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Please note that we are unable to respond back directly to your questions or provide medical advice. Cancers of the oral and anogenital regions are a growing global health problem that disproportionately impact women and men living in developing countries. Each year, more than 650,000 new cases of head and neck cancer are diagnosed worldwide, of which over one–third are oral or oropharyngeal cancers [3,4]. Figure 2: Anal cancer (indicated with yellow arrows) and precancer (indicated with blue arrow). Hence, HPV–related cancer remains a daunting problem for public health, health care providers, insurers, patients and society. HPV is a highly contagious viral DNA organism and the most common sexually transmitted infection. Figure 3: Cervical cancer (indicated by the yellow arrows) is seen on both the anterior and posterior cervix in a 24 year old woman. Great enthusiasm surrounded the advent of these two novel primary cancer prevention vaccines.
Papanicolaou test: The Papanicolaou (Pap) smear is the most cost effective cancer screening test ever introduced. While the Pap test has decreased the rate of cervical cancer where effectively implemented, it has not been successfully introduced in resource–poor countries. Cervical cancer can be universally prevented when certain premalignant lesions of the cervix are detected early and treated adequately.
Multiple cervical lesions of varied severity are frequently seen at the same time and in the same patient (Figure 6). Because cervical cancer is preceded by premalignant cervical intraepithelial neoplasia (CIN), if detected early and treated adequately, cervical cancer can be universally prevented.
As previously discussed, the Pap test has been the gold standard cervical screening test for many years. As a consequence of the limitations of both types of Pap tests, other cervical cancer screening techniques have evolved.
In regions with poor or nonexistent cervical cancer screening programs, the HPV vaccine offers the best option to reduce the morbidity and mortality associated with anogenital and oropharyngeal cancers. Figure 7: Women awaitingmodern liquid-based Pap testing by CerviCusco in the Andes Mountains of Peru (photo courtesy of CerviCusco, Peru). Numerous optical diagnostic techniques have been developed in the last two decades for the detection of epithelial cancers, such as those in the oropharynx and anogenital regions.
Reflectance imaging, such as confocal microscopy and spectral imaging has found applications in oral, cervical and anal cancer screening and detection. Figure 8: Illustration of the principle of diffuse reflectance spectroscopy with a fiber optic probe and the spectrum analysis procedures [100]. More importantly, most VIS–DRS systems use thermal light sources, grating spectrographs, and cooled CCD cameras. Fluorescence imaging is a powerful spectro chemical method that has been widely used for imaging of endogenous fluorophores, such as Collagen, FAD and NADH, or contrast agents (or photosensitizers) in biological tissue. In conjunction with targeted molecular probes, it has been shown that fluorescence goggles accurately detect many forms of tumors including breast tumors and liver tumors, in small animal models [143–145]. Studies have been successfully conducted to prove the feasibility of using the fluorescence goggle systems at the point of care [143]. The fluorescence goggle platform has been applied to guiding breast and liver cancer surgeries, which showed the feasibility of using the system to guide oncologic interventions. Smartphones represent one of the most exciting consumer electronics devices that have significantly changed the way people communicate during the past decade. The cost of wireless technology has also decreased over the years, thereby making smartphones a more affordable device. Readily available sensors such as cameras (CMOS⁄CCD), gyros, accelerometers, GPS, magnetic field sensing etc.
Data uploaded to central servers wirelessly can be used to create spatio–temporal maps of various conditions visualized in real time. Most Smartphone–based devices consist of an accessory which could be attached to a smartphone. Almost all of the smartphone–based devices that have been reported so far are realized through the attachment of an external module to smartphones. The main objective for this external module would be to decompose the incoming light into its spectral components.
Many other external modules have also been reported in the literatures but only a few of them have been discussed here for conceptual purposes. Despite many improvements over the last decades, prevention, screening and diagnostic tests of cancers in the oropharynx and anogenital regions remain a huge challenge in developing countries and resource–poor areas.
The high resolution and sensitivity offered by optical diagnostic techniques make them promising solutions to the health problems related to oral, cervical and anal cancers in resource poor settings. Despite of the encouraging progress in the past decade, optical diagnostic techniques for developing countries are still in their nascent research stage.
In the next stage of development, it will be likely that the research community will establish a common calibration standard, which will enhance the quality control and clinical systems.
Larger scale clinical studies to compare sensitivity and specificity of optical techniques with that of the gold standard, such as pathology, are also needed to facilitate the clinical translation of various optical systems. Approximately 30,000 new cases of oral cancer and 7,500 deaths due to oral cancer will occur this year. It is common for women to have annual pap smears or mammograms and for men to have prostate exams.
Our office is making it a mission to increase your awareness of oral cancer and to find oral cancer in its earliest stages.
The infographic above shows a word cloud based on an article about mouth cancer on the PubMed Health website.
Spread: Most oral cancers are squamous cell carcinomas, a type which tends to spread particularly quickly. 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. Of these human papillomavirus (HPV)–induced cancers, there are 528,000 cases of cervical cancer with 274,000 deaths per year (Figure 1a) [1].
In the United States, incidence rates of anal cancer and severe anal precancers have increased twofold since the 1970s [7].
The anal cancer is characterized by an irregular surface contour and the presence of atypical blood vessels.
Essentially ubiquitous, approximately 80% of individuals will become infected with HPV during their lifetime. These prophylactic vaccines will provide tremendous benefit by reducing the mortality and morbidity associated with HPV–induced cervical cancers.
Furthermore, the tests are relatively expensive and may not include all of the identified oncogenic HPV types. Following a one minute application of undiluted vinegar, any resulting transient white epithelium noted on the ectocervix by naked–eye examination is considered abnormal.
The poor test specificity of VIA leads to many normal women, particularly young women with an active transformation zone (appears white with VIA testing), receiving unnecessary treatment. However, compliant and accurate surveillance, along with proper diagnosis and treatment are required for this outcome. The long villous-like projections are a common morphologic appearance of HPV-induced lesions(photo courtesy of Daron Ferris, MD). The opaque white epithelium and coarsely dilated mosaic blood vessels are diagnostic of CIN 3(photo courtesy of Daron Ferris, MD). However, adequate resources for regular screening, appropriate diagnoses, effective treatment and proper follow–up are required. Where implemented on a serial interval basis, cervical cytologic screening using conventional Pap tests has significantly reduced the incidence of cervical cancer [57,58]. However, widespread implementation is required, in addition to a reliable cold–chain transport system. Individual and cultural barriers include lack of a tradition of preventive health seeking behaviors, less exposure to medical procedures, poor knowledge of cervical cancer, language barriers, negative views of health care providers, lack of spousal support for health care, anxiety and fear over potential serious diagnoses and cancer, shortage of female healthcare providers, and modesty over exposing the genital region [69]. These techniques include optical coherence tomography (OCT), reflectance imaging, diffuse reflectance spectroscopy (DRS), fluorescence imaging, and smart phone based diagnostic devices. It uses low–coherence interferometry to produce a 2D image of tissue microstructures in a way that is analogous to ultrasonic imaging. Clark et al., [77] characterized features of normal and neoplastic oral mucosa in 15 biopsy pairs from 17 patients using reflectance confocal microscopy. In DRS, a beam of broadband light emitted from a light source, such as thermal lamp, white LED or laser diodes, is launched into a tissue, often through multimode optical fibers, as illustrated in Figure 8 (upper left). The absorption and scattering properties of epithelial tissues reflect their underlying physiological and morphological properties [117]. Thermal light sources have large footprint, short life–time, low power efficiency, and low coupling efficiency to optical fibers. In fluorescence imaging molecules of the analyte are excited by light at a certain wavelength and emit light of a longer wavelength. Sub–millimeter nodules that are not obvious to unaided eye can be detected by fluorescence goggle.
In the future, the fluorescence goggle technology can be potentially applied to management of cervical, anal and oral cancer, in both developed countries and developing countries.
The number of smartphones has increased tremendously throughout the world in the last 5 years. Thereby, realizing a distributed sensing approach which allows for application of smartphones for disease surveillance and management as well as epidemiologic studies in general.
Such an arrangement allows for the use of different accessories to realize different diagnostic tools on a single cellular device. This is mainly due to the lack of appropriate medical infrastructure, expensive resources and well–trained personnel to support the organized screening and diagnostic programsthat are available in the developed world.
The cost consideration also favors optical techniques, as they can be manufactured with low cost. More coordinated efforts from individual research groups as well as related industries are needed to move these techniques forward. The cost evaluation of optical techniques versus traditional smear test needs to be evaluated.
The changing face of head and neck cancer in the 21st century: the impact of HPV on the epidemiology and pathology of oral cancer. Anal cancer incidence and survival: the surveillance, epidemiology, and end results experience, 1973-2000.
Human papillomavirus genotype distribution in anal cancer in France: the EDiTH V study, Int J Cancer. Human papillomavirus genotypes in anal intraepithelial neoplasia and anal carcinoma as detected in tissue biopsies, Mod Pathol. According to the American Cancer society, the most common reason for this high death rate is that lesions are found too late. These exams have been made possible because of public awareness that catching cancers in the earliest form means a greater survival rate. It uses a safe, high energy light and specialized filter technology to look for any abnormal tissues in the earliest stages.
This was a campaign to encourage doctors and dentists to educate their patients about mouth cancer. To reduce your risk of succumbing to mouth cancer, avoid smoking and reduce your alcohol consumption. 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.
The majority of these cases (approximately 85%) occur in resource–poor countries [1,2]. There are approximately 6,000 new cases of anal cancer diagnosed annually in the US, the majority seen in women.


The epithelium of the precancer is thickened and opaque white (photo courtesy of Daron Ferris, MD). While screening guidelines vary worldwide, generally women between 21 and 65 years of age are screened. Due to the relative lack of sensitivity of the conventional Pap test, annual screening is necessary to detect precancers before developing into cancers. According to American Society for Colposcopy and Cervical Pathology (ASCCP) management guidelines, there are several uses for HPV testing [38]. VIA is also unable to examine the endocervical canal where many neoplasias arise, particularly in postmenopausal women or women using progesterone only contraception. Colposcopy is the diagnostic procedure used following screening tests to evaluate women with potential lower genital tract neoplasias (Figure 4 and 5). Discriminating levels of colposcopic abnormality, and even normal from abnormal colposcopic findings, requires ample clinical experience. Unfortunately, for many women living in developing, resource–poor countries, modern screening methods designed to detect precancerous cervical disease are either not available or not affordable. Yet, the highly complex Pap test system suffers from sampling, laboratory and equipment errors, [59, 60] patient noncompliance, [61] inappropriate interval screening, [62,63] inadequate follow–up of abnormal Pap test results, [64,65] poor sensitivity, [66,67] and the need for multiple (annual) testing and multiple patient visits. Presently, most resource–poor nations are critically challenged by the cost of vaccination and lack of appropriate infrastructure. Other factors include religious beliefs, perceived lack of risk, embarrassment, and other competing priorities (lack of time). Here we briefly review OCT and reflectance imaging, but focus our discussions on DRS, fluorescence imaging, and smart phone based diagnostic devices forthe potential in resource–poor settings.
Carlson et al., [78] used confocal reflectance microscopy on ex vivo cervical biopsies and in vivo cervical tissue to image the morphologic and biochemical changes associated with precancer.
The photons propagating in the tissue may experience various events, including elastic scattering, Raman scattering, absorption and fluorescence. In the visible band, dominant absorbers in oral and cervical tissue are oxygenated (HbO2) and deoxygenated hemoglobin (Hb), arising from blood vessels in the stroma. Contact measurement can also avoid specular reflection from the tissue surface which does do not carry any useful tissue information. Spectrometers using grating spectrographs and cooled CCD cameras have extremely high wavelength resolution and sensitivity, but are very bulky and expensive and consume a large amount of electrical power. Fluorescence imaging features very low detection limits and high molecular sensitivity and specificity. The HRME employs a blue LED as its excitation source, a fiber–optic imaging bundle with 30,000 pixels for tissue illumination and fluorescence collection, and a CCD camera for image detection. Surgeons conventionally rely on pre–operative imaging technologies to guide surgical procedures. Recently, the prototype fluorescence goggle has been translated from the bench top into clinical surgical studies for hepatocellular carcinoma (HCC) [146]. Using the wireless–capable fluorescence goggle, an experienced physician can guide the assessment of cancer from remote sites. Moreover, they are integrated with some key features such as wireless communication, camera, global positioning systems (GPS), gyros, and accelerometers etc., which improve its functionality in an integrated manner.
Based on an UN report, there are currently 6.8 billion smartphones subscribers all over the world. With available photonics technologies, miniature CCDs and spectrometers can now be manufactured and integrated into optical diagnostic systems at low cost, provided that there is enough need.
In addition, the use of optical imaging and spectroscopy will be primarily compatible with assessable organs due to the limitation of light penetration in deeply embedded tissues.
In addition to checking the back of your throat, your gum tissues, feeling under your tongue and making you stick it out at me, we will also be checking for abnormal tissues with the VELSCOPE. Early detection is crucial in combatting this disease so a dental checkup every six months is recommended. 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. Certain populations are at an increased risk for anal cancer including immune suppressed individuals (HIV+, organ transplant or other patients on immunosuppressive pharmacologic agents), patients at behavioral risk (men who have anal sex with men) and women with a history of severe HPV–induced genital precancers or cancer. While the majority of HPV infections regress spontaneously without treatment, particularly in immunecompetent individuals, with continued viral persistence some produce neoplasias. The qHPV vaccine is 100% effective in preventing anogenital neoplasia associated with the four HPV vaccine types when administered to people naive to those HPV types. But despite extensive marketing of the HPV vaccines in the United States and other resource rich countries, vaccination rates remain embarrassingly low. Cancer can be universally prevented when premalignant changes are detected early and treated adequately.
As a consequence, VIA suffers from the inability to determine exam adequacy (identification of the entire squamo columnar junction and transformation zone), discriminate epithelial and vascular changes, appraise positive findings using intense illumination and magnification, and recognize falsely positive diagnoses secondary to the presence of immature metaplasia, repair or inflammation that also assumes a transient aceto white, or in the case of VILI, a yellow color. The colposcope, astereoscopic binocular microscope with a powerful light source, is used to detect cervical neoplasias and to identify abnormal tissue for biopsy [16].The goal of colposcopy is to identify cervical cancer precursors to enable eradication of premalignant lesions in order to preclude their progression to cancer. Determining where to selectively obtain small representative biopsies that reflect the worst disease is a skill only acquired with rigorous training. Consequently, cervical cancer is the number one cause of death from cancer for women in these countries. Moreover, testing is labor intensive, at risk to contamination (PCR processing) and technically too advanced for rural settings. Failure to obtain cervical cancer screening is the major reason for developing cervical cancer (other than failure to clear oncogenic HPV infection once infected). Yet, even in developed countries, this practice does not prevent oral cancer, but only helps in early stage detection. Wang et al., [79] demonstrated a MEMS micromirror enabled handheld confocal imaging probe for portable oral cancer detection with a large field of view. Some of these photons escape from the tissue surface, after multiple elastic scattering, as reflectance. Light scattering is primarily caused by cell nuclei and organelles in the epithelium and stroma, as well as collagen fibers and cross–links in stroma. However, the contact DRS systems have not been specifically designed to be robust and reliable, especially in resource–poor settings. In addition, a stable power supply is very often required to operate a thermal lamp and a CCD camera.
The VIS–DRS channel measures the quantitative information about tissue physiological and morphological properties. A number of studies have investigated the use of fluorescence imaging for screening and detection of cancers in the oropharynx and anogenital regions [118,134–138]. It was claimed that the system can be built in a day using commercial components for under US$5,000. In a preclinical study, the functional status of the tumor are imaged by a veterinarian performing the fluorescenceguided surgical procedures and simultaneously transferred wirelessly to the computer of a remote expert [143]. More importantly, the report claims that the rate of cell phone diffusion into developing countries is at 89% as compared to 96% globally.
The same apparatus can be used for bright field imaging, with the filters and LED removed [157]. The scattered light from the sample plane is filtered by the LP filter, acting as a background rejection mechanism which is necessary to isolate the weak fluorescent signal arising from individual nanoparticles or viruses (on the sample plane).
Smartphone–based spectroscopy has been used to observe the transmission spectra from a finger [149]. Modular design is another effective approach to reduce the system complexity and associated cost. It will also be submitted to your insurance company for payment but at this time some carriers are not covering it.
At Gentle Smiles, we recommend a biannual examination which includes checking for malignant neoplasms such as oral cancer.
The highest incidence rates of cervical cancer are found in Central and South America, Africa and Asia where rates exceed 50 cases per 100,000 women. Although difficult to estimate, there are likely 100 times more cases of anal pre–cancers than anal cancer.
Early adolescents (ages 11–12) who are not yet sexually active represent the ideal target age for vaccination.
Poor qHPV vaccine uptake in the United States (33% for all 3 doses in 2012) has even raised concern from the Centers for Disease Control and Prevention (CDC) [24]. The test involves careful sampling of the uterine cervical or anal transformation zones (squamous ectocervical, columnar endocervical, and interposed metaplastic cells) using one or more cytologic collection devices. However, compliant and accurate surveillance, along with proper diagnosis and treatment are required for this satisfactory outcome. Based on its very high negative predictive value (99%) for excluding significant cervical neoplasias, there is growing confidence in this test. Little equipment or supplies are needed, only vinegar, cotton applicators, a light source and vaginal speculum. Cervical neoplasia exhibits certain morphologic features that can be identified during a colposcopic examination [16].Findings from the colposcopy exam and targeted biopsies determine subsequent patient management. However, colposcopy is somewhat subjective and the quality of practice varies considerably. Liquid–based cervical cytology is more sensitive in detecting cancer precursors than a conventional Pap test. Given a delayed adoption of HPV vaccination worldwide, other novel means of cancer prevention are urgently needed. In fact in the United States, 50% of all cases of cervical cancer are detected in women who never have received adequate screening.
Hence, the high mortality rate of HPV–induced cancers 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 elsewhere.
A detector, often a multimode optical fiber or fiber bundle, collects a portion of the reflectance and relay it to anoptical spectrometer, where the photons are converted to a wavelength–dependent intensity distribution of electrons, termed diffuse reflectance spectrum (upper right). The system complexity also makes it necessary for the operator to have extensive knowledge in optical spectroscopy and professional training on the instrument and probes. The SC channel records a calibration spectrum in concurrent with the collection of a tissue reflectance spectrum. Unlike conventional systems, the near–infrared fluorescence information is imaged in real time and displayed in the wearable eyepieces. In addition to guiding surgical resections, fluorescence goggles can also guide biopsy and staging procedures such as the sentinel lymph node biopsy.
The affordable nature of fluorescence goggles renders them promising candidates for the screening as well as an intraoperative tool in the treatment of oral, cervical and anal cancers in rural areas and developing countries. This suggests smartphone–based diagnosis could potentially reduce healthcare costs, provide access to advanced laboratories through wireless communication to remote parts of the world, and be a fielddeployable means for diagnosis, etc. The low NA imaging system is also reduces the alignment sensitivity to depth of field, such that a coarse mechanical translation stage could be sufficient to focus the cell phone microscope to the sample plane. However, current smartphone–based device accessories lack the integration of a fiberoptic attachment which would provide ease of access to cervical, oral and anal cancer sites.
Portable fluorescence imaging systems is another promising candidate for addressing the current challenges. In fact, turning massively available spare smartphones into diagnostically useful optical imaging or spectroscopy devices has been a hot research topic of the recent Global Health programs at NIH as well as the Bill & Melinda Gates Foundation. Because of the lack of modern prevention practices in these areas, the global mortality rate of cervical cancer is estimated to increase by 25% during the next 10years [2]. Much like cervical cancer, anal cancer is preceded by a pre–malignant condition providing an opportunity for early detection and treatment (Figure 2). More than 100 types of HPV exist with some being oncogenic and others considered nononcogenic. However, the qHPV may be given intramuscularly in 3 doses to both boys and girls ages 9–26. Vaccine uptake is lowest in the southeast United States where the highest rates of cervical cancer mortality are also found.


Recent evidence suggests an urgent need to improve the accuracy of colposcopy [47–55]. The yellow area e with dilated vessels mimics cancer, but merely represents a benign Nabothi an follicle. Yet, because it is considerably more expensive, requires complex laboratory processing and equipment, and may not actually reduce the incidence of cervical cancer in comparison with conventional cytology, its utility in disadvantaged populations is suspect. Despite advances in the prevention of cervical, anal and oral cancer with the introduction of the HPV vaccine and attempts to deliver comprehensive cervical, anal and oral cancer screening programs, women from developing countries continue to experience health disparities for cervical cancer morbidity and mortality.
Epithelial scattering has been shown to increase due to increased nuclear size, increased DNA content, and hyperchromasia [96,117,118,121]. Taken together, it is very difficult for VIS–DRS systems in their current forms to be directly used for cancer screening in resourcelimited settings. By dividing the tissue reflectance spectrum by the SC spectrum, the sources of errors due to light source drift and fiber bending loss can be removed in realtime. Here we focus on two emerging low–cost imaging solutions, a high resolution micro endoscope (HRME) and a fluorescence goggle. For instance, it can guide sentinel lymph node biopsy, a standard cancer staging procedure for many cancer forms [143,144,146].
Based on the data transmitted, the remote expert interacted verbally in real–time with the veterinary surgeon in the lab through a mobile phone to guide the surgery.
They also hold great potential for expanding the current reach of image–guided interventions to currently underserved areas.
This system could be used both for bright field microscopy and fluoroscopy (using fluorescence filters as shown in the figure). Advancements in both smartphones and external modules⁄attachments could provide a more robust device for diagnosis. While the Pap test has substantially reduced the rate of cervical cancer, a preventable disease, too many women continue to suffer even in resource–rich countries. However, screening capabilities or expertise in resource–poor countries are essentially nonexistent.
Based on regional tropism, approximately 40 HPV types infect only the epithelium of the anogenital and oropharyngeal tracts. In addition to excellent efficacy, multiple clinical trials and National Adverse Event surveillance systems (CDC Vaccine Adverse Event Reporting System (VAERS) and CDC Vaccine Safety Data link (VSD)) have demonstrated good qHPV vaccine safety.
While the collection methods are identical, with the former test, cells are transferred directly to a glass slide then quickly fixed at bedside in the exam room. Primary screening with HPV tests is also approximately 25% relatively more sensitive than cytology at detecting neoplasias. Normal native squamous epithelium and mature metaplasia contain glycogen in the superficial and intermediate cell layers. Without other viable solutions, it has been recommended that multiple biopsies be obtained during colposcopy to improve disease detection [56]. Hence, there has been a limited role for cervical cancer screening using a Pap test in resource–poor regions. These health disparities between women from developed and developing countries signal the need for innovative approaches to reduce these disparities and improve the quality of care and health. Reflectance imaging system can potentially be made portable and cost–effective so that it could be used in developing countries [79].
VISDRS have a penetration depth that can be tuned to be comparable to the thickness of the epithelial layer or deeper to probe both the epithelial and stromal layers [109,117,122]. The pressure sensor provides real–time feedback on the probe pressure so that the operator can manually adjust the force applied on it. In the 174 women enrolled in the study, 69 sites appearing abnormal on colposcopy among which 12 showed CIN2+ on pathology.
To achieve fast imaging without motion artifacts, CMOS sensor technology has been applied in fluorescence goggle systems.
The fluorescence goggles are compatible with many forms of contrast agents, including clinically approved indocyanine green and emerging agents such as quantum dots [143–146]. The second slit forms the aperture for the diffraction grating where light is split into its respective components and is captured by the smartphone camera. More women’s life years (death at a younger age) are lost with cervical cancer compared withovarian or breast cancer. Yet, even there, the current HPV vaccines will reduce but not totally eliminate HPV–induced cancers. Using liquid–based testing, after sampling, the cells are instead transferred to a liquid preservative and the slide is later processed in the laboratory. Unfortunately, the positive predictive value of a single HPV test result for predicting the presence of severe cervical neoplasia correctly is no greater than 20%. Iodine has an affinity for glycogen; hence normal epithelium appears mahogany brown following the application. Yet, the collection of multiple randomly obtained biopsies is also fraught with serious problems.
If biopsies were incorrectly obtained from a, b, d or e, the patient would receive no treatment.
Moreover, when adopted in many of these areas, the effectiveness has been disappointingly poor. However, remote image interpretation may be required to achieve an accurate diagnosis due to the lack of experienced imaging specialist in low–resource regions.
Both tissue compositions and morphological information have been identified as useful biomarkers for cancer diagnostics. It is generally believed that the changes may be attributed to the compression of the blood vessels which causes reduced blood flow and alterations in the metabolism of the tissue as well as a change in the density of the scatterers [124–132].
Although less than 15,000 women in the United States develop cervical cancer per year, greater than ten–fold more are afflicted by precancerous conditions causing significant morbidity from additional diagnostic tests, histological sampling and surgical interventions.
Approximately 90% of oropharyngeal cancers are buried in the crypts of the tonsils or located at the base of the tongue [5,6].Both of these sites are difficult to screen clinically due to location and the tendency to elicit an uncomfortable gag reflex in the patient. HPV 16 is the most frequent HPV type detected in cervical (in addition to vaginal and vulvar), oral and anal cancers. Unfortunately, distribution of HPV vaccines to resource–poor regions has suffered from high cost and logistical issues. Both types are Pap stained and then examined microscopically by trained health care providers. In many cases, a positive test may simply indicate acute, subclinical HPV infection (no detectable dysplasia), transmissible HPV from a sexual partner or only a transient condition. Normal immature metaplasia and all neoplasias do not contain glycogen, and therefore appear yellow following iodine application.
Proper colposcopy and cervical biopsy techniques are imperative during the evaluation of women with cervical cytologic abnormalities. However, if c is biopsied, surgery is required to prevent progression to invasive cancer (photo courtesy of Daron Ferris, MD).
Hence, because of the many challenges to HPV–related cancer prevention described, optical diagnostic techniques are necessary and may potentially solve many of the current existing dilemmas encountered in the effort to reduce these preventable cancers. It is therefore critical to measure and control the probe contact pressure in order to obtain reproducible and intact tissue physiological parameters. In contrast with HPV–induced disease located in other parts of the body, oropharyngeal precancer lesions are not visually appreciated. Yet in Japan, 80% are of glandular cell origin which is more difficult to detect by current screening and diagnostic methods. Widespread gender neutral HPV vaccination also critically impacts HPV–related disease. Hence, because of slow vaccine uptake worldwide, a large number of unvaccinated populations are exposed to the risk of other HPV types, traditional screening programs are still essential.
Because the prevalence of HPV is quite high in women 30 years of age or younger, its use is limited primarily to older women. Accurate cervical biopsy is the principal factor that ultimately determines proper diagnosis and management. The device has been tested for characterizing pressure response of oral mucosal tissue in vivo in healthy volunteers. Yet, these secondary cancer prevention strategies are associated with tremendous expense ($8 billion⁄yr.
Consequently, virtually no screening testing is performed for oropharyngeal cancer, particularly in resource–poor regions.
Advanced cases of anal cancer have a high mortality rate depending on the surgical stage and nodal involvement [7]. Cytologic diagnoses are rendered using the Bethesda System terminology as NILM, ASCUS, ASC–H, AGC, LSIL, HSIL, AIS, and cancer.
However, cervical neoplasias identified by random biopsy may not actually represent true cancer precursor lesions that require surgical intervention as small, occult lesions may resolve spontaneously. Clinical validation of the device in a low–resource setting is necessary for identifying contrasts in optical biomarkers that vary with different grades of cervical intraepithelial neoplasia from normal cervical tissues.
Becauseof no screening test, oropharyngeal cancers are usually detected only when a large mass is noted.
The conventional cervical Pap testis approximately 50% sensitive at detecting cervical neoplasia and the liquid–based test is approximately 80% sensitive.
Because no special equipment is necessary, VIA and VILI are considered inexpensive screening tests for cervical cancer.
Further, a random biopsy approach risks histological overcall of normal epithelia (immature metaplasia) that mimic neoplasia. Infection may produce condyloma, precancers or cancer of the cervix, vagina, and vulva in women, penis in men, and oropharynx and anus in both sexes. They have proven somewhat effective at reducing cervical cancer rates in resource–poor countries where no other screening options are available. A few of their designs for externals modules include techniques using rotating optical filter wheels, acoustooptical tunable filter (AOTF), liquid crystal tunable filter (LCTF), and diffraction grating.
Despite various treatment options, the 5–year survival rate is approximately 25% [5,6].
Non–oncogenic HPV causes recurrent respiratory papillomatosis, a debilitating and sometimes lethal upper airway condition characterized by diffuse condyloma that may compromise respiratory function [15]. The sensitivity of the anal Pap test is much lower and the rate of unsatisfactory tests much greater due to limitations of the Dacron swab used for anal Pap testing. The sensitivity of VIA is similar to the Pap test, but unlike the Pap test, it does not require specimen collection or processing. Hence, there may be a role for sophisticated novel technology to assist the identification and assessment of cervical lesions. It is important to note that spectral images could be obtained by using filters such as rotating filter wheels. An oncogenic HPV infection of immature metaplastic epithelium in the cervical or anal transformation zone initiates pathogenesis. Yet, there is substantial variability in the sensitivity of VIA primarily due to experience, training and inherent weaknesses of the test.
With HPV persistence, cervical or anal cancer precursor lesions or cancers may slowly arise [16]. While cervical cancer usually results from the serial progression of CIN1 to CIN2 to CIN3 and then cancer, some oncogenic HPV infections advance directly to CIN3.
However, the overall gradual development of these neoplasias to cancer normally enables routine screening programs to detect disease at early, universally curable stages. Until low cost HPV testing is realized, VIA or VIA with low power magnification (VIAM) combined with cryotherapy may be the most viable option for reducing the mortality associated with cervical cancer in the developing world.



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