Diffuse Reflectance Spectroscopy of Epithelial Tissue with a Smart Fiber-optic Probe

Diffuse reflectance spectroscopy (DRS) with a fiber-optic probe can noninvasively quantify the optical properties of epithelial tissues and has shown the potential as a cost-effective, fast and sensitive tool for diagnosis of early precancerous changes in the cervix and oral cavity. However, current DRS systems are susceptible to several sources of systematic and random errors, such as uncontrolled probe-to-tissue pressure and lack of a real-time calibration that can significantly impair the measurement accuracy, reliability and validity of this technology as well as its clinical utility. In addition, such systems use bulky, high power and expensive optical components which impede their widespread use in low- and middle-income countries (LMICs) where epithelial cancer related death is disproportionately high. In this paper we report a portable, easy-to-use and low cost, yet accurate and reliable DRS device that can aid in the screening and diagnosis of oral and cervical cancer. The device uses an innovative smart fiber-optic probe to eliminate operator bias, state-of-the-art photonics components to reduce size and power consumption, and automated software to reduce the need of operator training. The device showed a mean error of 1.4 ± 0.5% and 6.8 ± 1.7% for extraction of phantom absorption and reduced scattering coefficients, respectively. A clinical study on healthy volunteers indicated that a pressure below 1.0 psi is desired for oral mucosal tissues to minimize the probe effects on tissue physiology and morphology

Emerging Optical Techniques for Detection of Oral, Cervical and Anal Cancer in Low-Resource Settings

Cancers of the oral and anogenital regions are a growing global health problem that disproportionately impact women and men living in developing countries. The high death rate in developing countries is largely due to the fact that these countries do not have the appropriate medical infrastructure and resources to support the organized screening and diagnostic programs that are available in the developed world. Emerging optical diagnostics techniques, such as optical spectroscopy, reflectance imaging, and fluorescence imaging, are noninvasive techniques that are sensitive to multiple cancer biomarkers and have shown the potential as a cost–effective and fast tool for diagnosis of early precancerous changes in the cervix, oral cavity and anus. This paper provides a review of current strategies for prevention, screening and diagnostic tests of oral, cervical and anal cancers and development in optical diagnostic techniques that could potentially be used to improve current practice in resource–limited settings

Reaching women in the Peruvian Andes through cervical cancer screening campaigns: assessing attitudes of stakeholders and patients

BACKGROUND: Peru is characterized by high cervical cancer incidence and mortality rates. The country also experiences significant gaps in quality cervical cancer screening coverage for the population. OBJECTIVE: This descriptive mixed methods study conducted in Cusco, Peru, aimed to assess the attitudes and perceptions of medical staff, health care workers, and patients toward a cervical cancer screening program that included both clinic-based and community outreach services conducted by a nongovernmental organization clinic (CerviCusco). The study also explored patient knowledge and attitudes around cervical cancer and about the human papillomavirus (HPV) to inform patient education efforts. METHODS: The study employed structured interviews with key informants (n=16) primarily from CerviCusco, which provides cervical cancer prevention, screening, diagnosis and treatment services, and surveys with a sample of patients (n=30) receiving services at the clinic and at screening campaigns. RESULTS: The majority of key informant medical staff participants felt that the general public had a very negative view of government health services. One theme running throughout the interviews was the perception that the general population lacked a culture of preventive health care and would wait until symptoms were severe before seeking treatment. Regarding services that were received by patients at CerviCusco, the participants responded that the prices were reasonable and more affordable than some private clinics. Patients attending the rural health campaigns liked that the services were free and of good quality. CONCLUSION: CerviCusco has demonstrated its capacity to provide screening outreach campaigns to populations who had not previously had access to liquid-based cytology services. The finding that patients had generally low levels of knowledge about cervical cancer and the HPV vaccine prompted the development of culturally and linguistically appropriate educational and promotional materials to improve the educational component of the periodic campaigns conducted primarily in rural areas of Andean Peru

Large-scale analysis of protein expression changes in human keratinocytes immortalized by human papilloma virus type 16 E6 and E7 oncogenes

<p>Abstract</p> <p>Background</p> <p>Infection with high-risk type human papilloma viruses (HPVs) is associated with cervical carcinomas and with a subset of head and neck squamous cell carcinomas. Viral E6 and E7 oncogenes cooperate to achieve cell immortalization by a mechanism that is not yet fully understood. Here, human keratinocytes were immortalized by long-term expression of HPV type 16 E6 or E7 oncoproteins, or both. Proteomic profiling was used to compare expression levels for 741 discrete protein features.</p> <p>Results</p> <p>Six replicate measurements were performed for each group using two-dimensional difference gel electrophoresis (2D-DIGE). The median within-group coefficient of variation was 19–21%. Significance of between-group differences was tested based on Significance Analysis of Microarray and fold change. Expression of 170 (23%) of the protein features changed significantly in immortalized cells compared to primary keratinocytes. Most of these changes were qualitatively similar in cells immortalized by E6, E7, or E6/7 expression, indicating convergence on a common phenotype, but fifteen proteins (~2%) were outliers in this regulatory pattern. Ten demonstrated opposite regulation in E6- and E7-expressing cells, including the cell cycle regulator p16^INK4a; the carbohydrate binding protein Galectin-7; two differentially migrating forms of the intermediate filament protein Cytokeratin-7; HSPA1A (Hsp70-1); and five unidentified proteins. Five others had a pattern of expression that suggested cooperativity between the co-expressed oncoproteins. Two of these were identified as forms of the small heat shock protein HSPB1 (Hsp27).</p> <p>Conclusion</p> <p>This large-scale analysis provides a framework for understanding the cooperation between E6 and E7 oncoproteins in HPV-driven carcinogenesis.</p

Cultural Beliefs and Understandings of Cervical Cancer among Mexican Immigrant Women in Southeast Georgia

Rural Mexican immigrant women in the U.S. are infrequently screened and experience health disparities from cervical cancer. We explored cancer-related cultural beliefs in this population. We administered a cross-sectional survey to 39 Mexican immigrant women due for screening. We conducted univariate and bivariate analyses of participants’ characteristics, Pap test history, cancer-related knowledge and beliefs, and cultural consensus analysis about causes of cervical cancer and barriers to screening. For all the cultural consensus tasks, there was consensus (Eigenratios \u3e3:1) among survey participants. Comparing the rankings of risk factor clusters, clusters related to sexual behaviors were ranked more severely than clusters related to genetic or other behavioral factors. There was agreement on ideas of cervical cancer causation and barriers to screening among these women. Hence, improved methods of disseminating important health information and greater access to care are needed, particularly in relationship to stigma about sex and birth control practice

Human papillomavirus seroprevalence and seroconversion following baseline detection of nine human papillomavirus types in young women

Background: Estimates of the humoral immune response to incident human papillomavirus (HPV) infections are limited. Methods: In this post hoc analysis of 3875 women aged 16-23 years from a 4-valent HPV vaccine trial (NCT00092482), HPV seroprevalence on day 1 was measured with a 9-valent HPV (HPV 6/11/16/18/31/33/45/ 52/58) competitive Luminex immunoassay and compared with cervical/external genital HPV detection by po-lymerase chain reaction. In the control group, among women who were HPV DNA-negative on day 1, sero-conversion following initial HPV detection was estimated using Kaplan-Meier methods. Results: Type-specific HPV seropositivity among women with no day 1 cervical/external genital HPV detection was 0.6%-3.6%. Women with any 9-valent HPV (9vHPV) cervical/external genital detection (796/3875; 20.5%) had concordant seropositivity ranging from 13.4% (HPV 45) to 38.5% (HPV 6). Among women in the control group who were negative for all HPV types on day 1, seroconversion by month 30 after initial detection ranged from 29% (HPV 45) to 75% (HPV 16). Conclusions: Humoral immune response to HPV is variable and dynamic, depending on type-specific exposure. This longitudinal analysis provides insight into the relationship between incident infection and seropositivity

Effect of the human papillomavirus (HPV) quadrivalent vaccine in a subgroup of women with cervical and vulvar disease: retrospective pooled analysis of trial data

Objectives To determine the effect of human papillomavirus (HPV) quadrivalent vaccine on the risk of developing subsequent disease after an excisional procedure for cervical intraepithelial neoplasia or diagnosis of genital warts, vulvar intraepithelial neoplasia, or vaginal intraepithelial neoplasia

Imiquimod 3.75% Cream Applied Daily to Treat Anogenital Warts: Combined Results from Women in Two Randomized, Placebo-Controlled Studies

Objective. To evaluate if new imiquimod formulations using a shorter treatment duration are safe and efficacious to treat anogenital warts. Methods. In two studies 534 women ≥12 years of age (mean 33.4) with 2–30 warts (mean 7.9) and total wart area ≥10 mm2 (mean 166.3) were randomized (1 : 2 : 2) to placebo (106), imiquimod 2.5% (212) or 3.75% (216) creams applied once daily until complete clearance or a maximum of 8 weeks. Results. For placebo, imiquimod 2.5% and 3.75%, respectively, complete clearance of all warts was achieved in 14.2%, 28.3%, and 36.6% of women (intent-to-treat, P = 0.008 imiquimod 2.5%, and P < 0.001 3.75% versus placebo). Mean changes in wart counts were −10.7%, −50.9%, and −63.5% (per-protocol, P < 0.001 each active versus placebo) and safety-related discontinuation rates 0.9%, 1.4%, and 2.3%. Conclusions. Imiquimod 3.75% applied daily for up to 8 weeks was well tolerated and superior to placebo in treating women with external anogenital warts

Incidence, duration, and reappearance of type-specific cervical human papillomavirus infections in young women

Background: We describe the incidence and duration of cervical human papillomavirus (HPV) infection episodes along with the risk of infection reappearance following a period of nondetection. Methods:Women (1,788) ages 16 to 23 years underwent cytologic testing and PCR-based testing of cervical swab samples for HPV DNA (HPV-16/18/31/33/35/45/52/58/59) at ?6-month intervals for up to 4 years in the context of a phase 3 clinical trial (placebo arm). HPV type - specific incidence rates were estimated per 100 person-years. Duration of type-specific cervical infection episodes and risk of reappearance following a period of nondetection were estimated using Kaplan-Meier methods. Results: HPV-16 exhibited the highest (5.9), and HPV-35 and HPV-33 exhibited the lowest (1.0) incidence rates per 100 person-years. Mean cervical infection durations ranged from 13 months for HPV-59 to 20 months for HPV-16 and 58 (with ongoing infections censored at the time of treatment, if done). The risk of cervical infection reappearance within ?3 years following a period of nondetection ranged from 0% to 16% across HPV types, with a mean of 8%. Limited evidence was found for a role of false-positive HPV tests, missed infections that were above the threshold for detection, or new acquisition of infection in accounting for patterns of infection reappearance. Conclusions: Incidence of high-risk cervical infection was observed to vary considerably more across HPV types than infection duration. A nontrivial proportion of women exhibited infection reappearance following a period of nondetection, with a potential explanation for many such events observed within this analysis being a return to detectable levels of a previously acquired infection. Impact: The risk of HPV infection reappearance following a period of nondetection has not been previously reported for individual HPV types, and this study finds that a nontrivial proportion of infected women exhibit reappearances. Future studies could ascertain subject-level factors that potentially modify the risk of infection reappearance. ©2010 AACR

Three-Year Follow-up of 2-Dose Versus 3-Dose HPV Vaccine

BACKGROUND AND OBJECTIVES: Human papillomavirus (HPV) antibody responses to the 9-valent abstract human papillomavirus (9vHPV) vaccine among girls and boys (aged 9–14 years) receiving 2- dose regimens (months 0, 6 or 0, 12) were noninferior to a 3-dose regimen (months 0, 2, 6) in young women (aged 16–26 years) 4 weeks after last vaccination in an international, randomized, open-label trial (NCT01984697). We assessed response durability through month 36. METHODS: Girls received 2 (months 0 and 6 [0, 6]: n = 301; months 0 and 12 [0, 12]: n = 151) or 3 doses (months 0,2, and 6 [0, 2, 6]: n = 301); boys received 2 doses ([0, 6]: n = 301; [0, 12]: n = 150); and young women received 3 doses ([0, 2, 6]: n = 314) of 9vHPV vaccine. Anti-HPV geometric mean titers (GMTs) were assessed by competitive Luminex immunoassay (cLIA) and immunoglobulin G-Luminex immunoassay (IgG-LIA) through month 36. RESULTS: Anti-HPV GMTs were highest 1 month after the last 9vHPV vaccine regimen dose, decreased sharply during the subsequent 12 months, and then decreased more slowly. GMTs 2 to 2.5 years after the last regimen dose in girls and boys given 2 doses were generally similar to or greater than GMTs in young women given 3 doses. Across HPV types, most boys and girls who received 2 doses (cLIA: 81%–100%; IgG-LIA: 91%–100%) and young women who received 3 doses (cLIA: 78%–98%; IgG-LIA: 91%–100%) remained seropositive 2 to 2.5 years after the last regimen dose. CONCLUSIONS: Antibody responses persisted through 2 to 2.5 years after the last dose of a 2-dose 9vHPV vaccine regimen in girls and boys. In girls and boys, antibody responses generated by 2 doses administered 6 to 12 months apart may be sufficient to induce high-level protective efficacy through at least 2 years after the second dose.Medicin