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ESSAY 165 - CERVICAL CANCER

Posted by hassan M.
Cervical screening programme fulfills the WHO criteria of screnning programme and has brought down the mortality rate to a certain extent but still approximately 2000 new cases are diagnosed each year.NHSCP has introduced a new guideline in April 2004 with a hope that morbidity and mortality from cx cancer could be brought down further by identifying and treating premalignant stages but still new cases will continue to appear due to certain problems which are still difficult to tackle.
Creating awareness among women regarding smoking ,younger age at first coitus ,multiple partners,HPV infections through magazines ,TV and media and importance to attend for smears when called should be emphasized .Cervical screening programme has increased the age for first call from 20 years to 25 years till 49 years 3 yearly then 5 yearly till 65 years of age.The rationale behind is that the incidence of reverting to normal smear spontaneously is high in younger women and it was not cost effective to screen girls below 25 years however the girls who became sexually active by the age of 14,15 will have a very late first smear and premalignancy may be diagnosed for them at very first smear.
GPs should be tought to take smears properly and arrangement should be made to inform and remind to attend for smears when due but a large number of population default either due to not knowing the importance of it or are travellers. Introduction of LBC has reduced the incidence of false positive smears from 9% to 2% but the facilities are not available at all the laboratories and need traing of staffs.HPV triaging is proposed to women with moderate dyskaryosis or who has persistant HPV and do not revert to normal .HPV is found to be responsible for cx cancer in 95%of cases mostly due to HPV 16,18,31,32,52 subtypes.It can be identified with PCR and hybrid capture II but these facilities are not available and not cost effective in short term but done once in 10 years will prove cost effective in long term as compared to routine cervical screening . HPV vaccine will be available soon for high risk population but still is in research phase.
Prompt referrals for colposcopy should be done according to guide line that is if 3 border line smears and on detecting 1 moderate or severe dyskaryosis.Mild dyskaryosis should have a repeat smear after 6 weeks if still abnormal to be refered for colposcopy some clinician like to refer for colposcopy on on first mild dyskaryosis as 30%may still need colposcopy and may progress to moderate and 25%may progress to cx cancer in 10 years.However it may increase the workload and long waiting time for colposcopy and is not cost effectiveas as almost 50%may revert to normal smears.Patient should be send for urgent colposcopy in case invasion is suspected.
Colposcopy should be done by a trained professional and if difficult situation arise as during pregnancy or suspicious lesion help of experts should be asked for.Biopsies taken should involve the whole of transformation zones and LLETZ or NETZ would be ideall as tissue would be available for histo pathological diagnosis as compared to diathermy or cryocautry.If biopsy is insuffeciaent repeat biopsy should be taken .Follow up is done by yearly smears for 5 years in case of premalignant condition is treated and return to normal recall once 3 smears are normal.
There is need to ask woman regarding when she had her last smear taken on all occasions including booking for pregnancy and if she had defaulted any call smear should be collected but if she is having her smears regularly there is no need to take opportunistic smears at inserting IUCD ,at TOPor when attending Gum clinics.
A women should be discharged from the screening programme at the age of 65 years when previous
smears during last 10years are normal .Vault smears are not needed if hysterectomy was done for benign codition eg fibroids and menorrhagia. Following the screening programme strictly still may not be able to make it a thing of past as new cases will continue to appear. HPV vaccine may be able to do that but a long time is needed till it is implemented as a routine like Rubella vaccine.
Posted by Rani M.
The incidence of cervical cancer and mortality due to it in U.K. has fallen markedly over the years since the introduction of NHS cervical screening programme and its call and recall system.This has been due to reduction in both the incidence of cervical cancer and in proportion of more advanced disease. Other factors which has also contributed to reduction in mortality are: management of malignant cases in the Cancer units ( stage Ia) and gynecology oncology centers, introduction of cisplatinum based chemotherapy, improvements in imaging techniques such as MRI to detect parametrial disease & nodes.

Screening for cervical carcinoma satisfies all the WHO criteria of screening. It has a long known natural history, cervix is amenable to visualisation & screening , has a known premalignant stage, treatment of which can reduce the incidence of cervical cancer.Currently the proportion of U.K. population which undergoes screening is about 84 % All sexually active women in the 20 - 64 year age group undergoes screening at 3 yearly interval( england & wales)Screening for cervical cancer by PAP smear is safe, simple, acceptable, reliable and cost effective.

There is evidence that survival is better when surgeries for malignancies are done by gynecology oncologists rather than by general gynecologists. Management by a multidisciplinary team comprising of Gynecology oncologists, surgery and medical oncologist, radiotherapists, radiologist,pathologist , macmillan nurses and palliative care team has lead to better management of cervical cancers and helped in reduction in mortality.

Introduction of chemoradiation using cis platinum based therapy has improved the survival significantly in woman with stage Ib2 onwards. Although long term folow up for morbidity of this combined approach is required, it is seen that chemoradiaton is superior to radiation alone in terms of survival advantage.

PAP smear has a specificity of 98% and sensitivity of 51 %.but it is not 100% accurate, there are false positive (2%) and false negatives(15%). This means some woman who will subsequently develop cervical cancer are falsely tested negative and go on to develop cancer despite participating in the programme
.
Further improvements may be possible by regular training in the technique of smear undertaking, quality control of labs , target setting for G.Ps( to improve the coverage over 87 % ) and regular audit of their results by cytopathologists.

Liquid based cytology is recommended by NICE to reduce false positive and false negatives. LB.C. involves taking smear by a plastic device, from which cells wash off more easily than conventional wooden spatula, multiple smears can be made from centrifuged specimens and some can be stored, smear made has a clear background and is thus more easy for interpretation.Supernatent from the specimen lends itself to the potential for H.P.V. testing.Though many organisational changes will be required like training of staff , in longer run it may be more cost effective by reducing both false negatives, and unsatisfactory smears and inclusion of HPV testing.

99.7% of cervical cancer cases are found positive for H.P.V.Thus it is suggested that testing for HPV will help in triaging women into high and how risk category according to their HPV staus.Testing for HPV has a high negative predictive value.Screening may begin at 25 years and be carried out initially 3 yearly with LBC with the addition of HPV testing at the age of 37 years. If HPV testing is negative interval can be increased to 6 years and then woman can be discharged earlier from the programme(49 years).

Awareness regarding lifestyle high risk factors for cervical cancer and implementing changes may also help in reducing the incidence and consequently mortality due to cervical cancer.Education regarding having stable relationships, avoiding multiple sexual partners, safe sex practices to minimise risk of sexually transmitted infections ( Chlamydia, herpes simplex and HIV are all implicated in increasing the risk).Stopping smoking and male circumcision are suggested but may not be possible and their role is not clear.

Certain biological molecular factors such as cyclinns, p53, CEA may in future be helpful in early diagnosis of precancerous cases where smear is doubtful.
Thus it can be concluded that though mortality due to cervical cancer has reduced drastically, there is still room for improvements.
Posted by manjula C.
Carcinoma of cervix was a leading cause of death due to gynaecological disease among women in UK in the past but the previous decade has seen a considerable reduction in deaths due to this illness.This being reduced to <1500 cases per year from 4000per year.However it still remains a leading cause of death in developing countries .
This reduction in mortality is due to the less appearance of invasive disease and availability of better treatment modalities.
The credit of reducing the mortality goes to NHS in implementing effective screening measures in detecting preinvasive lesions.Carcinoma of cervix is an illness which effectively fits in the WHO?s requirements of a screening test,by having known the natural history,a preinvasive stageCIN having a long latent period of nearly a decade before becoming invasive,availability of a screening test which is costeffective and sensitive.
Cervical cytology though was implemented in 1967 in UK,it was not effectively used.This was reflected by a high false negatives,less awareness among the public and non reducing mortality.In 1987,NHS revised its measures by introducing a computerized call and recall system where in women are regularly called for smears by G.Ps,GPs were being given specific targets to achieve,training of cytologists to give better reports.These measures have tremendously helped in reducing the incidence of invasive illness,thereby indirectly reducing the mortality.
At present nearly 4 million women undergo smers anaually.Recently NHS has started introducing LBC a recent technology in cytology at certain pilot centres in U.K.LBC though expensive technically ,it gives better results by reducing the inadequate smears from 23% to 5%.This is a very effective step which reduces the number of false negatives and improves positive predictive value of cytology.On the long run it is found to be cost effective.
Introduction of HPV detection in high risk women also is introduced.Off late there is a rising trend of cancerr cervix in the younger age group of 25-39 yrs,in whom especially HPV testing helps in directing mild dyskaryosis and borderline smears for colposcopy
Recently there is ongoing research in the production ofeffective vaccines against HPV which is likely to reduce the incidence of cancer cervix-cervarix-from glaxo. However large clinical trials are awaited before introducing them .
There is increasing public awareness also contributing to the success of the screening programmes and also changing lifestyle ,use of barrier contraception also has helped.
However ,not only the reduction in invasive disease has contributed in reducing the mortality,but also availability of effective modes of treatment also has helped.CIN and early stage carcinomas can be effectively treated by either surgery or radiotherapy ,almost achieving 100% cure rate with minimum recurrence and better quality of life.availability of multidisciplinary approach to the patints,better referral system and expertise in treatment all have contributed to increase the survival rates.
However recently there is a rising trend seen in adenocarcinoma and adenosquamous carcinoma.This could be due to the less knowledge regarding natural history,apparent increase due to a fall in squamous cell cancer,or nonavailability of better screening techniques in detection of CGIN..Despite effective screening measures there is a rising trend of squamous cellcancer in younger age of 25-39yrs which needs to be handled effectively.
Posted by Nitin P.
Mortality due to cervical cancer has been reducing. This is because of identification and treatment at precancerous stage, early treatment once disease has set in and also better surgical and radiotherapy management.
However it still remains a major public health problem.
The cervical screening programme is aimed at identification and treatment of preinvasive stages. However, the natural history of cervical cancer is not absolutely defined, thus some cases of invasive cancer may arise after a short or absent cervical intraepithelial neoplasia stage. But on the other hand only 30 % of CIN III are believed to progress to Ca cervix over 20 years.
An ideal screening test should have a 100% sensitivity and specificity, which with cervical smears is 50% sensitivity and 90% specificity. Thus, cases would be missed because of the inherent low sensitivity.
The method of smear taking should be ideal, so that the sensitivity is improved. This involves training and education of smear takers.
Smear examination is a tedious process, and high degree of human error is present.
The uptake of the screening programme is 85% of women will have had a smear in the last 3 years. This needs to be further improved upon. Public education regards the importance of smears is thus important.
Appropriate referrals, and as per new guidelines referral to colposcopy after even mild dyskariosis needs to be followed. Also the follow up after treatment should be strictly adhered, i.e. smears for 10 years after CIN II and CIN III. This is aimed at identifying more recurrent disease and hence reduce risk of developing invasive cancer.
Thus although progress has been made with early diagnosis draw backs do remain. Liquid based cytology has the ability to improve the sensitivity and also to reduce the number of inadequate smears, thus reducing load on health care system. HPV screening will further define those women who are more likely to develop ca and thus restrict more intensive screening to these women.
Better surgical techniques, reduction in anaesthetic mortality, thromboprophylaxis, antibiotic prophylaxis and blood transfusion facilities have helped make surgical treatment of stage I A, B and II A safer than in the past. Post operative sepsis related mortality has also been reduced with use of better and appropriate antibiotics.
Centralisation of care at gynaecology cancer centres for all cases other than carcinoma in situ has also helped reduce mortality.
Radiotherapy is used for stage II B and beyond, improved techniques with RT have also reduced mortality.
The role of neo adjuvant chemotherapy is not clear at present and is used only in trials at present, hence cannot be commented to reducing the mortality.
Use of surgery and radiotherapy appropriately in recurrent cases, further improves survival rates and hence reduces mortality.
Improvements in screening, treating of preinvasive leions, public health education, and training of staff will help further reduce mortality. Biological behaviour of tumours however is different in each case with probably slow disease being picked up on screening and fast disease is missed. Thus, inspite of good screening some cases will still be seen at a late stage.
Posted by Vandana D.
Mortality from sq. cell cervical carcinoma has reduced considerably since the introduction & implementation of cervical screening programmes.Currently deaths from it have reduced to ~<1000/yr.

Many factors have contributed to this significant achievement.Better understanding of disease,greater awareness,cervical screening as mentioned before,High risk HPV DETECTION in crevical smears,recommendations for appropriate management of mild/indeterminate smears-colposcopy,HPE of directed biopsy.
Availability of sophisticated instruments (loop,laser,needle)to treat premalignant lesions so that they provide adequate material for HPE & DEFINITIVE diagnosis.

Oncology centres,imaging techniques-MRI (valuable in detection of volume of &metastasis ) ,less radical surgery,improved radiotherapy devices & techniques,combination of radiotherapy & chemotherapy in advanced disease,multidisciplinary management-gyn oncologist,med onco.,radiotherapist,radiologist,pathologist,palliative care team.Follow up by regular cervical cytology to detect residual /recurrent disease.

BUT more efforts are required to further reduce the incidence,morbidity & mortality.
Use of LBC instead of conventional cytology,as the former improves adequacy of smear,also provides material for HPV testing,equipment & training of doctors taking smears,; testing for HPV as it has high neg.predictive value(>99%),this would make screening programme more accurate.Though it involves greater costs but surely cost effective. Cervical cytology poor senstivity-~50%.

Regular audits to improve standards- detect areas of impovement.Implement improvement strategies effectively.


Immunocompromised patients,treated cases of CIN/invasive cancer to be followed & screened appropriately-6 monthly/yearly.

Education /increase awareness by printed leaflets,magazines,media-adoption of healthy life style habits-use of barrier contraceptives,avoidance of- multiple sexual partners & early sexual activity.

Future is to look for availability of HPV Vaccines,automated rather than manual smear taking,improved markers of disease,improved Tt.