Cervical Cancer
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Cervical cancer is a common type of malignancy accounting for about 6% of all cancers found in women. It is a disease in which cancerous cells develop in the uterine cervix (this is the connecting passage between the uterus and vagina). The human papillomaviruses (HPV) are the principal cause of most cervical cancers. The peak incidence of cervical cancer occurs between the ages of 40 to 55. It is rare before the age of 35, however the incidence of cervical cancer in younger women rose dramatically during the two decades after 1960. Regular Pap smear tests may detect abnormal changes in the cervical tissues, before cancer develops. Symptoms of cervical cancer may include vaginal bleeding after intercourse or bleeding between periods. However, in the early stages of the disease there are often no obvious signs or symptoms, so regular smear tests are important.

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Information for Patients and the Public
Information for Health Professionals / Researchers
Latest Research Publications
Human Papillomavirus (HPV), Vaccination, and Cervical Cancer
Cervical Cancer Screening (including the PAP smear test)
Gynacological Cancers

Information Patients and the Public (22 links)

Information for Health Professionals / Researchers (12 links)

Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Randolph ML, Wu HH, Crabtree WN
Reprocessing unsatisfactory ThinPrep papanicolaou tests using a modified SurePath preparation technique.
Cancer Cytopathol. 2014; 122(5):343-8 [PubMed] Related Publications
BACKGROUND: The frequency of unsatisfactory gynecologic specimens has increased in the study laboratory over the last few years due to the advent of personal lubricants. Similarly, lysed blood, protein, and necrotic debris present a challenge in terms of negative cell transference caused by a clogged filter. In the current study, the authors evaluated the potential use of a modified SurePath reprocessing technique to decrease the frequency of unsatisfactory specimens.
METHODS: An aliquot for human papillomavirus testing was set aside and the remaining specimen in the ThinPrep vial was submitted for sedimentation. A methanol wash was performed using preservative that was added to the remaining sediment. The specimen was vortexed and a protein wash of Tris-buffered deionized water was added before processing. The specimens were stained using the ThinPrep staining protocol. Both the original specimen and the reprocessed specimens were manually reviewed by 1 cytotechnologist and 2 pathologists to determine specimen adequacy.
RESULTS: A total of 1937 ThinPrep Papanicolaou tests were reprocessed and examined. Of these, 1093 (56%) specimens were satisfactory, 624 of which (57%) demonstrated evidence of a transformation zone component. Epithelial cell abnormalities were identified in 116 specimens (10.6%), including 11 high-grade squamous intraepithelial lesion specimens (1.0%); 5 specimens with a classification of atypical squamous cells, cannot rule out a high-grade lesion (0.5%); 21 low-grade squamous intraepithelial lesion specimens (1.9%); and 79 specimens classified as atypical squamous cells of undetermined significance (7.2%).
CONCLUSIONS: The modified SurePath processing technique was adept at handling nearly all of the challenges that biological and environmental conditions (blood, protein, lubricant, etc) present in liquid-based filter preparations. A total of 1093 (56%) of 1937 unsatisfactory ThinPrep Papanicolaou tests were converted to a satisfactory state, resulting in 116 abnormalities (10.6%) being diagnosed that otherwise would have gone undetected

Nair JJ, Rárová L, Strnad M, et al.
Crinane alkaloids of the amaryllidaceae with cytotoxic effects in human cervical adenocarcinoma (HeLa) cells.
Nat Prod Commun. 2014; 9(4):461-6 [PubMed] Related Publications
The family Amaryllidaceae has a long history of usage in the traditional medicinal practices of the indigenous peoples of South Africa, with three of its species known to be used for cancer treatment. Furthermore, the Amaryllidaceae is widely recognized for its unique alkaloid constituents, several of which exhibit potent and selective cytotoxic activities. In this study, several crinane alkaloids derived from local Amaryllidaceae species were examined for cytotoxic effects against the human cervical adenocarcinoma cell line, of which distichamine was the most potent (IC50 2.2 microM).

Corcoran J, Crowley M
Latinas' attitudes about cervical cancer prevention: a meta-synthesis.
J Cult Divers. 2014; 21(1):15-21 [PubMed] Related Publications
Latina women are almost twice as likely to die from cervical cancer as Caucasian women. In response to this disparity, qualitative study has been devoted to this topic. In order to generalize knowledge, insights gleaned through qualitative research methodology may be integrated through meta-synthesis, a methodology that has developed in nursing and related health sciences. The primary purpose of this meta-synthesis was to obtain information about Latinas' knowledge, attitudes, and perceptions regarding cervical cancer and its screening. After applying inclusion criteria, nine studies were located. Results were organized around four areas of inquiry that cross-cut primary studies: 1) Latina participants' knowledge of cervical cancer and its prevention; 2) barriers for regular cervical cancer screening; 3) facilitators that encouraged such screening; and 4) recommendations on how to provide screening for Latina women. Findings indicated that culturally appropriate education and improving accessibility to health care were the most important overall themes for future efforts to improve screening rates among Latinas in the United States.

Related: USA

Steenbergen RD, Snijders PJ, Heideman DA, Meijer CJ
Clinical implications of (epi)genetic changes in HPV-induced cervical precancerous lesions.
Nat Rev Cancer. 2014; 14(6):395-405 [PubMed] Related Publications
Infection of cervical epithelium with high-risk human papilloma virus (hrHPV) might result in productive or transforming cervical intraepithelial neoplasia (CIN) lesions, the morphology of which can overlap. In transforming CIN lesions, aberrations in host cell genes accumulate over time, which is necessary for the ultimate progression to cancer. On the basis of (epi)genetic changes, early and advanced transforming CIN lesions can be distinguished. This paves the way for new molecular tools for cervical screening, diagnosis and management of cervical cancer precursor lesions.

Wongsena M, Suebsamran P, Panomket P, et al.
Prognostic factors of human papillomavirus genotypes of invasive cervical carcinoma: an analytical cross-sectional study in lower north-east Thailand.
J Med Assoc Thai. 2014; 97 Suppl 4:S12-9 [PubMed] Related Publications
BACKGROUND: Cervical cancer (CXCA) caused by persistent infections by high-risk human papillomavirus (HR-HPV) can lead to multi-step carcinogenesis. The best management strategy and significant prognosis for cervical cancer patients remain unclear.
OBJECTIVE: To investigate the associations of the two most common HR-HPVs with clinical outcomes of progression and recurrence status as well as prognosis outcomes of patients.
MATERIAL AND METHOD: An analytical cross-sectional study of patients registered at Ubon Ratchathani Cancer Hospital was conducted from 2007 to 2010. Clinical data, histopathological features, and clinical outcomes of progression and recurrence status were recorded. HPV type-specific E6/E7 nested multiplex polymerase chain reaction (NMPCR) was performed to identify HR-HPV16 and 18 using extracted deoxyribonucleic acid (DNA) from embedded paraffin. Clinical findings and HPV genotypes were analyzed using Fisher's exact test. Association studies of crucial factors and HR-HPV genotypes were performed using logistic regression analysis (odds ratio [OR]) and 95% confidence interval [CI]). A p-value of less than 0.05 was considered statistically significant.
RESULTS: The study found single HPV16 infection in 57.3%, single HPV18 in 17.3%, mixed HR-HPV16/18 in 13.1%, and non-HPV16, 18, or 16/18 in 12.3%. The findings showed significant association among their genotypes and histopathological types and grading (p < 0.0001 and p = 0.014). Clinical outcomes of progression and recurrence status with increased severity of clinical staging were associated significantly (p = 0.001 and p = 0.002). HPV18 type-specific was shown as a poor prognostic type with its relevance to the severity of disease higher than that of HPV16.
CONCLUSION AND DISCUSSION: HPV16 and 18 remain the major type-specifics especially in relation to invasive CXCA, requiring further therapeutic vaccination study and proper prognosis. HR-HPV type-specific is very important during cervical carcinogenesis but other crucial contributing factors for prognostic outcomes should be further elucidated.

Related: Thailand

Geng F, Xing JZ, Chen J, et al.
Pegylated glucose gold nanoparticles for improved in-vivo bio-distribution and enhanced radiotherapy on cervical cancer.
J Biomed Nanotechnol. 2014; 10(7):1205-16 [PubMed] Related Publications
Pharmacokinetics and bio-distribution are crucial factors affecting the performance of an intravenous drug. In this study, we explore the combined use of glucose and polyethylene glycol (PEG) ligands to further improve gold nanoparticle (GNP) pharmacokinetics and bio-distribution, with the aim of using the drug for in-vivo radiotherapy. The inclusion of PEG was found to significantly prolong the half-life period, where PEG-Glu-GNPs achieved 6.17 +/- 3.71 h, compared to 1.23 +/- 0.14 h for Glu-GNPs and 1.07 +/- 0.22 h for uncoated GNPs. Our data indicates that nanoparticle size impacts cell uptake performance, with 20 nm being the optimal diameter for cancer treatment applications. Although PEG-Glu-GNPs mainly distributed in the spleen, liver, lung, and kidneys, the concentration of PEG-Glu-GNPs in tumour tissue was 20 times higher than healthy cells in the uterus and ovaries, reaching 9.22 +/- 2.41 microg/g cancer tissue at 48 h after injection. This difference in uptake holds promise for selective tumor targeting which can in turn lead to more effective radiotherapy through the interaction of X-rays and GNPs. Specifically tumor size after 47 days of treatment had reduced to (769 +/- 92) mm3 compared to (1432 +/- 269) mm3 using X-rays alone and (3514 +/- 1818) mm3 without any treatment. Moreover, the mice remained healthy without statistically significant weight loss. Results of our pharmacokinetic and bio-distribution study as well as therapeutic data for PEG-Glu-GNPs in our tumor bearing animal model demonstrate that PEG-Glu-GNPs provide excellent in-vivo stability, tumor targeting function, and radiotherapeutic enhancement effects, providing useful insights for further clinical studies.

Ward KK, Roncancio AM, Cano MA, Plaxe SC
An ecological analysis of the incidence of invasive squamous cell carcinoma of the cervix in Hispanic women in the United States.
Ethn Dis. 2014; 24(2):243-7 [PubMed] Related Publications
PURPOSE: To evaluate the relationship between county-level characteristics and the incidence of invasive squamous cell carcinoma of the cervix among Hispanic women.
METHODS: The Surveillance, Epidemiology and End Results (SEER) Program's 18 registries from 2000-2009 were queried. Average annual age-adjusted incidence rates for invasive squamous cell carcinoma of the cervix among Hispanic women were calculated. Patients were then stratified by residence in a county with high vs low percent language isolation (LI), income, and education levels.
RESULTS: Among Hispanic women living in high LI, the highest incidence of cervical cancer was found among women residing in counties with low incomes and low education levels (11.3; CI: 10.8-11.8).
CONCLUSIONS: County-level characteristics are associated with cervical cancer incidence in Hispanic women. A more precise understanding of contributing socioeconomic factors such as language may facilitate the design of targeted research studies and interventions, and community-level public policy interventions might be effective in reducing the unequal burden of cervical cancer in Hispanic women in the United States.

Related: USA

Leser KA, Francis SA
Mother-child communication about sexual health, HPV and cervical cancer among antenatal clinic attendees in Johannesburg, South Africa.
Afr J Reprod Health. 2014; 18(1):123-6 [PubMed] Related Publications
Parent-child communication about sexual health is considered an effective strategy for encouraging safe sexual practices among youth. This study used a brief survey to examine mother-child communication among 86 antenatal clinic attendees in Johannesburg, South Africa. Eighty-five percent of mothers reported having enough information to discuss HIV/AIDS prevention with their children, while only 36% reported having enough information to discuss HPV/cervical cancer prevention. Thirty-seven percent of mothers who reported being comfortable discussing HIV/sexual health with their child actually discussed these topics with their child; while 58% of mothers who reported being comfortable did not discuss HIV/sexual health with their child. Future research and program planning efforts should focus on identifying the best strategies to educate South African mothers on HPV and cervical cancer, so that mothers can effectively communicate their knowledge about these topics to their children.

Mojahed S, Karimi Zarchi M, Bokaie M, Salimi T
Attitude and knowledge of Iranian female nurses about human papilomavirus infection and cervical cancer: a cross sectional survey.
J Prev Med Hyg. 2013; 54(3):187-90 [PubMed] Related Publications
BACKGROUND AND AIM: Human Papilomavirus (HPV) is one of the most widespread sexually transmitted diseases is highly related to cervical cancer in women. Cervical cancer's crude incidence rate in Iran is 6-8 per 100,000. The HPV vaccine provides a chance to considerably decrease the transmission of most types of HPV. The aim of this study was to evaluate awareness and knowledge of HPV infection and vaccines and to assess the attitude and approach toward these vaccines among female nurses at Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
MATERIALS AND METHODS: This cross-sectional, descriptive study was performed among 380 female nurses. Data were collected using a questionnaire was consisted in demographic variables and questions on knowledge of participants about HPV infection, HPV vaccine and cervical cancer and also questions on attitude of ourses towards HPV vaccination. The validity and internal consistency of questionnaire was confirmed during experts consents and pilot testing (alpha = 0.79). Data analysis was performed using SPSS15 using chi2-test or Fisher's exact test.
RESULTS: Three hundred and eighty questionnaires were distributed and 357 female nurses completed and returned their questionnaires: Only one hundred and thirty-one of the nurses (36.7%) knew about HPV infection and how it can cause abnormal pap Smear results. about 147 (41.2%) of the nurses stated they would want to be vaccinated. About 146 (40.9%) of respondents supported vaccination of preadolescent girls.
CONCLUSION: The results of this study confirm the lack of knowledge about HPV vaccine and its relation to cervical cancer and also the ways of this cancer prevention. Our study shows an urgent need to design similar studies in other regions of Iran and draw a broad estimation on knowledge of different target groups to make a national program to increase the knowledge of women on this matter and help to decrease the rate of cervical cancer in Iranian population.

Hajializadeh K, Ahadi H, Jomehri F, Rahgozar M
Psychosocial predictors of barriers to cervical cancer screening among Iranian women: the role of attachment style and social demographic factors.
J Prev Med Hyg. 2013; 54(4):218-22 [PubMed] Related Publications
OBJECTIVES: Despite advances in screening and treatment during past several Decades, cervical cancer remains a major health problem for Iranian women. Recent researches have focused on factors related to development of health behavior in an effort to design effective early interventions. The current study aimed to investigate the role of attachment styles on cervix cancer screening barriers among women of Bandar Abbas-Iran.
METHODS: In an analytic-cross sectional study, 681 women aged 21-65 referring to health centers were selected randomly and after completing written informed consents were investigated by Revised Adult Attachment Scale (RAAS) (Collins and Read), Pap smear screening barriers and demographic data questionnaire. The data were analyzed by Pearson correlation coefficient, linear regressions and chi-square test.
RESULTS: The results showed significant association between attachment styles and screening barriers. There was a negative significant relation between secure attachment style and screening barriers and there was a positive significant association between insecure attachment style (anxiety and avoidant) and screening barriers. The regression analysis indicated that insecure attachment style (avoidant) were predictors of barriers to the Pap smear screening test in this regard. There was a significant association between age and residential area and participation in Pap smear test.
CONCLUSIONS: Insecure attachment style is associated with hazardous risk behaviors and these results can be useful for health service providers in preventive planning of screening and identification of people susceptible to risk and the design of the intervention.

Related: Cancer Screening and Early Detection

Hou MM, Liu X, Wheler J, et al.
Outcomes of patients with metastatic cervical cancer in a phase I clinical trials program.
Anticancer Res. 2014; 34(5):2349-55 [PubMed] Related Publications
BACKGROUND: We evaluated clinical outcomes of patients with metastatic cervical cancer referred to a Phase I Clinical Trials Program.
PATIENTS AND METHODS: We reviewed the electronic medical records of 54 consecutive phase I patients with metastatic cervical cancer over 6.5 years and analyzed the correlation between clinical outcome and potential predictors.
RESULTS: All patients had received at least one systemic therapy for metastatic disease before referral. Only two patients declined phase I trial therapy. The median progression-free (PFS) and overall (OS) survivals were 3.6 and 10.6 months, respectively. Patients harboring phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutations or phosphatase and tensin homolog loss, and those with more than two sites of metastasis who received more than one prior systemic chemotherapy before the referral had median PFS of 6.7 and 1.8 months, and median OS of 12.6 and 2.9 months, respectively.
CONCLUSION: Patients with more than two metastatic sites who had received more than one prior system therapy had dismal outcomes. An aberrant PI3K pathway was frequently identified and associated with favorable outcome, providing a promising target.

Song MJ, Lee CW, Yoon JH, Hur SY
Transection of the obturator nerve by an electrosurgical instrument and its immediate repair during laparoscopic pelvic lymphadenectomy: a case report.
Eur J Gynaecol Oncol. 2014; 35(2):167-9 [PubMed] Related Publications
Obturator nerve injury seldom occurs in gynecologic surgery. However, gynecologic oncologic surgery, including pelvic lymph node dissection, increases the risk of this type of injury. Microsurgical techniques are usually performed for the repair of the nerve injury. Herein the authors report a case of obturator nerve injury caused by an electrosurgical instrument during laparoscopic pelvic lymphadenectomy, and its prompt repair by laparoscopic procedure in a 44-year-old patient with cervical cancer.

Mani E, Medina LA, Isaac-Olivé K, Dueñas-González A
Radiosensitization of cervical cancer cells with epigenetic drugs hydralazine and valproate.
Eur J Gynaecol Oncol. 2014; 35(2):140-2 [PubMed] Related Publications
PURPOSE: To evaluate the radiosensitizing effects of the DNA methylation inhibitor hydralazine in combination with valproic acid, a histone deacetylase inhibitor in cervical cancer cells.
MATERIALS AND METHODS: Cell viability assays were performed in the SiHa cervical cancer cell line treated with hydralazine and valproic acid for five days with and without cisplatin. Cell irradiation was performed using teletherapy (1.25 MV).
RESULTS: Neither hydralazine, valproic acid or cisplatin as single agents increased the cytotoxicity from radiation, however, the combination of hydralazine with valproic acid at ten microM and one mM, respectively, did induce radiosensitization (p = 0.046). Interestingly, this effect was further increased with the triple combination of hydralazine, valproic acid, and cisplatin (p = 0.041), where cell viability decreased more than 50% as compared to radiation alone.
CONCLUSIONS: The present results demonstrate that epigenetic drugs increase the efficacy of cisplatin chemoradiation in cervical cancer cells.

Bandera L, La Face B, Antonioli C, et al.
Survival and toxicity of radical radiotherapy (with or without brachytherapy) for FIGO stage I and II cervical cancer: a mono-institutional analysis.
Eur J Gynaecol Oncol. 2014; 35(2):121-7 [PubMed] Related Publications
PURPOSE OF INVESTIGATION: To add to the existing outcome data regarding radical radiotherapy (RT) for FIGO Stage I and II cervical cancer in a mono-institutional series and to evaluate the cost-benefit ratio of the addition of brachytherapy (BRA) to external-beam radiotherapy (EBRT).
MATERIALS AND METHODS: The authors report on 240 patients (pts) with FIGO Stage I and II cervical cancer, consecutively treated with radical RT from 1990 through 2009 at the Istituto del Radio "O. Alberti" (EBRT alone, 32, EBRT and BRA, 189, BRA alone, 19). BRA was delivered with low dose rate (LDR, 133.64%) until 2003 and then with high dose rate (HDR, 75.36%). RT was associated with concomitant chemotherapy (CHT), mainly weekly cisplatin 40 mg/m2, in 87 pts, mostly after 2000. The Chi-square test was used to compare the different variables, the Log-Rank test to compare the actuarial survival values, and the Cox-model for the multivariate analysis.
RESULTS: Five-year actuarial overall survival (OS) equalled 65%, disease specific survival (DSS) 77%. Regardless of disease stage, better DSS was evident in pts treated with EBRT and BRA compared with those treated with EBRT alone (82% and 58% respectively, p = 0.005); pts treated with concomitant CHT (dose intensity > or = 50%) and higher RT doses (RT cumulative EQD2 > or = 75 Gy) obtained better DSS. Complete response (CR) rate approached 88.4% (206/233 evaluable pts) and more than half of the subsequent failures (21/36) were in distant sites. Older patients and those given BRA had better OS and DSS, while BRA dose rate did not result related with these outcomes. Chronic G3/G4 toxicity involved more frequently the intestinal/rectal tract than other organs at risk. Rectal and vaginal serious chronic sequelae developed mainly in pts treated with EBRT and BRA and suggest the need for more advanced treatment techniques.
CONCLUSIONS: the present mono-institutional analysis confirms the efficacy of radical RT for the treatment of cervical cancer and provides support to the role of BRA to obtain better outcomes. An effort to reduce long-term toxicity of the treatment is needed.

Related: Brachytherapy

Tjalma WA, Depuydt CE
Cervical atypical glandular cells and false negative HPV testing: a dramatic reality of the wrong test at the right place.
Eur J Gynaecol Oncol. 2014; 35(2):117-20 [PubMed] Related Publications
BACKGROUND: Due to cervical cancer screening the number of squamous cancer have declined. The number of adenocarcinomas (ADCs) does appear to be rising. ADCs are often missed and human papillomavirus (HPV) testing could be helpful in detecting these abnormalities earlier.
CASE: A 36-year-old woman, who had a normal smear three years earlier, had a pap smear with atypical glandular cells. The L1 HPV test showed that there was no HPV infection. Other HPV tests which looked at E6 and E7 showed an infection with HPV 16. Due to unknown reasons, no action was taken regarding the atypical glandular cells. Two years later the patient was diagnosed with a FIGO Stage IVb ADC of the cervix. The L1 HPV test was still negative and the E6/E7 HPV test was still positive. Despite several multiple treatment modalities she succumbed of her disease two years later leaving behind a young family.
CONCLUSION: HPV test looking only at L1 can give false negative results if the virus is integrated in the human genome.

Watson M, Benard V, Thomas C, et al.
Cervical cancer incidence and mortality among American Indian and Alaska Native women, 1999-2009.
Am J Public Health. 2014; 104 Suppl 3:S415-22 [PubMed] Free Access to Full Article Related Publications
OBJECTIVES: We analyzed cervical cancer incidence and mortality data in American Indian and Alaska Native (AI/AN) women compared with women of other races.
METHODS: We improved identification of AI/AN race, cervical cancer incidence, and mortality data using Indian Health Service (IHS) patient records; our analyses focused on residents of IHS Contract Health Service Delivery Area (CHSDA) counties. Age-adjusted incidence and death rates were calculated for AI/AN and White women from 1999 to 2009.
RESULTS: AI/AN women in CHSDA counties had a death rate from cervical cancer of 4.2, which was nearly twice the rate in White women (2.0; rate ratio [RR] = 2.11). AI/AN women also had higher incidence rates of cervical cancer compared with White women (11.0 vs 7.1; RR = 1.55) and were more often diagnosed with later-stage disease (RR = 1.84 for regional stage and RR = 1.74 for distant stage). Death rates decreased for AI/AN women from 1990 to 1993 (-25.8%/year) and remained stable thereafter.
CONCLUSIONS: Although rates decreased over time, AI/AN women had disproportionately higher cervical cancer incidence and mortality. The persistently higher rates among AI/AN women compared with White women require continued improvements in identifying and treating cervical cancer and precancerous lesions.

Related: USA

Frazer IH
Development and implementation of papillomavirus prophylactic vaccines.
J Immunol. 2014; 192(9):4007-11 [PubMed] Related Publications
Translation of basic scientific findings into practical patient outcomes is a significant exercise even when the goal is conceptually straightforward, as in the development of a vaccine for an infectious disease. Recognition of the association of cervical cancer with papillomavirus infection encouraged development of a vaccine to help with prevention of this very common cancer, causing over 250,000 deaths each year worldwide. To introduce a vaccine program, it was however necessary to develop a technology for making viral Ag, demonstrate that systemic immunization could provide mucosal surface protection in the genital tract, develop assays for vaccine potency, and understand enough about the epidemiology and natural history of the infection to plan effective intervention strategies. This process took ∼25 years. The major hurdle, now that effective vaccines are available, is to ensure their deployment in the countries where they are most needed. The development and deployment of human papillomavirus vaccines demonstrate the benefits of collaborative research activity across the globe, and between academia and industry, to translate scientific discoveries into public health benefits.

Asthana S, Chauhan S, Labani S
Breast and cervical cancer risk in India: an update.
Indian J Public Health. 2014 Jan-Mar; 58(1):5-10 [PubMed] Related Publications
BACKGROUND: Breast and cervical cancers are two major cancers among Indian women. Analysis of trends would help in planning and organization of programs for control of these cancers.
OBJECTIVE: The objective of the following study is to compute risk of breast and cervical cancers using updated data from different cancer registries of India and study of its trends.
MATERIALS AND METHODS: Data on incidence rates of breast and cervical cancers were obtained from six major cancer registries of India for the years 1982-2008 and from the recently initiated cancer registries, North Eastern Registries of India with a total of 21 registries. Annual percent change in incidence and risk in terms of one in number of women likely to develop cancer was estimated for both the cancers in various registries.
RESULTS: The annual percentage change in incidence ranged from 0.46 to 2.56 and -1.14 to -3.4 for breast and cervical cancers respectively. Trends were significant for both cancers in the registries of Chennai, Bangalore, Mumbai and Delhi except Barshi and Bhopal. North East region showed decrease in risk for breast and cervical cancers whereas increasing trend was observed in Imphal (West) and for cervical cancer in Silchar.
CONCLUSION: North Eastern region recorded decline in the incidence of breast cancer which is contrary to the observation in other registries, which showed increase in breast cancer and decline in cervical cancer incidences.

Related: Breast Cancer Male Breast Cancer

Kirchheiner K, Nout RA, Tanderup K, et al.
Manifestation pattern of early-late vaginal morbidity after definitive radiation (chemo)therapy and image-guided adaptive brachytherapy for locally advanced cervical cancer: an analysis from the EMBRACE study.
Int J Radiat Oncol Biol Phys. 2014; 89(1):88-95 [PubMed] Related Publications
BACKGROUND AND PURPOSE: Brachytherapy in the treatment of locally advanced cervical cancer has changed substantially because of the introduction of combined intracavitary/interstitial applicators and an adaptive target concept, which is the focus of the prospective, multi-institutional EMBRACE study (www.embracestudy.dk) on image-guided adaptive brachytherapy (IGABT). So far, little has been reported about the development of early to late vaginal morbidity in the frame of IGABT. Therefore, the aim of the present EMBRACE analysis was to evaluate the manifestation pattern of vaginal morbidity during the first 2 years of follow-up.
METHODS AND MATERIALS: In total, 588 patients with a median follow-up time of 15 months and information on vaginal morbidity were included. Morbidity was prospectively assessed at baseline, every 3 months during the first year, and every 6 months in the second year according to the Common Terminology Criteria for Adverse Events, version 3, regarding vaginal stenosis, dryness, mucositis, bleeding, fistula, and other symptoms. Crude incidence rates, actuarial probabilities, and prevalence rates were analyzed.
RESULTS: At 2 years, the actuarial probability of severe vaginal morbidity (grade ≥3) was 3.6%. However, mild and moderate vaginal symptoms were still pronounced (grade ≥1, 89%; grade ≥2, 29%), of which the majority developed within 6 months. Stenosis was most frequently observed, followed by vaginal dryness. Vaginal bleeding and mucositis were mainly mild and infrequently reported.
CONCLUSION: Severe vaginal morbidity within the first 2 years after definitive radiation (chemo)therapy including IGABT with intracavitary/interstitial techniques for locally advanced cervical cancer is limited and is significantly less than has been reported from earlier studies. Thus, the new adaptive target concept seems to be a safe treatment with regard to the vagina being an organ at risk. However, mild to moderate vaginal morbidity is still pronounced with currently applied IGABT, and it needs further attention.

Related: Brachytherapy

Liu H, Yang X, Zhang C, Liu X
Small cell carcinoma of the cervix at 32-week gestation: a case report and review of the literature.
Lab Med. 2014; 45(1):52-5 [PubMed] Related Publications
Small cell carcinoma of the cervix (SCCC) in late pregnancy is extremely rare and often misdiagnosed. We describe a case report of a patient who was diagnosed with SCCC at 32 weeks of gestation. During Cesarean section, a radical hysterectomy was performed; the uterus and cervical stroma were excised, the pelvic lymph node was bilaterally dissected, and the para-aortic lymph node was biopsied. During the surgery, a metastatic mass measuring 3 x 2.5 x 2.5 cm in size was found in the left cervical stroma with enlarged obturator lymph nodes. The patient was subsequently diagnosed with stage IIa cervical cancer. The efficacy of radiotherapy and chemotherapy was poor due to the very late stage of the SCCC and the patient died from metastatic disease. Therefore, we suggest that cervical liquid-based cytology, in combination with immunocytochemical and molecular analyses, should be performed for the early detection of SCCC when abnormal vaginal bleeding is present during pregnancy.

Related: Breast cancer in pregnancy

Sangkittipaiboon S
Long-term outcomes of concurrent chemoradiotherapy with weekly carboplatin in locally-advanced carcinoma of the uterine cervix patients.
J Med Assoc Thai. 2014; 97(1):12-9 [PubMed] Related Publications
OBJECTIVE: To study the treatment outcomes of concurrent chemoradiotherapy with weekly carboplatin in locally-advanced carcinoma of the uterine cervix patients and the complications resulting from the treatment.
MATERIAL AND METHOD: Between August 2005 and July 2007, the author identified 105 patients with carcinoma of the uterine cervix. The International Federation of Gynecology and Obstetrics Clinical Stages were IIB, III, and IVA in 83, 19, and three cases, respectively. Mean age was 51.5 years old, ranging from 33 to 79 years. Carboplatin was prescribed weekly concurrent with external irradiation.
RESULTS: The most acute toxicities were in grade 1-2 (grade 3 hematological toxicities were 3.80%). Complete response was achieved in 95 patients (90.5%). Among the 95 responders, 27 experienced recurrences: local recurrences in eight (8.4%), distant failure in 17 (17.9%), and both local and distant failure in two (2.1%). The follow-up time was ranging from three to 96 months (median 76 months). Significant prognostic factors for disease-free survival in multivariate Cox regression analysis were tumor stage and tumor response. With regard to overall survival, multivariate Cox regression analysis confirmed prognostic significance of patients' age, tumor stage, and tumor response. Five-year disease free survival rate was 52.38% (56.63%, 42.11%, and 0% in stage IIB, III, and IVA, respectively) while five-year overall survival rate was 56.19% (61.45%, 42.11%, and 0% in stage IIB, III, and IVA, respectively). Late grade 3-4 gastrointestinal and genitourinary toxicities were 3.2% and 0%, respectively.
CONCLUSION: Concurrent weekly carboplatin and radiation therapy yields high response rate with modest disease-free and overall survivals in locally advanced carcinoma of the uterine cervix. The regimen is feasible with minimal toxicities. Prognostic factors identified in the present study are consistent with other reports.

Related: Carboplatin

Ramdass B, Chowdhari A, Koka P
Cancer-initiating cells as target for prevention of recurring disease etiology: role of these malignant putative progenitor cells in relapse or metastasis of human cervical carcinoma.
J Stem Cells. 2013; 8(3-4):233-51 [PubMed] Related Publications
Evidence suggests that there is a link between high-risk human papillomaviruses (HPVs) and cervical cancer. Studies indicate that persistence of high risk HPVs may determine progression to more severe stages of cervical disease, while the majority of HPV infections are transient and do not seem to be important in cervical carcinogenesis. Earlier studies in different cancers have shown that tumor initiating cells TICs are responsible for tumor formation and progression and interestingly, they are endowed with stem/ progenitor cell properties. In particular, TICs share with stem cells the key feature of self-renewal. The most efficacious therapeutic intervention for cervical cancer is probably vaccination. This review gives an overview on cervical cancer and its potential therapeutic interventions.

Beckenkamp A, Santana DB, Bruno AN, et al.
Ectonucleotidase expression profile and activity in human cervical cancer cell lines.
Biochem Cell Biol. 2014; 92(2):95-104 [PubMed] Related Publications
Cervical cancer is the third most frequent cancer in women worldwide. Adenine nucleotide signaling is modulated by the ectonucleotidases that act in sequence, forming an enzymatic cascade. Considering the relationship between the purinergic signaling and cancer, we studied the E-NTPDases, ecto-5'-nucleotidase, and E-NPPs in human cervical cancer cell lines and keratinocytes. We evaluated the expression profiles of these enzymes using RT-PCR and quantitative real-time PCR analysis. The activities of these enzymes were examined using ATP, ADP, AMP, and p-nitrophenyl-5'-thymidine monophosphate (p-Nph-5'-TMP) as substrate, in a colorimetric assay. The extracellular adenine nucleotide hydrolysis was estimated by HPLC analysis. The hydrolysis of all substrates exhibited a linear pattern and these activities were cation-dependent. An interesting difference in the degradation rate was observed between cervical cancer cell lines SiHa, HeLa, and C33A and normal imortalized keratinocytes, HaCaT cells. The mRNA of ecto-5'-nucleotidase, E-NTPDases 5 and 6 were detectable in all cell lines, and the dominant gene expressed was the Entpd 5 enzyme, in SiHa cell line (HPV16 positive). In accordance with this result, a higher hydrolysis activity for UDP and GDP nucleotides was observed in the supernatant of the SiHa cells. Both normal and cancer cells presented activity and mRNAs of members of the NPP family. Considering that these enzymes exert an important catalytic activity, controlling purinergic nucleotide concentrations in tumors, the presence of ectonucleotidases in cervical cancer cells can be important to regulate the levels of extracellular adenine nucleotides, limiting their effects.

Antić L, Djikanović B, Vuković D, Kaludjerović V
Do women in rural areas of Serbia rarely apply preventive measures against cervical cancer?
Vojnosanit Pregl. 2014; 71(3):277-84 [PubMed] Related Publications
BACKGROUND/AIM: The incidence of cervical cancer in Central Serbia has the higher rate as compared with that in other European countries. Considering mortality rate for cervical cancer, the standardized rate in Serbia is 10.1 per 10,000 females, which is the second highest one after that in Romania with 13.0. The aim of this study was to examine application of preventive measures for cervical cancer in women both from rural and urban areas in Serbia and if they are associated with sociodemographic characteristics and sexual behaviour.
METHODS: We analyzed secondary data of the 2006 National Health Survey of the population of Serbia focused on characteristics of adult females aged 25 to 65 years (5.314 in total) taking into consideration that programme of the organized screening will include female population aged over 25 years.
RESULTS: Respondents from rural areas have gynecological examination less than once a year in comparison with those from urban areas (OR = 0.60, 95% CI 0.54-0.68). Less women from rural areas did Pap test during the last 12 months in comparison with respondents from urban areas (OR = 0.55, 95% Cl 0.48-0.64). Respondents from urban areas less often do the Pap test on doctor's advice in comparison with those from rural one (OR = 0.55, 95% CI 0.42-0.62).
CONCLUSION: This study shows that women in rural areas rarely implement preventive gynecological measures againt cervical cancer in comparison with those in urban areas. Implementation of preventive measures among rural women is conditioned by lower levels of education and lower socioeconomic status.

Mihret W, Yusuf L, Abebe M, et al.
A pilot study on detection and genotyping of humanpapilloma virus isolated from clinically diagnosed Ethiopian women having cervical intraepithelial neoplasia.
Ethiop Med J. 2014; Suppl 1:49-52 [PubMed] Related Publications
BACKGROUND: Human Papilloma virus associated cervical cancers are more prevalent in developing countries compared to developed countries. Cervical cancer is reported as the most frequent malignancy among women visiting hospitals in Ethiopia. This study is a pilot study designed to examine the prevalence and genotypes of HPV in twenty Ethiopian women, clinically diagnosed to have cervical neoplasia, while visiting gynecology unit of a tertiary level referral hospital in Addis Ababa. The objective of this study was to detect the presence of HPV L1 gene and respective genotypes among women clinically diagnosed with different grades of cervical neoplasia.
METHODOLOGY: A total of 20 fresh biopsy samples were collected from clinically diagnosed cases, DNA extracted and further amplified using PCR for HPV L1 and beta globin genes. The PCR amplicons were denatured and allowed for hybridization onto a nitrocellulose strip containing the type-specific probes for 27 HPV genotypes representing both high and low risk groups as well as beta globin genes. Socio-demographic characteristics and clinical findings of the participants were recorded on structured questionnaires.
RESULTS: Amplification of HPV L1 gene by PCR detected 17 cases out of 20. Based on reverse line blot hybridization assay, the most frequent genotype identified was HPV16 (13/20). Mixed infection of HPV 16 with HPV 33, HPV 35, HPV 45 and HPV 58 was detected from other four study participants.
CONCLUSION: Human papilloma virus type 16 was the most prevalent genotype identified from the subjects screened. Further investigation with statistically sound sample size would help to clearly visualize the existing trend in Ethiopia regarding factors for high risk HPV positivity and multiple gravidity, young age at first coitus and cervical neoplasia.

Rustagi AS, Kamineni A, Weinmann S, et al.
Cervical screening and cervical cancer death among older women: a population-based, case-control study.
Am J Epidemiol. 2014; 179(9):1107-14 [PubMed] Article available free on PMC after 01/05/2015 Related Publications
Recent research suggests that cervical screening of older women is associated with a considerable decrease in cervical cancer incidence. We sought to quantify the efficacy of cervical cytology screening to reduce death from this disease. Among enrollees of 2 US health plans, we compared Papanicolaou smear screening histories of women aged 55-79 years who died of cervical cancer during 1980-2010 (cases) to those of women at risk of cervical cancer (controls). Controls were matched 2:1 to cases on health plan, age, and enrollment duration. Cytology screening during the detectable preclinical phase, estimated as the 5-7 years before diagnosis during which cervical neoplasia is asymptomatic but cytologically detectable, was ascertained from medical records. A total of 39 cases and 80 controls were eligible. The odds ratio of cervical cancer death associated with screening during the presumed detectable preclinical phase was 0.26 (95% confidence interval: 0.10, 0.63) after adjustment for matching characteristics, smoking, marital status, and race/ethnicity using logistic regression. We estimate that cervical cytology screening of all women aged 55-79 years in the United States could avert 630 deaths annually. These results provide a minimum estimate of the efficacy of human papillomavirus DNA screening-a more sensitive test-to reduce cervical cancer death among older women.

Related: Cancer Screening and Early Detection USA

Campbell JE, Thompson DM, Pate AE
Effect of the Breast and Ccervical Cancer Ttreatment Act on access to screening and treatment in Oklahoma.
J Okla State Med Assoc. 2014; 107(1):11-9 [PubMed] Related Publications
The purpose of this study was to explore the impact of Medicaid on changes in coverage among women with newly diagnosed breast cancers, in the first years of program implementation. Women and their providers used the program, with nearly double the number of women covered by Medicaid in the three years after implementation. The treatment program, as implemented in Oklahoma, reached the target population and provided coverage to women who previously had none. The study found a promising, though nonsignificant, reduction in the time between diagnosis and treatment among women diagnosed with breast cancer when Medicaid was their primary payer.

Related: Breast Cancer Cancer Screening and Early Detection USA

Loureiro J, Oliva E
The spectrum of cervical glandular neoplasia and issues in differential diagnosis.
Arch Pathol Lab Med. 2014; 138(4):453-83 [PubMed] Related Publications
CONTEXT: Premalignant and malignant glandular lesions of the cervix are known to often cause diagnostic problems with a variety of benign (more common) as well as other malignant mimics, the latter setting often being represented by secondary involvement by endometrioid endometrial carcinoma especially in small samplings.
OBJECTIVE: To highlight key histologic features and immunohistochemical markers that may be helpful in the distinction of in situ endocervical carcinoma from benign glandular proliferations, and those that separate different subtypes of invasive endocervical carcinoma, as well as invasive carcinoma from other carcinomas secondarily involving the cervix and nonneoplastic proliferations of the cervix.
CONCLUSIONS: Clinical and morphologic features as well as immunohistochemistry results should be used in conjunction in the differential diagnosis of glandular proliferations of the cervix, as correct interpretation has major clinical consequences for the patient in most instances (especially benign versus malignant). Immunohistochemical markers should be used as part of a panel of antibodies, as exceptions may occur to the usual pattern of staining, and if used singly, they may mislead the pathologist to establish a wrong diagnosis.

Related: Endometrial (Uterus) Cancer Endometrial Cancer

Huchko MJ, Leslie H, Maloba M, et al.
Factors associated with recurrence of cervical intraepithelial neoplasia 2+ after treatment among HIV-infected women in Western Kenya.
J Acquir Immune Defic Syndr. 2014; 66(2):188-92 [PubMed] Related Publications
HIV-infected women are at increased risk for recurrence of cervical dysplasia after treatment. Short-term recurrence rates may reflect treatment efficacy and therefore impact screening protocols and follow-up planning. We conducted a prospective study of 297 HIV-infected women undergoing loop electrosurgical excision procedure for cervical intraepithelial neoplasia 2+ (CIN2+) in an HIV clinic in Kisumu, Kenya. By 6 months after the procedure, 20 (7.1%) of women had recurrent CIN2+. Recurrence was significantly associated with CD4 nadir but not with highly active antiretroviral therapy use. Longer-term follow-up of this cohort will illustrate the potential impact of highly active antiretroviral therapy and immune status on CIN2/3 disease recurrence.

Yang Z, Pan X, Gao A, Zhu W
Expression of Sox2 in cervical squamous cell carcinoma.
J BUON. 2014 Jan-Mar; 19(1):203-6 [PubMed] Related Publications
PURPOSE: Sox2, one of the genes that maintains self-renewal of embryonic stem cells and relates to the differentiation potential of these cells, is abnormaly expressed in various human tumors. We investigated the expression Sox2 in normal cervix and cervical squamous cell carcinoma (SCC), and we also assessed the prognostic significance of Sox2 expression in FIGO stage I-II cervical SCC.
METHODS: Immunohistochemistry was performed to define the expression of Sox2 in 20 normal cervical tissue samples and 55 samples of cervical SCC. Correlations with clinicopathological characteristics were determined by chi-square test. The prognostic impact of Sox2 expression with regard to overall disease-free survival (DFS) was determined by the Kaplan-Meier method.
RESULTS: The positive expression rate in cervical SCC was 74.5% (41/55), while in normal cervix it was 20.0% (4/20; p=0.000. In addition, the expression of Sox2 did not correlate with clinical factors (p>0.05). The overall DFS rates with negative and positive expressions of Sox2 were 35.7 and 29.3%, respectively (p=0.360).
CONCLUSIONS: Our results show that Sox2 was overexpressed in FIGO stage I-II cervical SCC, indicating that overexpressed Sox2 may play an important role in the carcinogenesis of cervical SCC. Besides, we found that the expression of Sox2 had no relation to clinical factors and prognosis.

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