Lori Kamemoto

Anal Human Papillomavirus Infection in Women and Its Relationship with Cervical Infection

Human papillomavirus (HPV), the primary cause of cervical cancer, is also associated with the development of anal cancer. Relatively little is known about the epidemiology of anal HPV infection among healthy females and its relationship to cervical infection. We sought to characterize anal HPV infection in a cohort of adult women in Hawaii. Overall, 27% (372 of 1,378) of women were positive for anal HPV DNA at baseline compared with 29% (692 of 2,372) with cervical HPV DNA. Among women with paired anal and cervical samples, anal infection without accompanying cervical infection was observed in 14% (190 of 1,363). Concurrent anal and cervical HPV infections were observed in 13% (178 of 1,363) of women. Women with cervical HPV infection had >3-fold increased risk of concurrent anal infection. Concurrent anal and cervical HPV infection was most prevalent among the youngest women and steadily decreased through age 50 years. By contrast, the prevalence of anal infection alone remained relatively steady in all age groups. Compared with cervical infections, the overall distribution of HPV genotypes in the anus was more heterogeneous and included a greater proportion of nononcogenic types. A high degree of genotype-specific concordance was observed among concurrent anal and cervical infections, indicating a common source of infection. Nevertheless, the association of anal intercourse with anal HPV infection was limited to those women without accompanying cervical infection. The relationship of anal to cervical infection as described in this study has implications for the development of anal malignancies in women.

Prevalence, Acquisition, and Clearance of Cervical Human Papillomavirus Infection among Women with Normal Cytology: Hawaii Human Papillomavirus Cohort Study

Few natural history studies of cervical human papillomavirus (HPV) incidence and duration have been conducted among older women, especially from multiethnic populations. Viral and nonviral determinants of HPV acquisition and clearance were examined among 972 sexually active women, ages 18 to 85 years, recruited from clinics on Oahu, Hawaii, and followed for a mean duration of 15 months (range, 2-56 months). Interviews and cervical cell specimens for cytology and HPV DNA detection by PCR, using the PGMY09/PGMY11 primer system, were obtained at baseline and at 4-month intervals. The prevalence of cervical HPV infection was 25.6% at study entry. A total of 476 incident genotype-specific infections were observed during the follow-up period. The incidence of high-risk (HR) HPV types (9.26 per 1,000 woman-months) was similar to low-risk (LR) HPV types (8.24 per 1,000 woman-months). The most commonly acquired HR-HPV types were HPV-52, HPV-16, and HPV-31; and their incidence was increased significantly with a coexisting cervical HPV infection. Cervical HPV acquisition decreased with age, income, and long-term use of oral contraceptives and increased with number of sexual partners, use of hormonal creams, alcohol drinking, and condom use by a sexual partner. Cohort participants cleared 265 of the 476 incident infections during follow-up. LR-HPV infections cleared more rapidly than did HR-HPV infections (median, 180 days versus 224 days). Clearance times were enhanced among older women and women with multiple infections. Our data suggest several viral and nonviral determinants of cervical HPV acquisition and clearance that might be used in cervical cancer prevention programs.

Acquisition of Anal Human Papillomavirus (HPV) Infection in Women: the Hawaii HPV Cohort Study

BACKGROUND The majority of anal cancer is associated with human papillomavirus (HPV) infection, yet little is known about womens risk of acquisition of anal HPV infection. METHODS Risk factors for the acquisition of anal HPV infection were examined in a longitudinal cohort study of 431 women, via repeated measurement of HPV DNA. RESULTS Seventy percent of women were positive for anal HPV infection at one or more clinic visits from baseline through a follow-up period that averaged 1.3 years. The incidence of a high-risk (HR) infection was 19.5 (95% confidence interval [CI], 16.0-23.6) per 1000 woman-months. The most common incident HR HPV types were HPV-53, -52 and -16. The presence of an HR anal HPV infection at baseline increased the risk of an incident anal infection by 65%. Baseline HR cervical HPV infection also predicted the acquisition of an HR anal HPV infection (odds ratio, 1.81 [95% CI, 1.09-3.02]). Nonviral risk factors for acquisition of HR HPV infection included younger age, lower socioeconomic status, greater lifetime number of sexual partners, past use of hormones, and condom use. CONCLUSIONS The results of this study suggest that womens risk of anal HPV infection is as common as their risk of cervical HPV infection.

Sequential Acquisition of Human Papillomavirus (HPV) Infection of the Anus and Cervix: The Hawaii HPV Cohort Study

BACKGROUND Relatively little is known about the epidemiology of anal human papillomavirus (HPV) infection in healthy women and its association with cervical HPV infection. METHODS he association of an incident cervical (or anal) HPV infection with the subsequent risk of a genotype-concordant incident anal (or cervical) HPV infection was examined in a longitudinal cohort study of 751 sexually active women. Age-adjusted hazard ratios, obtained using Cox regression, served as measurements of relative risk (RR). RESULTS Among women, the RR of acquiring an anal HPV infection after a cervical infection with HPV of the same genotype was 20.5 (95% confidence interval, 16.3-25.7), and the RR of acquiring a cervical HPV infection after an anal infection with HPV of the same genotype was 8.8 (95% confidence interval, 6.4-12.2), compared with women without a previous anal/cervical infection with HPV of a concordant genotype. RRs varied by phylogenetic species, with HPV alpha3/alpha15 and alpha1/alpha8/alpha10 types having a greater likelihood than other types of HPV infecting the anus among women with a previous infection at the cervix with HPV of the same genotype. CONCLUSIONS It appears common for anal and cervical HPV infections to occur consecutively. The high degree of genotype-specific concordance suggests that the cervix (vagina) and anus may serve as reservoirs for HPV infection at the other anatomical site.

Duration and Clearance of Anal Human Papillomavirus (HPV) Infection among Women: The Hawaii HPV Cohort Study

BACKGROUND The association of anal cancer with human papillomavirus (HPV) infection is well established; however, little is known about the epidemiology of anal HPV in healthy women. We investigated patterns of duration and clearance of anal HPV infection in a cohort of healthy women in Hawaii. METHODS Viral and nonviral determinants of anal HPV clearance were examined in a longitudinal cohort study of 431 sexually active women. At baseline and at 4-month intervals, interviews were conducted and cervical and anal cell specimens were obtained for detection of HPV DNA. RESULTS Of the 431 women, 50% experienced a total of 414 incident anal HPV infections, reported at 1 clinic visits from baseline through a follow-up period of average duration of 1.2 years. Of these infections, 58% cleared during follow-up. The clearance rate for a high-risk anal infection was 9.2 per 100 woman-months (95% confidence interval [CI], 6.9-11.9 per 100 woman-months), with a median duration of 150 days (95% CI, 132-243 days). The slowest clearing high-risk HPV types were HPV-59 (median clearance time, 350 days) and HPV-58 (median clearance time, 252 days). The median clearance times for HPV-16 and HPV-18, the predominant types associated with anal cancer, were 132 days and 212 days, respectively. Nonviral factors that delayed clearance of anal HPV included douching, long-term tobacco smoking, and anal sex. CONCLUSIONS The majority of anal HPV infections resolve in a relatively short time. Although anal HPV is commonly acquired in healthy women, its rapid clearance suggests limited efficacy of HPV testing as an anal cancer screening tool.

Diet and premalignant lesions of the cervix: evidence of a protective role for folate, riboflavin, thiamin, and vitamin B12

Objective: A case–control study was conducted among a population of multiethnic women identified from clinics on Oahu, Hawaii between 1992 and 1996 to explore the relationship between diet and cervical dysplasia. Methods: Two-hundred and fourteen women with biopsy-confirmed high and low grade squamous intraepithelial lesions of the cervix (SIL) and 271 controls were identified. Exfoliated cervical cells were collected for HPV DNA testing. Surveys were administered to assess non-dietary risk factors and intake of nutrients from over 250 specific food items as well as nutritional supplements. Results: Riboflavin and thiamin from food sources, vitamin B12 supplements, and total (food and supplements) folate displayed inverse, dose-responsive associations with high-grade SIL (HSIL). Riboflavin from food sources and total folate also demonstrated inverse, dose-responsive associations with low-grade SIL (LSIL). The odds ratios for LSIL and HSIL were reduced by 50–90% for the highest compared to the lowest levels of intake of these nutrients. A number of major food sources of these vitamins, including all types of breads, bran cereal, and fruit juice, also demonstrated inverse associations with HSIL. There was some evidence that the increased risk of HSIL associated with low nutrient intake was most pronounced among drinkers and smokers. Conclusions: This investigation provides evidence that thiamin, riboflavin, folate, and vitamin B12 may play a protective role in cervical carcinogenesis.

Near-Infrared Micro-Raman Spectroscopy for in Vitro Detection of Cervical Cancer

Near-infrared Raman spectroscopy is a powerful analytical tool for detecting critical differences in biological samples with minimum interference in the Raman spectra from the native fluorescence of the samples. The technique is often suggested as a potential screening tool for cancer. In this article we report in vitro Raman spectra of squamous cells in normal and cancerous cervical human tissue from seven patients, which have good signal-to-noise ratio and which were found to be reproducible. These preliminary results show that several Raman features in these spectra could be used to distinguish cancerous cervical squamous cells from normal cervical squamous cells. In general, the Raman spectra of cervical cancer cells show intensity differences compared to those of normal squamous cell spectra. For example, several well-defined Raman peaks of collagen in the 775 to 975 cm−1 region are observed in the case of normal squamous cells, but these are below the detection limit of normal Raman spectroscopy in the spectra of invasive cervical cancer cells. In the high frequency 2800 to 3100 cm−1 region, it is found that the peak area under the CH stretching band is lower by a factor of approximately six in the spectra of cervical cancer cells as compared with that of the normal cells. The Raman chemical maps of regions of cancer and normal cells in the cervical epithelium made from the spectral features in the 775 to 975 cm−1 and 2800 to 3100 cm−1 regions are also found to show good correlation with each other.

Contraceptive Efficacy of Oral and Transdermal Hormones When Co-Administered With Protease Inhibitors in HIV-1―Infected Women: Pharmacokinetic Results of ACTG Trial A5188

Background:Pharmacokinetic (PK) interactions between lopinavir/ritonavir (LPV/r) and transdermally delivered ethinyl estradiol (EE) and norelgestromin (NGMN) are unknown. Methods:Using a standard noncompartmental PK analysis, we compared EE area under the time-concentration curve (AUC) and NGMN AUC during transdermal contraceptive patch administration in HIV-1-infected women on stable LPV/r to a control group of women not on highly active antiretroviral therapy (HAART). In addition, EE AUC after a single dose of a combination oral contraceptive pill including EE and norethindrone was measured before patch placement and was compared with patch EE AUC in both groups. Contraceptive effects on LPV/r PKs were estimated by measuring LPV/r AUC at baseline and during week 3 of patch administration. Results:Eight women on LPV/r, and 24 women in the control group were enrolled. Patch EE median AUC0−168 h was 45% lower at 6010.36 pg·h·mL−1 in those on LPV/r versus 10911.42 pg·h·mL−1 in those on no HAART (P = 0.064). Pill EE median AUC0−48 hours was similarly 55% lower at 344.67 pg·h·mL−1 in those on LPV/r versus 765.38 pg·h·mL−1 in those on no HAART (P = 0.003). Patch NGMN AUC0−168 h however, was 138.39 ng·h·mL−1, 83% higher in the LPV/r group compared with the control AUC of 75.63 ng·h·mL−1 (P = 0.036). After 3 weeks on the patch, LPV AUC0−8 h decreased by 19%, (P = 0.156). Conclusions:Although PKs of contraceptive EE and NGMN are significantly altered with LPV/r, the contraceptive efficacy of the patch is likely to be maintained. Larger studies are indicated to fully assess contraceptive efficacy versus risks of the transdermal contraceptive patch when co-administered with protease inhibitors.

Novel Micro-Cavity Substrates for Improving the Raman Signal from Submicrometer Size Materials

A novel and simple method for improving the detection limit of conventional Raman spectra using a micro-Raman system and picoliter volumes is presented. A micro-cavity in a reflecting metal substrate uses various mechanisms that collectively improve the entire Raman spectrum from the sample. A micro-cavity with a radius of several micrometers acts as a very effective device that provides multiple excitation of the sample with the laser and couples the forward-scattered Raman photons toward the collection optics in the back-scattered Raman geometry. One of the important features of the micro-cavity substrate is that it enhances the entire Raman spectrum of the molecules under investigation and maintains the relative intensity ratios of the various Raman bands. This feature of maintaining the overall integrity of the Raman features during signal enhancement makes the micro-cavity substrate ideal for forensic science applications for chemical detection of residual traces and other applications requiring low sample concentrations. The spectra measured in these cavities are also observed to be highly reproducible and reliable. A simple method for fabricating micro-cavity substrates with precise sizes and shapes is described. It is further shown that micro-cavities coated with nanofilms of gold take advantage of both surface-enhanced Raman scattering (SERS) and micro-cavity methods and also significantly improve sample detection limits.

Hawaii Cohort Study of Serum Micronutrient Concentrations and Clearance of Incident Oncogenic Human Papillomavirus Infection of the Cervix

The degree to which the resolution of human papillomavirus (HPV) infection parallels exposure to other factors, particularly those related to nutritional status, is a relatively unexplored area of research. We established a cohort of women for long-term follow-up to examine the association of serum retinol, carotenoid, and tocopherol concentrations with the clearance of incident cervical HPV infection. Interviews and biological specimens were obtained at baseline and at 4-month intervals. At each visit, a cervical cell specimen for HPV DNA analysis and cytology and a fasting blood sample to measure micronutrient levels were collected. A Cox proportional hazards model was used to study the relationship between clearance of 189 incident (type-specific) oncogenic HPV infections and the levels of 20 serum micronutrients among 122 women. Higher circulating levels of trans-zeaxanthin, total trans-lutein/zeaxanthin, cryptoxanthin (total and beta), total trans-lycopene and cis-lycopene, carotene (alpha, beta, and total), and total carotenoids were associated with a significant decrease in the clearance time of type-specific HPV infection, particularly during the early stages of infection (<or=120 days). HPV clearance time was also significantly shorter among women with the highest compared with the lowest serum levels of alpha-tocopherol and total-tocopherol, but significant trends in these associations were limited to infections lasting <or=120 days. Clearance of persistent HPV infection (lasting >120 days) was not significantly associated with circulating levels of carotenoids or tocopherols. Results from this investigation support an association of micronutrients with the rapid clearance of incident oncogenic HPV infection of the uterine cervix.