Ask your doctor for regular screening preferably every five yers for any evidence of cancer of mouth of womb & Insist on Vaccination against this dreadful disease for your daughters as son she attains 12 yrs of age.

or for five yearly screening for Cancer of uterine mouth: Mouth of Womb: Virus and Cervical Cancer Cancer Cervix

Also insist on HPV vaccinations of your daughter once she crosses 12 years of age.

Q. 1. What is the disease burden? :-Why you should be worried? What is the Global Prevalence of Cancer Cervix in 2010?

Annual new global cases:-5, 50,700 cases

Global average annual deaths: 2, 86,823 cases.

Q.2. Prevalence in India: - In India: ¼ Th of all cancer Cx cases globally seen is from India. Heavy disease burden in our poor country. These National expenses can be curtailed by routine vaccinations against this virus causing the disease (HPV Vaccine initiated at pubertal period and later by regular screening for early presence of abnormal cells in the mouth of womb.

Q. 3. Is the disease Ca Cx is preventable disease? Yes, 1) as mentioned earlier if vaccinations are duly taken and then by regular standard screening –then most of the cancers of mouth of womb can be averted.

Q.4.How to screen for the disease,–before the actual disease appears? The very philosophy is to detect cancer in its precursor stage and this screening can ideally be achieved by e.g. combined screening i.e. both by

1) Staining cells after taking cells from uterine mouth (called Pap stain)

And 2) Tests for presence of virus in secretions from mouth f womb for presence of virus (HPV) if cervical pathology is detected at PRECURSOR STAGE. Most cases, if not all cases of cancer of mouth of womb is caused by the virus infection transmitted by sexual intercourse. The name of the virus i.e. causative organism is HPV-High risk strains.   There are about 100 type of HPV virus of which humans are infested with about 40 types can infect genital tract. Of these 40 genotypes as many as 15 classes called STRAINS of HPV virus can cause Cancer of month of womb. It is said HPV 16 causes cancer cervix which are visible usually but c type 18 causes cancer inside the mouth of the cervix i.e. glands in the cervical canal. This is called Adeno carcinoma and difficult to dragons early.

Q.5. what are the different modalities of Screening worldwide?

There are three broad methods for screening which are described below e.g. 1) Tests directed for Scrape Cytology Based Screening Programs,

2) Visual Inspection Methods

And   3) Persistence of HPV (high risk strains) in Cervico-vaginal fluid.    

Q.6. what information we can receive from the different “Cervix Cancer Screening Methods”?

As said earlier that there three types of screening methods for diagnosing precursor stage of cancer of uterine mouth (.Ca Cx). The word screening means laboratory tests or other methods which do not confirm the diagnosis of cancer cervix but prompts us to go ahead for more definitive tests for confirmation of the disease.

Q.7. Describe the details of each methods and their specificity and sensitivity:-

1) “Cytology Based Screening Programs”: This method though much debated about its efficacy in detecting cancer precursors (say, limited sensitivity & poor specificity) -but has a track record of 50% reduction of invasive cancer where this age old method is followed in a community, In different countries it have been observed  over the decades that  nationwide-population based screening programme  by using this cytological method(Pap stain) by implementing  –national programme a great reduction of cancer cervix can be achieved .

This methodology was invented by George Papanicolaou way back in 1950-. This is also called as Scrape cytology. There are two special CYTOLOGY BASED SCREENING e.g. 

a)      Liquid Based Cytology (LBC) b) AutoPap/ AutoCyte Screen-Automated Pap smear.

In many countries there are organized cytology based screening programmers as mentioned earlier in those countries ca cervix can be detected at its precancerous sage (Precursor stage). Treated adequately and followed up properly such lesions will not progress to full-fledged disease of cancer Cervix.

2) Visual Based (Inspection) Screening Methods:-a) VILI: - Visual inspection by Lugols Iodine b) VIA-visual inspection of Cervix by Acetic Acid.

3)  Presence for HPV-DNA / RNA:-Tests directed for persistence of HPV (high risk strains) in genital tract i.e. Cervico-vaginal fluid. If present then consider the presence of co-factors which can lead to cancer by couple of year’s time. e.g. promiscuity, smoking, under nutrition, multiparty, presence of sexually transmitted diseases and OCP intake.

Q. 8. What are the limitations of DNA testing”?

There is low specificity and low positive predictive value of DNA testing has forced the scientists to find out some other tests to assess the activity viral oncoproteins e.g. 1) P16 ink4a –is a gene which expresses   proteins which are potent tumor suppressor.2) HTERT(Human Telomerase Reverse Transcriptase).

The problem is that mere presence of high risk strain does not mean that the virus are secreting oncoproteins and causing progressive damage to tissues affected.

Q 9.    . How HPV DNA used is tested in the decades of eighties?

The method earlier used was “Direct Probe Hybridization” e.g. dot blot and Southern Blot.

These were of low sensitivity. Currently Amplification Technology is used e.g. 1) PCR based methods and 2) Hybrid Capture 2 tests  which is highly effective in the sense that it can pick up even I small number of viruses in genital tract.

Q.10. What are the different screening tests has been evolved during the last two decades based on HPV DNA or RNA detection systems? What are the different methods of assessing DNA tests by Molecular techniques?

A) Amplification techniques:-like Hybrid Capture Methods using amplification techniques e.g.” nucleic acid probe tests”. Amplification techniques may be of three types e .g. 1) Target amplification, 2) Signal amplification : & 3)  Probe amplification 

Details are as follows:-1) Target amplification –where target nucleic acids are amplified by PCR 2) Signal amplification: HC: - In this type of amplification signal generated from each probe is enhanced by compound probe or branched probe technology (HC). & thirdly 3) Probe amplification-probe molecule itself is amplified-by ligase chain reaction.

B)   By PCR methods: Methods not using amplification techniques.e.g. PCR reactions.

:-

What type of test , in practice , is commonly done  in clinical practice in cases of suspected  HPV? PCR) –assays like 

 method- commonly are commonly employed. This method   has capacity to detect very small of HPV- DNA-i.e. high sensitivity. It can detect as small as 10 copies of HPV genomic DNA in few micro liter of sample (cervical & vaginal fluid of the woman). If method is properly used then highly concentrated sample of specific DNA genetic sequence are produced  which are then probed to identify specific HPV genotype.

Why PCR bases detection of HPV virus (causative organism of Cancer of uterine mouth) is not followed in community screening? But PCR method is generally inappropriate for large screening programmes in low resource countries because of lack of skilled persons, equipment and cost involved. 

What is carhop test?

In developed world, rapid screening method, all 14 high risk strains are screened by this method. Self collected samples possible.

Q.3. What are the indications of performing HPV DNA / RNA testing are Book-Das Gupta-Vol. 8, pp 111): -There are three main areas where HPV DNA testing have been strongly recommended.

1)      Primary screening—“Combined screening “: As a part of routine evaluation in conjunction with Pap: To witness presence of “Cervical cancer precursors” by adding DNA test as well with routine Pap. Some prefers to incorporate this HPV DNA testing as well along with routine Pap smear as a center protocol / policy matter.Thier argument is that sensitivity and speficity of Pap is low e.g. 50-86% and 92-98% only though no international organization recommend DNA testing alone or as combination with Pap. Are defected in primary screening tests by traditional cytology. If there is suggestion about abnormal cells in conventional cytology.-suspeicion of cervical cancer precursors.

2)   All Cases who exhibit Cytological evidence of ASCUS or LSIL- à Put them for DNA testing à if –ve no Treatment as double negative. Subsequently less intensive follow up. If +ve then refer for colposcopy. Triaging: -- initially one should carry out HPV DNA test and then only +vet cases should be referred for colposcopy. Triaging

3)    Follow up cases of biopsy/colposcopy:--where such procedures were adopted by reports are –vetà as follow up DNA test should be done to watch progress over the years. An s a method of follow up in cases where treatment has been done for HGIL (high grade CIN)à where ablative therapy or excision therapy has been implicated.

ASCUS-What is it?? How to follow up such cases where cytology reveals ASCUS smear??

There three available options id ASCUS +ve: - 1) Colposcopy 2) Repeat Cytology after 6 months 3) HPV DNA testing. This test will be negative in about 50% of ASCUS women. The utility of DNA testing is further evident by its 86% sensitivity and 60% referral to colposcopy and rest 40% are spared of colposcopy. So DNA testing reduces load to colposcopy units.

Few salient features about conventional Pap smear as a method of detection of precursors...

1)   Limited sensitivity (30-70%) therefore possibility of high false -ve in premalignant cases or even in malignant cases. But regarding specificity of Pap:-however most studies represent that Pap has excellent specificity in the range of 86- to near 100%).-.

How many of us believe and practice HPV testing as a primary  screening approach for cervical cancers  in low resource settings for women who are 30 yrs of age. Comparison between HPV testing alone vies a vies Cytology alone: - Firstly, HPV DNA testing is more sensitive though somewhat less specific than cytology alone so far as high grade lesions are considered. Therefore some scientist suggests that HPV DNA may be done as the first step of screening. There is minimal overdiagnosis with from HPV testing. If Hybrid Capture Technology (HC 2) if used as a tool for initial evaluation then the added benefit is that this method can detect some extra 23% of cases who are either CIN-2 compared to conventional cytology –where diag is ASCUS and LSIL. The sensitivity of HC2 for finding HSIL is as high an 89%