outcomes

Cervical cancer is driven by persistent infection of human papillomavirus (HPV), which is influenced by HPV type and intratypic variants, yet the impact of HPV type and intratypic variants on patient outcomes is far less understood. Here, we examined the association of cervical cancer stage and survival with HPV type, clade, lineage, and intratypic variants within the HPV E6 locus. Of 1,028 HPV-positive cases recruited through the CerGE study, 301 were in-situ and 727 were invasive cervical cancer (ICC), with an average post-diagnosis follow-up of 4.8 years. HPV sequencing was performed using tumor-isolated DNA to assign HPV type, HPV 16 lineage, clade, and intratypic variants within the HPV 16 E6 locus, of which nonsynonomous variants were functionally annotated by molecular modeling. HPV 18-related types were more prevalent in ICC compared to in-situ disease and associated with significantly worse recurrence-free survival (RFS) compared to HPV 16-related types. The HPV 16 Asian American lineage D3 and Asian lineage A4 associated more frequently with ICC than with in situ disease and women with an intratypic HPV 16 lineage B exhibited a trend toward worse RFS than those with A, C, or D lineages. Participants with intratypic E6 variants predicted to stabilize the E6–E6AP–p53 complex had worse RFS. Variants within the highly immunogenic HPV 16 E6 region (E14–I34) were enriched in ICC compared to in-situ lesions but were not associated with survival. Collectively, our results suggest that cervical cancer outcome is associated with HPV variants that affect virus-host interactions.     

Variant‐specific persistence of infections with human papillomavirus Types 31, 33, 45, 56 and 58 and risk of cervical intraepithelial neoplasia

In our previous study of the etiologic role of oncogenic human papillomavirus (HPV) types other than HPV16 and 18, we observed a significantly higher risk of cervical intraepithelial neoplasia Grades 2–3 (CIN2/3) associated with certain lineages of HPV types 31/33/45/56/58 [called high‐risk (HR) variants] compared with non‐HR variants. This study was to examine whether these intra‐type variants differ in persistence of the infection and persistence‐associated risk of CIN2/3. Study subjects were women who had any of HPV types 31/33/45/56/58 newly detected during a 2‐year follow‐up with 6‐month intervals. For each type, the first positive sample was used for variant characterization. The association of reverting‐to‐negativity with group of the variants and CIN2/3 with length of positivity was assessed using discrete Cox regression and logistic regression, respectively. Of the 598 newly detected, type‐specific HPV infections, 312 became undetectable during follow‐up. Infections with HR, compared with non‐HR, variants were marginally more likely to become negative [adjusted hazard ratio = 1.3; 95% confidence interval (CI), 0.9–1.8]. The adjusted odds ratio associating with the development of CIN2/3 was 3.0 (95% CI, 1.2–7.4) for persistent infections with HR variants for 6 months and 10.0 (95% CI, 3.8–38.0) for persistent infections with HR variants for 12–18 months as compared with the first positive detection of HR variants. Among women with non‐HR variants, there were no appreciable differences in risk of CIN2/3 by length of positivity. Findings suggest that the lineage‐associated risk of CIN2/3 was not mediated through a prolonged persistent infection, but oncogenic heterogeneity of the variants.     

Treatment adherence and outcome in women with inflammatory breast cancer

BACKGROUND:

The authors compared treatment adherence rates and outcome in Caucasian and African American patients with inflammatory breast cancer (IBC).

METHODS:

The records of 55 (25 Caucasian and 30 African American) IBC patients treated with curative intent from 1995 to 2009 were reviewed. All patients received neoadjuvant doxorubicin (Adriamycin) and/or taxane‐based chemotherapy, and mastectomy with or without radiotherapy. The median follow‐up period for Caucasian and African American patients was similar (39.5 months and 36.1 months, respectively).

RESULTS:

There was no difference between races in median age, tumor size, grade, and receptor status at diagnosis. The number of patients who completed neoadjuvant chemotherapy, surgery, and radiotherapy did not differ by race (84% of Caucasians vs 86.7% of African Americans) nor did the median length of time to complete trimodality treatment (263 [range, 207‐422] days for Caucasians vs 262 [range, 165‐371] days for African Americans). There was a trend toward slightly higher pathological complete response rates in Caucasian than African American women (20% in Caucasians vs 6.7% in African Americans, P = .23). Despite slightly better response rates to neoadjuvant chemotherapy, Caucasian patients did not have higher 3‐year local control rates (70% in Caucasians vs 64% in African Americans, P = .73). However, there was a trend toward higher 3‐year overall survival in Caucasian versus African American patients (73% in Caucasians vs 55% in African Americans, P = .09) and higher distant metastasis‐free survival (60% in Caucasians vs 40% in African Americans, P = .19).

CONCLUSIONS:

This study is among the largest to examine patients with IBC by race. Being Caucasian or African American did not appear to impact treatment adherence. However, African American patients tended to have poorer response to standard treatment and worse outcome than Caucasian patients. Cancer 2011;. © 2011 American Cancer Society.     

Identification of differentially expressed genes in breast tumors from African American compared with Caucasian women

BACKGROUND:

Breast tumors from African American women have less favorable pathological characteristics and higher mortality rates than those of Caucasian women. Although socioeconomic status may influence prognosis, biological factors are also likely to contribute to tumor behavior.

METHODS:

Patients with invasive breast cancer were matched by age, grade, and estrogen receptor status; patients with benign disease were matched by age and diagnosis type. RNA from laser microdissected tumors and whole‐sectioned nonmalignant breast tissues was hybridized to HG U133A 2.0 microarrays. Data were analyzed using Partek Genomics Suite using a cutoff of P < .001, >1.5‐fold change, and results were validated by quantitative real‐time polymerase chain reaction.

RESULTS:

Clinicopathological factors did not differ significantly between groups for age at diagnosis, tumor size or stage, lymph node or human epidermal growth receptor 2 status, intrinsic subtype, or mortality. Two‐way analysis of the tumor specimens revealed 25 probes representing 23 genes differentially expressed between populations; hierarchical clustering classified 24 of 26 African American women and 25 of 26 Caucasian women correctly. In the nonmalignant specimens, 15 probes representing 13 genes were differentially expressed, including 5 genes that also differed in the tumor specimens; these genes were able to correctly classify nonmalignant breast specimens from 20 of 22 of African American women and all of the Caucasian women.

CONCLUSIONS:

Despite matching of tumors by pathological characteristics, molecular profiles differed between African American women and Caucasian women in both invasive tumors and benign breast tissues. These differentially expressed genes, including CRYBB2, PSPHL, and SOS1, are involved in cellular growth and differentiation, invasion, metastasis, and immune response and thus may contribute to the poor outcome in African American women. Cancer 2012;. © 2011 American Cancer Society.     

Age‐stratified 5‐year risks of cervical precancer among women with enrollment and newly detected HPV infection

It is unclear whether a woman's age influences her risk of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) upon detection of HPV. A large change in risk as women age would influence vaccination and screening policies. Among 972,029 women age 30–64 undergoing screening with Pap and HPV testing (Hybrid Capture 2, Qiagen, Germantown, MD) at Kaiser Permanente Northern California (KPNC), we calculated age‐specific 5‐year CIN3+ risks among women with HPV infections detected at enrollment, and among women with “newly detected” HPV infections at their second screening visit. Women (57,899, 6.0%) had an enrollment HPV infection. Among the women testing HPV negative at enrollment with a second screening visit, 16,724 (3.3%) had a newly detected HPV infection at their second visit. Both enrollment and newly detected HPV rates declined with age (p < 0.001). Women with enrollment versus newly detected HPV infection had higher 5‐year CIN3+ risks: 8.5% versus 3.9%, (p < 0.0001). Risks did not increase with age but declined slightly from 30–34 years to 60–64 years: 9.4% versus 7.4% (p = 0.017) for enrollment HPV and 5.1% versus 3.5% (p = 0.014) for newly detected HPV. Among women age 30–64 in an established screening program, women with newly detected HPV infections were at lower risk than women with enrollment infections, suggesting reduced benefit vaccinating women at older ages. Although the rates of HPV infection declined dramatically with age, the subsequent CIN3+ risks associated with HPV infection declined only slightly. The CIN3+ risks among older women are sufficiently elevated to warrant continued screening through age 65.     

Human papillomavirus type 52 polymorphism and high‐grade lesions of the uterine cervix

The association between polymorphism of human papillomavirus type 52 (HPV52) and high‐grade cervical intraepithelial neoplasia (CIN2,3) was investigated in Canadian women. HPV‐52‐positive endocervical specimens collected from 216 women selected from a total of 3,614 participants recruited in two case‐control and two cohort studies conducted in Canada, were further analyzed by PCR‐sequencing of the LCR and E6 gene. Overall, the HPV52 LCR prototype was detected more frequently in Caucasian women (69 of 132, 52.3%, 95% confidence interval (CI): 43.8%–60.6%) than in non‐Caucasian women (15 of 48, 31.3%, 95% CI 19.9%–45.4%). In two cohort studies, HPV52 prototype was detected in seven of 15 (46.7%, 95% CI 24.8–69.9) HPV52 persistent infections and 14 of 35 (40.0%, 95% CI 25.5–56.5) transient infections (p = 0.76). In two case‐control studies, 30 participants did not have CIN, 18 had low‐grade CIN (CIN1), 64 had CIN2,3, seven had cervical cancer and the diagnosis was undefined for 27 women. Variant MTL‐52‐LCR‐02 was detected more frequently in women with cancer (28.6%, 95% CI 7.6%–64.8%) than in women without cancer or CIN2,3 (0%, 95% CI 0.0%–9.2%; p = 0.015). CIN2,3 risk was significantly associated with a deletion at nucleotide position 7695 in the LCR (OR 4.9, 95% CI 1.2–20.8), the T7744C variation in the LCR (OR 5.7, 95% CI 1.1–32.0), and the K93R variation in E6 (OR 6.9, 95% CI 1.3–36.8), after adjusting for age, detection of HPV16 or 18 and study site. These findings indicate that HPV52 polymorphism influences risk of CIN‐2,3 and possibly invasive cancer.     

Viral load and short‐term natural history of type‐specific oncogenic human papillomavirus infections in a high‐risk cohort of midadult women

Oncogenic human papillomavirus (HPV) viral load may inform the origin of newly detected infections and characterize oncogenic HPV natural history in midadult women. From 2007 to 2011, we enrolled 521 25–65‐year‐old‐female online daters and followed them triannually with mailed health and sexual behavior questionnaires and kits for self‐sampling for PCR‐based HPV DNA testing. Samples from oncogenic HPV positive women were selected for type‐specific DNA load testing by real‐time PCR with adjustment for cellularity. Linear or logistic regression models were used to evaluate relationships between viral levels, health and sexual behavior, and longitudinal oncogenic HPV detection. Type‐specific viral levels were borderline significantly higher in oncogenic HPV infections that were prevalent versus newly detected (p = 0.092), but levels in newly detected infections were higher than in infections redetected after intercurrent negativity (p < 0.001). Recent sex partners were not significantly associated with viral levels. Compared with prevalent infections detected intermittently, the likelihood of persistent (OR = 4.31, 95% CI: 2.20–8.45) or single‐time (OR = 1.32, 95% CI: 1.03–1.71) detection increased per 1‐unit increase in baseline log₁₀ viral load. Viral load differences between redetected and newly detected infections suggest a portion of new detections were due to new acquisition, although report of recent new sex partners (a potential marker of new infection) was not predictive of viral load; oncogenic HPV infections in midadult women with new partners likely represent a mix of new acquisition and reactivation or intermittent detection of previous infection. Intermittent detection was characterized by low viral levels, suggesting that intermittent detection of persisting oncogenic HPV infection may be of limited clinical significance.     

Trichomonas vaginalis (TV) and human papillomavirus (HPV) infection and the incidence of cervical intraepithelial neoplasia (CIN) grade III

The temporal relationship between cervical infection with Trichomonas vaginalis (TV) or human papillomavirus (HPV) and the incidence rate of cervical intraepithelial neoplasia grade three (CIN III) was examined in a cohort of 43,016 Norwegian women. From 1980 to 1989, a cervico-vaginal infection from TV and HPV was diagnosed cytologically in 988 and 678 women, respectively. During the 181,240 person-years of observation, 440 cases of CIN III/cervical cancer developed. The age-adjusted incidence rates (IR) of CIN III were 225 per 100,000 person-years among women with no cytologic evidence of infection,459 among women with TV infection, and 729 among women with HPV infection. A multiple regression model yielded a relative rate (RR) of CIN III of 2.1 (95 percent confidence interval [CI]=1.3–3.4) among women with TV infection and 3.5 (CI=1.9–6.6) among women with HPV infection, compared with women with neither infection. As CIN can be misclassified as HPV infection, the entry Pap-smears of 10 women with HPV infection who later developed CIN III were re-examined. Excluding the four discordant cases with the corresponding person-years decreased the RR of CIN III to 2.1 (CI=0.9–4.8). Our report demonstrates the limitations of studies that rely only on cytologic detection of HPV infection. Nevertheless, the results support the hypothesis that HPV is a causal factor for CIN III lesions, and also display an association between TV infection and cervical neoplasia.Dr Gram is a research fellow of the Norwegian Cancer Society. This study was supported in part by a grant from the Aakre Foundation for the fighting of cancer and a grant from the University of Tromsö. A summary of this paper was presented at the American Public Health Association Annual Meeting, Atlanta, GA, USA, 10–14 November 1991.     

The national landscape of human papillomavirus‐associated oropharynx squamous cell carcinoma

The head and neck squamous cell carcinoma (HNC) landscape is evolving with human papillomavirus (HPV) being a rising cause of oropharynx carcinoma (OPC). This study seeks to investigate a national database for HPV‐associated oropharynx carcinoma (HPV‐OPC). Using the National Cancer Data Base, we analyzed 22,693 patients with HPV‐OPC and known HPV status. Chi‐square tests and logistic regression models were utilized to examine differences between HPV positive and HPV negative OPC. 14,805 (65.2%) patients were HPV positive. Mean age at presentation was 58.4 years with HPV‐HNC patients being 2.8 years younger compared to the HPV‐negative cohort (58.4 vs. 61.2 years, p < 0.001). 67.6% of white patients were HPV‐positive compared to 42.3% of African American patients and 57.1% of Hispanics (p < 0.001). When combining race and socioeconomic status (SES), we found African American patients in high SES groups had HPV‐OPC prevalence that was significantly higher than African American patients in low SES groups (56.9% vs. 36.3%, p < 0.001). Geographic distribution of HPV‐OPC was also analyzed and found to be most prevalent in Western states and least prevalent in the Southern states (p < 0.001). The distribution of HPV‐OPC is variable across the country and among racial and socioeconomic groups. A broad understanding of these differences in HPV‐OPC should drive educational programs and improve clinical trials that benefit both prevention and current treatments.     

Persistence of HPV infection and risk of high-grade cervical intraepithelial neoplasia in a cohort of Colombian women

Little is known about the dynamics of human papillomavirus (HPV) infection and subsequent development of high-grade cervical intraepithelial neoplasia (CIN2/3), particularly in women >30 years of age. This information is needed to assess the impact of HPV vaccines and consider new screening strategies. A cohort of 1728 women 15–85 years old with normal cytology at baseline was followed every 6 months for an average of 9 years. Women with squamous intraepithelial lesions were referred for biopsy and treatment. The Kaplan–Meier method was used to estimate the median duration of infection and Cox regression analysis was undertaken to assess determinants of clearance and risk of CIN2/3 associated with HPV persistence. No difference in the likelihood of clearance was observed by HPV type or woman''s age, with the exception of lower clearance for HPV16 infection in women under 30 years of age. Viral load was inversely associated with clearance. In conclusion, viral load is the main determinant of persistence, and persistence of HPV16 infections carry a higher risk of CIN2/3.     

Progression of HPV infection to detectable cervical lesions or clearance in adult women: Analysis of the control arm of the VIVIANE study

The control arm of the phase III VIVIANE (Human PapillomaVIrus: Vaccine Immunogenicity ANd Efficacy; NCT00294047) study in women >25 years was studied to assess risk of progression from cervical HPV infection to detectable cervical intraepithelial neoplasia (CIN). The risk of detecting CIN associated with the same HPV type as the reference infection was analysed using Kaplan–Meier and multivariable Cox models. Infections were categorised depending upon persistence as 6‐month persistent infection (6MPI) or infection of any duration. The 4‐year interim analysis included 2,838 women, of whom 1,073 (37.8%) experienced 2,615 infections of any duration and 708 (24.9%) experienced 1,130 6MPIs. Infection with oncogenic HPV types significantly increased the risk of detecting CIN grade 2 or greater (CIN2+) versus non‐oncogenic types. For 6MPI, the highest risk was associated with HPV‐33 (hazard ratio [HR]: 31.9 [8.3–122.2, p < 0.0001]). The next highest risk was with HPV‐16 (21.1 [6.3–70.0], p < 0.0001). Similar findings were seen for infections of any duration. Significant risk was also observed for HPV‐18, HPV‐31, and HPV‐45. Concomitant HPV infection or CIN grade 1 or greater associated with a different oncogenic HPV type increased risk. Most women (79.3%) with an HPV infection at baseline cleared detectable infections of any duration, and 69.9% cleared a 6MPI. The risk of progression of HPV infection to CIN2+ in women >25 years in this study was similar to that in women 15–25 years in PATRICIA.     

Disparities in medical care among commercially insured patients with newly diagnosed breast cancer

BACKGROUND:

African‐American women have increased breast cancer mortality compared with white women. Diagnostic and treatment gaps may contribute to this disparity.

METHODS:

In this retrospective, longitudinal cohort study, Southern US health plan claims data and linked medical charts were used to identify racial disparities in the diagnoses, treatment, and mortality of commercially insured women with newly diagnosed breast cancer. White women (n = 476) and African‐American women (n = 99) with newly diagnosed breast cancer were identified by breast cancer claims codes (International Classification of Diseases, Ninth Revision, Clinical Modification codes 174, 233.0, 238.3, and 239.3) between January 2000 and December 2004. Race, diagnoses (breast cancer stage, estrogen/progesterone receptor [ER/PR]‐positive status), treatment (breast‐conserving surgery, antiestrogen therapy, and chemotherapy interruption or reduction), and all‐cause mortality were assessed from medical charts. Multivariate regression analyses were adjusted for age, geography, and socioeconomic status to test the association of race with diagnoses/treatment.

RESULTS:

White women were older (P < .001) and had higher rates of diagnosis at stage 0/I (55.2% vs 38.4%; P < .05) than African‐American women. More white women had positive ER/PR status (75% vs 56% African‐American; P = .001) and received antiestrogen therapy if they were positive (37.2% vs 27.3% African‐American; P < .001). White women received slightly more breast‐conserving surgery and chemotherapy dose modification than African‐American women (P value nonsignificant). African‐American women had a higher mortality rate (8.1%) than white women (3.6%; P = .06). In adjusted analyses, African‐American women were diagnosed at later stages (odds ratio, 1.71; P = .02), and white women received more antiestrogen therapy (odds ratio, 2.1; P = .03).

CONCLUSIONS:

Disparities in medical care among patients with newly diagnosed breast cancer were evident between African‐American women and white women despite health plan insurance coverage. Interventions that address the gaps identified are needed. Cancer 2010. © 2010 American Cancer Society.