Precancerous Phase Research Articles

Screening accuracy of PAP and VIA in terms of Colposcopy guided cervical biopsy: A comparative study

Introduction: Approximately 80% of cervical cancer occurs in developing countries of which India contributes about 20-30% of the global burden. WHO considers cervical cancer as a preventable disease because it can be diagnosed in its precancerous phase. Cytology and VIA for screening and colposcopy for directed biopsy jointly may achieve accuracy of approximately 90% to 99%.Methods: An observational cross sectional comparative study was performed to find accuracy of screening protocols of exfoliative cervical cell cytology and visual inspection under acetic acid in terms of the diagnostic test of Colposcopy guided biopsy on 300 symptomatic women of age 18-60 years over the period of one year.Result: Both PAP and VIA positivity increased with age, increasing parity, gynaecological symptoms. PAP and VIA positive results co related with Colposcopy directed biopsy histopatholgy reports in a statistically significant proportion.Discussion: VIA can screen out a large number of women suspected to have cervical cancer in an easy method done in OPD in naked eye and does not require any meticulous microscopic examination with a high degree of sensitivity and high false positivity but on the other hand PAP was less sensitive but more specific test when both combined with Colposcopy guided biopsy.Conclusion: The associations between distribution of women who were Pap +ve and histology +ve as well as VIA and histo +ve were statistically significant.

Tissue-preserving treatment with non-invasive physical plasma of cervical intraepithelial neoplasia-a prospective controlled clinical trial.

ObjectiveCervical cancer represents the fourth leading cause of cancer among women and is associated with over 311,000 annual deaths worldwide. Timely diagnosis is crucial given the lengthy pre-cancerous phase, which is typified by cervical intraepithelial neoplastic lesions. However, current treatment methods are often tissue-destructive and can be accompanied by severe side effects. To address these concerns, our study introduces a novel, gentle approach for the tissue-preserving treatment of CIN lesions.ResultsWe present findings of a controlled, prospective, single-armed phase IIb clinical trial performed at the Department for Women’s Health, Tübingen, Germany. From September 2017 to March 2022 we assessed 570 participants for study eligibility. Of the screened patients, 63 participants met with CIN1/2 lesions met the inclusion criteria and were treated with non-invasive physical plasma (NIPP). Assessment of treatment efficacy was based on a comprehensive analysis of histological and cytological findings, along with high-risk HPV infection load at 3 and 6 months post-treatment. Comparative analyses were performed retrospectively with data obtained from 287 untreated patients in the control group. Our findings indicate that patients treated with NIPP experienced an 86.2% rate of full remission, along with a 3.4% rate of partial remission of CIN lesions, which compares favorably to the control group’s rates of 40.4% and 4.5%, respectively. Additionally, we observed a twofold reduction in high-risk HPV infections following NIPP treatment. Minor side effects were observed, such as mild pain during treatment and short-term smear bleeding or increased vaginal discharge within 24 h after treatment. Given the experimental nature of NIPP treatment and the availability of established standard treatments, our study was designed as a non-randomized study.ConclusionNIPP treatment offers a highly flexible and easy-to-apply method for treating pre-cancerous CIN1/2 lesions. This non-invasive approach is notable for its tissue-preserving nature, making it a promising alternative to current excisional and ablative treatments. CIN1/2 lesions were employed as preliminary in vivo models for the targeted treatment of CIN3 lesions.Clinical trial registrationhttps://www.clinicaltrials.gov, identifier NCT03218436.

Comprehensive analysis for detecting radiation-specific molecules expressed during radiation-induced rat thyroid carcinogenesis.

ABSTRACTAlthough the association between radiation exposure and thyroid carcinogenesis is epidemiologically evident, ’true’ radiation-induced cancers cannot be identified from biological evidence of radiation-associated cases. To assess the individual risk for thyroid cancer due to radiation exposure, we aimed to identify biomarkers that are specifically altered during thyroid carcinogenesis after irradiation in a time-dependent manner in an animal model. Thyroid glands were obtained from rats (n = 175) at 6–16 months after local X-ray (0.1–4 Gy) irradiation of the neck at 7 weeks of age. The gene expression profile in thyroid glands was comprehensively analyzed using RNA microarray. Subsequently, the expression levels of the genes of interest were verified using droplet digital PCR (ddPCR). The expression level of candidate genes as biomarkers for irradiated thyroid was examined in a randomized, controlled, double-blind validation study (n = 19) using ddPCR. The incidence of thyroid cancer increased in a dose- and time-dependent manner and was 33% at 16 months after irradiation with 4 Gy. The Ki-67 labeling index in non-tumorous thyroid was significantly higher in the exposed group than in the control. Comprehensive analysis identified radiation-dependent alteration in 3329 genes. Among them, ddPCR revealed a stepwise increase in CDKN1A expression from early pre-cancerous phase in irradiated thyroid compared to that in the control. The irradiated thyroids were accurately distinguished (positive predictive value 100%, negative predictive value 69%) using 11.69 as the cut-off value for CDKN1A/β-actin. Thus, CDKN1A expression can be used as a biomarker for irradiated thyroid glands at the pre-cancerous phase.

Thermal Ablation Versus Cryotherapy or Loop Excision to Treat Women Positive for Cervical Precancer on Visual Inspection With Acetic Acid Test: Pilot Phase of a Randomized Controlled Trial

(Abstracted from Lancet Oncol 2020;21:175–184) Cervical cancer has a long and treatable precancerous phase, is easily screened for, and is common enough to justify population-based screening even in low- and middle-income countries (LMICs). The standard treatment in high-income countries is large loop excision of the transformation zone (LLETZ).

Algarve Cervical Cancer Screening Programme

Abstract Issue Cervical Cancer (CC) is the 7th most frequent and the 2nd most common in women. The standardized mortality rate, in Portugal is 2.3/100000 inhabitants and Algarve is the region with highest rate, 4.9/100000. Description Programme started in 2010. Population-based screening programme can reduce incidence, mortality and morbidity with an early diagnosis, preventing aggressive interventions in precancerous phase, improving survival and life quality. Target population, woman age 25-64.are invited to primary test liquid-based cytology (ThinPrep) every 3 years. Health Centres are responsible for select, invite, collect samples and send to Hospital laboratory. For positives, a cervical pathology consultation is required. National Guidelines now indicates DNA testing for human papillomavirus (HPV) as primary screening test, each 5 years, to woman age 25 to 60 and screening program changes will be implemented in 2019 with improved response time and lower cost. Results Since 2010 the target population has increased 12% every 2 years and the adhesion rate increased ≈68% and≈108%. Nevertheless the 3rd cycle has showed 10,8% (17.975) adhesion rate. Most women 16.112 (89.6%) had a negative diagnosis, 503 (2,8%) is ASC-US + (HPV test), and 761(4,2%) had a cervical pathology consultation. From those, 117 (15.4%) had a LSIL, 69 (9,1%) HSIL and 2(0,3%) cancer. Cancer detection rate is 0,1 ‰. Lessons The small adhesion rate particularly by aged women, the users unfriendly Information System and direct screening health units management are some of the issues that requires improvement. Also population literacy, self-sampling vaginal fluid and clinical meetings are some of the options to improve screening program. Key messages Cervical Cancer early diagnosis prevent aggressive interventions in a precancerous phase, improves survival and life quality. Better access and health communication are major points in screening programs.

Colorectal Cancer Screening Programme: Algarve Preliminary data

Abstract Problem The burden of disease for oncological problems is significant in Portugal. Population-based screenings, such as colorectal cancer screening (CCS) with faecal occult blood tests (FIT) is a priority program to reduce the burden of disease and a cost-effectiveness measure. Description problem Algarve CCS started in 2017,to early detect colorectal cancer reducing morbidity and mortality. Screening strategy to detect and remove cancer precursors (adenomas) and early cancer detection with less invasive treatment using a non-invasive stool test was selected. A quantitative faecal immunochemical test for haemoglobin (FIT) with higher sensitivity for adenoma and cancer, specific for human globin with no dietary restriction, with a single sample screening is considered a test with higher participation. Target population all gender from 50 to 75 are invited to participate in the CCS by letter. Screening interval is 2 years and FIT cut-off- 117 (ng Hb/mL). Software was used to manage all CCS. Health units distribute the test and a flyer. All FIT-positive were invited to do a full colonoscopy at University Hospital. Results A preliminary descriptive analysis (2017/2019) was made. After exclusions 25017 of target population participate 34,4%(n = 8594),27.5%(n = 6883) submitted it for analysis, 3.9% (n = 266) had positive FIT and were invited for a full colonoscopy with 57.5% (n = 153)participation rate. Cancer detection was 0.9‰ and adenomas detection rate was 9.9%. FIT positive with colonoscopy 3.9% (n = 6) had carcinoma and 44.4% (n = 68) had adenoma. Lessons Some operational changes were made to improve participants and professionals adherence to CCS. Pathology observed in the positive cases, reinforce the need to implement strategies to increase literacy, raise public awareness, keep the screening test and improve accessibility of health facilities. Key messages The importance of a colorectal cancer early diagnosis prevent aggressive interventions in a precancerous phase. The importance of a colorectal cancer early diagnosis improves survival and population quality of life.

Telling the Truth About Caner is a Challenge

Cancer is our neighbor and is a part of our society. It has been here from the beginning of history and is still present hiding the truth about itself and being untouchable in its malevolent version: the unstoppable growth of abnormal cells attacking the body until it succumbs to the aggression.Removing all malignant cells from the body is a challenge because it is the only real cure of the affected person. But, it can be done only if the disease is detected in precancerous phase, cancer in situ, and invasive cancer in clinical stage 1A. All more advanced cancers, notwithstanding the therapy employed, have a much worse prognosis. Medicine is there only to postpone the ultimate fatal outcome.But, this is the same with life itself. It is the blessing to have it, but the challenge to live it. Cancer is the curse of our life. Therefore we have to fight against any carcinogenic and cancer promoter factor in our environments, to search for cancer indicators via surveys among healthy peoples, to put under control the groups at risk, and to conduct regular screening for detection of early signs of cancer as diligently as it has been done in the case of cervical cancer.In this fight, medicine has made many advantages but the cancer is still present. Only a small fraction, the cervical cancer natural history has been altered due to detection of an early suspect for cancer lesions and their removal. The success was achieved in the US where Pap test has helped American health care providers to reduce its mortality rate for 80% and to reverse the curves of cancer prevalence and mortality from increasing pattern to decreasing.This success was achieved in a group of 50 million women at risk, where 10% were found as suspect, subject to further diagnosis, only 1 million was confirmed as carrying on cancer indicators, and 40,000 lesions removed. Still, due to errors in sampling specimens, diagnostic errors or ineffective therapies, 12,000 joined the prevalence and 4,000 died per annum.Worldwide, this concept failed. The global outreach is below 20% of women at risk, and curves of cervical cancer prevalence and mortality are still on rise. What can be done? It was our humble challenge for more than 30 years of research. Finally, a light started to appear in the tunnel of cervical cancer destiny. It is the change of the strategy from the fight against cervical cancer to the fight to reverse the Cervical Cancer Mortality curve in a definite population and for a definite time. The new strategy needs new tools and services. All of this is described in our book, What Every Women Should Know about Cervical cancer, Second Edition (Springer, 2017)Parts were discussed at FASEB meetings in 2016 and 2017. This is a continuation of publishing the results of our research.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Clastogenic ROS and biophotonics in precancerous diagnosis

Cancer is the leading cause of death worldwide. The application of biophotonics for diagnosing precancerous lesions is a major breakthrough in oncology and is associated with the expression of clastogenic bio-markers, such as reactive oxygen species (ROS), namely, superoxide anion radicals, hydrogen peroxide, hydroxyl radicals, and lipid peroxidation products. These ROS are the major sources of ultra-weak biophotons emission; in addition, biophotons are emitted from other biomolecules, which are not associated with ROS. The precancerous phase is diagnosed on the basis of biophoton emission from biomarkers. The type of biophotons emitted depends on the structure of the clastogenic ROS. ROS-based emission of ultra-weak photons can be detected using charge coupled device (CCD) cameras and photomultiplier tubes. Furthermore, spectroscopic and microscopic analysis can yield more advanced and definite results. The frequency and intensity of biophoton emission associated with each ROS provides information regarding the precancerous phase. Previous have attempted to show an association between precancerous growth and biophoton emission; however, their results were not conclusive. In this review, we have addressed multiple aspects of the molecular environment, especially light- matter interactions, to derive a successful theoretical relationship which may have the ability to diaganose the tumor at precancerous stage and to give the solutions of previous failures. This can be a major quantum leap toward precancerous diagnosis therapy. Biophotonics provides an advanced framework, for easily diagnosing cancer at its preliminary stage. The relationship between biophotons, clastogenic factors, and biochemical reactions in the cellular microenvironment can be understood successfully. The advancement in precancerous diagnosis will improve human health worldwide. The versatility of biophotonics can be used further for novel applications in biology, biochemistry, chemistry and social fields.

Integrated proteo-genomic approach for early diagnosis and prognosis of cancer

Cancer is the leading cause of mortality among men and women worldwide. Despite the availability of numerous diagnostic techniques for various cancers, the overall survival rate remains low and the majority of patients die due to late diagnosis and advanced stage of the disease. Diagnosing and treating cancer at its early stages ideally during the precancerous phase could significantly increase survival rate with the possibility of cure and prolong survival. Cancer is a genetic disease and it is illicitly activated by the acquisition of somatic DNA lesions and aberrations in genome structure and defects in maintenance and repair. These somatic DNA mutations known as driver mutations seem to be the prime cause in initiating tumorigenesis. The advances in genomic technologies have immensely facilitated the understanding of cancer progression and metastasis, and the discovery of novel biomarkers. However, changes in somatic mutational landscape of the oncogenome are translated into aberrantly regulated oncoproteome which drives the cancer initiation. Thus, combination of proteomic and genomic technologies is urgently required to discover biomarkers for early diagnosis. The recent advances in human genome based detection of cancer using advanced genomic technologies like NextGen Sequencing, digital PCR, cfDNA technology have shown promise; for example oncogenic somatic mutation variants, transcriptomic analysis, copy number variant, and methylation data from the Cancer Genome Atlas. Similarly, oncoproteomics has the potential to revolutionize clinical management of the disease, including cancer diagnosis and screening based on new proteomic database which embodies somatic variants and post translational modifications, thus devising proteomic technologies as a complement to histopathology. Further, the use of multiple proteomic and genomic biomarkers rather than a single gene or protein could greatly improve diagnostic accuracy and enhance the predictive power for treatment outcome and may enable adequate monitoring of the response to treatment and could be an important option for personalized medicine. The proteogenomic approach has the promise to identify new biomarkers for radiation therapy (RT) which could reliably predict the tumor radiation resistance and which could also accurately predict normal tissue toxicity, and at the same time radiotherapy effectiveness. In this review we have summarize the recent advances in proteogenomic approaches to develop more sensitive diagnostic and prognostic biomarkers which could be translated into improved clinical care and management of the disease.

Retinoids for preventing the progression of cervical intra-epithelial neoplasia.

Invasive cervical carcinoma is preceded by a precancerous phase, cervical intra-epithelial neoplasia (CIN), which can be detected on cervical smears and confirmed by colposcopy and biopsy. Moderate and severe cases of intra-epithelial neoplasia (CIN2 and CIN3) are treated mainly with surgery to prevent progression to invasive carcinoma. Medical methods of preventing the progression or inducing the regression of CIN are needed. Retinoids are potent modulators of epithelial cell growth and differentiation that may have potential for the treatment of CIN. To ascertain whether retinoids can cause regression or prevent progression of CIN. We searched the Cochrane Gynaecological Cancer Review Group's Specialised Register and Non-Trials Database, the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 3, 2010), and MEDLINE and EMBASE (July 2010).For the 2013 update, the searches were re-run as follows: CENTRAL, Issue 3, 2013; MEDLINE, April, Week 2, 2013; and EMBASE, Week 16, 2013. Randomized controlled trials (RCTs) and non-RCTs of retinoids for treating CIN in women. Two review authors independently assessed trial quality and extracted data from the trials. Adverse effects information was also collected from the trials. Five RCTs comparing the efficacy of four different retinoids were identified. Two studies examined the effects on CIN2 and CIN3 of the retinoids N-(4-hydroxyphenyl)retinamide (fenretinide) and 9-cis-retinoic acid (aliretinoin) given orally. Two examined the effect of all-trans-retinoic acid administered topically to the cervix. The fifth study investigated the use of 13-cis-retinoic acid (isotretinoin) given orally to human immunodeficiency virus (HIV)-positive participants with CIN1 and condyloma.Four studies reported no significant effect of retinoids on the progression to higher grades of CIN, and the fifth did not report data on progression. In all studies retinoids had no significant effect on regression of CIN3. Two studies reported that retinoids were associated with regression of CIN2. One reported a greater complete regression of CIN2 over that seen with placebo, which was of borderline statistical significance (odds ratio (OR) 0.5, 95% confidence interval (CI) 0.25 to 1.02). The other study reported a nonsignificant dose-related trend toward increased rates of complete and partial regression compared with placebo. One study reported significantly worse outcomes in women receiving retinoid (OR for regression 6.00, 95% CI 1.00 to 35.91). In general, the retinoid medications were well tolerated.In the 2010 review and in this update, no new studies were identified for inclusion. The retinoids studied are not effective in causing regression of CIN3 but may have some effect on CIN2. The data on CIN1 are inadequate. Retinoids are not effective in preventing progression of CIN of any grade. At the doses given for the duration of treatment studied, the retinoids were reasonably well tolerated.

Oral Fluorescence Imaging Using 405-nm Excitation, Aiding the Discrimination of Cancers and Precancers by Identifying Changes in Collagen and Elastic Breakdown and Neovascularization in the Underlying Stroma

Optical spectroscopy and imaging devices are being developed and tested for the screening and diagnosis of cancer and precancer in multiple organ sites. The aim of the study reported here is to optimize the capability of an optical imaging device to discriminate precancerous tissue from other lesions by identifying ideal excitation wavelengths. The studies reported here used a prototype of a direct fluorescence imaging device that uses 405-nm illumination to excite tissue. There is ample evidence in the literature that 405 nm can distinguish oral cancers from normal tissue. Higher wavelengths may be necessary to differentiate potential confounding lesions, such as abrasions, burns, viral infections, inflammation, and gingivitis. Imaging at 405 nm could help doctors detect precancerous and cancerous oral lesions. Such imaging could be used by dentists, family practitioners, otorhinolaryngologists, general surgeons, obstetrician gynecologists, and internists, and could greatly increase the number of patients who have lesions detected in the precancerous phase.

Colposcopy and cervical intra-epithelial neoplasia

Cervical cancer is both preventable and curable. It has a long natural history with a prolonged pre-cancerous phase that is easily detectable and treatable. Exfoliative cytology remains the mainstay for screening of pre-cancerous lesions. Assessment of women presenting with abnormal cervical cytology and the selection of those requiring treatment relies mainly on colposcopic impressions of the cervical transformation zone and histological appraisal of directed punch biopsies. There is variation in the assessment of cytology, colposcopy and histology findings, and therefore the ‘final’ diagnosis involves of all three disciplines. The need to maximize clinical resources, achieve quicker and more effective management of patients, limit post-operative complications and preserve reproductive function has led to the popularity of local excisional methods for cervical pre-malignancy. Although the cure rates for all local ablative and excisional methods are more than 90% after one treatment, the excisional methods provide a more reliable histopathological diagnosis and the patient may be treated at the initial visit. Cure rates for correlate principally with the extent of the cervical intra-epithelial neoplasia (CIN). The recognition that persistent infection with oncogenic HPV causes cervical cancer has stimulated the search for preventative vaccines. Those vaccines are now available for use and appear to be safe, well tolerated and highly efficacious in HPV naive women. The national HPV immunization programme with the bivalent vaccine was initiated in the NHS in September 2008.

ER-β expression in large bowel adenomas: Implications in colon carcinogenesis

Background A pivotal role of oestrogen receptor-beta has been suggested in colon carcinogenesis in humans. However, few data are available on oestrogen receptor-beta in colorectal pre-cancerous lesions. Aim In the present study, we evaluated oestrogen receptor-beta expression and its possible correlation with proliferative activity and apoptosis in colorectal adenomas and normal colon tissue. Patients/methods Adenomatous tissue from 25 patients with colonic polyps, and normal tissue from 25 controls were used. Oestrogen receptor-beta expression, colonocyte proliferation (expressed as PCNA positivity) and apoptosis were evaluated. Results In adenomatous tissue, a significant reduction of oestrogen receptor-beta was observed compared to normal mucosa (10.1 ± 5.5% vs. 44.2 ± 13.7; p < 0.03), while the expression of oestrogen receptor-alpha remained unvaried. Cell proliferative activity significantly increased in adenomatous tissue compared to normal mucosa (59.3 ± 7.1 vs. 18.5 ± 8.8; p < 0.0001), doubling the PCNA/apoptosis ratio. An inverse correlation was found between oestrogen receptor-beta and PCNA expression in adenomas ( r = −0.81), a datum confirmed by confocal microscopy evaluation. Conclusions Our data demonstrate, for the first time, a significant reduction of oestrogen receptor-beta expression already in the pre-cancerous phase of colon carcinogenesis. This suggests a role of selective oestrogen receptor-beta agonists in the prevention of colorectal cancer.

Colposcopy and cervical intraepithelial neoplasia

Cervical cancer is both preventable and curable. It has a long natural history with a prolonged pre-cancerous phase that is easily detectable and treatable. Exfoliative cervical cytology remains the mainstay for screening of pre-cancerous lesions (cervical intraepithelial neoplasia, CIN). Assessment of women presenting with abnormal cervical cytology and the selection of those requiring treatment relies mainly on colposcopic impressions of the cervical transformation zone and histological appraisal of directed punch biopsies. There is variation in the assessment of cytology, colposcopy and histology findings, and therefore the ‘final’ diagnosis involve of all three disciplines. The need to maximise clinical resources, achieve quicker and more effective management of patients, limit postoperative complications and preserve reproductive function has led to the popularity of local excisional methods for cervical premalignancy. Although the cure rates for all local ablative and excisional methods are more than 90% after one treatment, the excisional methods provide a more reliable histopathological diagnosis and the patient may be treated at the initial visit. Cure rates for CIN correlate principally with the extent of the CIN. More than 95% of cervical cancer cases are associated with oncogenic types of human papillomavirus. Important advances have been made in developing recombinant vaccines to prevent and treat this infection. Clinical trials of preventive and therapeutic vaccines have been reported and the vaccine is now available for use.

Manganese superoxide dismutase activity and incidence of hepatocellular carcinoma in patients with Child–Pugh class A liver cirrhosis: a 7‐year follow‐up study

To evaluate possible modifications in the manganese superoxide dismutase (MnSOD) activity during neoplastic transformation of a cirrhotic liver and to find out whether its assessment may have predictive value to identify cirrhotic patients at a higher risk of hepatocellular carcinoma (HCC). Seventy-one consecutive subjects with Child-Pugh class A liver cirrhosis were recruited. At the time of enrolment, HCC was diagnosed in 20 cirrhotic patients. The 51 cirrhotic patients without HCC were followed up for the occurrence of tumour by 6-monthly screening for 7 years. During follow-up, 16 patients developed HCC. Seventy healthy subjects formed the control group. MnSOD activity was assayed spectrophotometrically. Serum MnSOD activity was significantly lower in 70 healthy subjects compared with 51 cirrhotic patients and 20 cirrhotic patients with HCC. Cirrhotic patients who developed HCC during follow-up showed significantly higher values of MnSOD activity than HCC-free patients. The best cut-off of MnSOD activity was 0.40 U/ml. At this cut-off, chi2 analysis revealed that MnSOD activity was significantly different between the HCC-free cirrhotic patients and cirrhotic patients who developed HCC. The present findings suggest that during neoplastic transformation of cirrhotic liver, an increase in MnSOD activity may occur already during the precancerous phase, making this enzyme a probable malignancy-associated parameter.

Inhibited interpersonal coping style predicts poorer adherence to scheduled clinic visits in human immunodeficiency virus infected women at risk for cervical cancer.

One of the most common gynecologic conditions among HIV+ women is cervical dysplasia, the precancerous phase of cervical cancer. Therefore, adherence to gynecology visits may be among the most important health care practices for HIV+ women. However, no research has evaluated the psychosocial factors associated with health care practices among HIV+ women at risk for cervical cancer. This study examined the relationship between inhibited interpersonal coping style and adherence to primary care and obstetrics/gynecology visits in HIV+ women with Human Papillomavirus (HPV) infection. Twenty-eight HIV-1 seropositive Black, non-Hispanic women underwent a psychosocial interview, blood draw, and gynecologic examination. The Millon Behavioral Health Inventory was used to assess coping style. Medical chart review was used to assess adherence to scheduled special immunology clinic visits for 24 months following study entry. Results suggested that greater inhibited coping style significantly predicted greater nonadherence to clinic visits during 1-year (beta = .45, p = .04) and 2-year (beta = .58, p = .02) follow-up, even after controlling for the possible confounding effects of recent depressed mood on adherence. Social support satisfaction did not mediate the relationship between inhibited coping style and nonadherence. These findings suggest that interpersonal coping style assessment may be a useful tool in predicting adherence in HIV+ women with HPV. Future research should assess the effect of psychosocial interventions on coping style, adherence, and cervical dysplasia in HIV+ women with HPV.

Relative Risks for Squamous Intraepithelial Lesions Detected by the Papanicolaou Test among Air Force and Army Beneficiaries of the Military Health Care System

Squamous cell carcinoma of the uterine cervix typically has a curable precancerous phase of 5 to 10 years, during which the Papanicolaou (Pap) test can often detect characteristic cytologic features. The records of 126,024 Pap tests from January 1994 through June 1999 were reviewed. The distribution of cervical dysplasia was unequally distributed between age and military relationship groups, with younger women and active duty women being at increased relative risk for squamous intraepithelial lesions.

Intraepithelial neoplasia, wart virus and colposcopy

Cervical cancer is both preventable and curable. The disease has a long natural history with a prolonged precancerous phase, which is easily detectable and treatable. The Pap smear remains the mainstay for screening of precancerous lesions, cervical intraepithelial neoplasia (CIN). Assessment of women presenting with abnormal cervical cytology and the selection of those requiring treatment relies mainly on colposcopic impression of the cervical transformation zone and histological appraisal of a directed punch biopsy. Colposcopy remains a subjective technique requiring extensive training and experience. There is high interobserver variability that affects, amongst other factors, the adequacy of directed punch biopsies.Although the grade of CIN correlates with the size of the lesion, CIN III may occur as a small focus and CIN I may be extensive. Cure rates for CIN correlate principally with geographical extent. It has been shown that small lesions similarly have high cure rates regardless of histological grade.Management of cervical precancerous lesions has changed significantly over the last few years. The need to maximise the clinical resources, quicker and more effective management of patients, limit postoperative complications and preserve reproductive function has led to the popularity of local excisional methods. Although the cure rates for all local ablative and excisional methods is in excess of 90% after one treatment, the excisional methods provides a more reliable histopathological diagnosis and the patient may be treated at the first visit—the ‘see and treat’ approach.It is now established that 95% of cervical cancer cases are associated with oncogenic types of human papilloma virus. Important advances have recently been made to develop recombinant vaccines to prevent and treat this infection. Clinical trials on preventive and therapeutic vaccines are underway. The vital question however prevails as to what will come first—an effective screening tool or a preventive vaccine?

Screening for colorectal cancer

Colorectal cancer is the second leading cause of cancer death in the U.S. and common throughout the world. The biologic behavior of this cancer suggests that it can be prevented: most cancer arise from adenomas, which progress over many 'years from small «5mm) lesions to cancer and can be identified during a precancerous phase. Now there is strong evidence that screening prevents incidence and mortality form colorectal cancer but disagreement about the best strategy. Four screening methods are available. They differ is the strengthy: of evidence supporting them, cost and acceptability. I) The strongest evidence is for testing for fecal occult blood (FOBT): a guaiac-based test on 2 specimens from 3 consecutive stools yearly, with colonoscopy for patients with positive tests. A randomized controlled trial of this strategy showed a reduct on in mortality of one third and others now in progress are showing comparable results. This method aims mainly at early detection of cancer, not polyps, because polyps infrequently bleed. 2) Sigmoidoscopy has been shown to reduce mortality from colorectal cancer by two thirds in the segment of the colon examined but the evidence, from two case control studies, is not as strong as with randomized trials and only about half of the colon is examined. 3) Finding romoving polyps, by colonoscopy, seems to prevent colorectal cancers from arising. Winawer and colleagues have shown that patients who have had their colon cleared of polyps and remain under surveillance with colonoscopy every 1-3 years have an incidence of cancer of only about 20 percent of similar patients, in other cohOlts. 4) Finally, double contrast barium enemas detect large (high-risk) polyps and early cancers about as well as colonoscopy and are less expensive and more acceptable. However, there is no direct evidence that screening with barium enemas prevents cancer incidence or mortality and evidence that barium enema and colonoscopy have comparable sensitivity and specificity is not strong. Screening usually begins at age 50 years: about 90% of cancers occur after that age. Patients are reluctant to submit stools or undergo endoscopies but their compliance can be improved. The monetary cost of screening for colorectal cancer appears comparable to screening for other common cancers such as breast. The false positive rate is high; as many as 40 positive FOBT tests must be worked up for every cancer found. Some patients are known, from history and phisical examination, to be at increased risk, for their age, for colorectal cancer. The main risk factors are specific syndromes (familial adenomatous polyposis, hereditary non-polyposis colon cancer, inflammatory bowel disease) and a family history of colon cancer, especially first degree relatives with onset before age 45 years. There is consensus that patients with these conditions should be screened differently (earlier onset oftesting, at shorter intervals and with more powerful testing such as colonoscopy rather than FOBT) but no strong evidence favoring any of these strategies. Genes for the inherited syndromes have been identified and can be used to predict risk within affected kindreds but are not presently useful for general screening. Most current recommendations include yearly FOBT with or without sigmoidoscopy every 5 years, both after age 50 years, with colonoscopy for patients with positive tests. However, new forms of testing and evidence of effectiveness for existing methods are accumulating rapidly and these recommendations are likely to change.

Gamma glutamyl transferase activity in rat colon during experimental colonic carcinogenesis.

Colonic gamma glutamyl transferase activity is raised in colonic malignancy. This study was undertaken to determine how early and how extensively this raised activity occurs during carcinogenesis. Sixty rats were given weekly injections of dimethylhydrazine for 16 weeks, and 20 rats acted as controls. Groups of treated and control rats were sacrificed at regular intervals during the pre-cancerous phase of carcinogenesis, and gamma glutamyl transferase activity was measured at several sites in the colon. Gamma glutamyl transferase activity was raised as early as 4 weeks after the first injection of dimethylhydrazine (p less than 0.05), and the elevation persisted until the development of overt tumours. The raised gamma glutamyl transferase activity was observed throughout both the proximal and distal colon long before the appearance of macroscopic tumours. We conclude that an early and widespread elevation of colonic gamma glutamyl transferase activity occurs during carcinogenesis. This may have useful applications in the early detection of colonic malignancy.