Κυριακή 27 Σεπτεμβρίου 2009

anaparagwgi apo ton MAD blogger

Όταν η Επιστήμη γίνεται Προπαγάνδα (και τούμπαλιν)

Την προηγούμενη Τετάρτη, των "συλλαλητηρίων", εδώ στη Θεσσαλονίκη, είχα ανεβάσει μια photo που έδειχνε έναν αιμόφυρτο νεαρό με ένα μακό που απεικόνιζε τη σημαία των Σκοπίων. Οι bloggers της γείτονος τότε άρχισαν να μου στέλνουν διάφορα mails. Οι περισσότεροι ήταν ερειστικοί, υπήρξαν, όμως, και κάποιοι μετριοπαθείς. Μαζί τους ξεκίνησα μια e-συζήτηση περί της ονομασίας. Μάλιστα, ο Moby, ο πλέον δημοφιλής Σκοπιανός blogger (κάτι σαν τον Πρέζα εδώ), είχε καταφέρει προς στιγμήν να με κάνει να αναθεωρήσω... Φευ! Γιατί μόλις τη Δευτέρα το βράδυ ανακάλυψα τα όρια της προαπαγάνδας. Και την πραγματική του ταυτότητα. Σε ξέρω Μοby. Σε είδα. Εξηγούμαι.

Φάση 1η: Μπορεί ο καθένας να μασήσει

To mail με παρέπεμπε να διαβάσω ένα επιστημονικό άρθρο. Φυσικά, ο blogger Moby δεν ήταν σε θέση να γνωρίζει ότι εγώ είμαι γιατρός. Το ίδιο κι εγώ -δεν ήξερα ότι είναι συνάδελφος. Τα στοιχεία της δημοσίευσης:

Arnaiz-Villena A, et al. HLA Genes in Macedonians and the Sub-Saharan origin of the Greeks. Tissue Antigens 57(2); 118-127 (2001)

To link σας πηγαίνει κατευθείαν στην πηγή του άρθρου από το Medline. Για εσάς που βαριέστε ή δε γνωρίζετε την ορολογία της Ιατρικής, μεταφράζω.

Τα HLA αλληλόμοφα (Human Leukocytes Antigens ή αντιγόνα των λευκοκυττάρων του ανθρώπου. Πρόκειται για μείζον σύστημα ιστοσυμβατότητας, αυτοί οι δείκτες που τσεκάρεις αν υπάρχει συμβατότητα π.χ. στο μυελό των οστών ή στο μόσχευμα ήπατος κτλ. Μέσω αυτού μπορεί να αναγνωριστεί και η πατρότητα βλέπε Πασχάλη, αλλά και να γίνει tracking back η καταγωγή του οποιουδήποτε από εμάς) προσδιορίστηκαν σε κατοίκους των Σκοπίων με ταυτοποίηση του DNA. Οι συχνότητες των HLA-A, -B, -DR και -DQ αλληλόμορφων και οι ανεπτυγμένοι απλότυποι αυτών προσδιορίστηκαν για πρώτη φορά και τα αποτελέσματα συγκρίθηκαν με αυτά άλλων Μεσογειακών λαών, ειδικά με αυτά των γειτόνων Ελλήνων. Υπολογίστηκαν οι γενετικές αποστάσεις και καταρτίστηκαν δενδρογράμματα που δείχνουν τη σχέση των γειτονικών λαών.

Αποτελέσματα: 1) Οι "Μακεδόνες" ανήκουν στους πληθυσμούς των παλαιότερων Μεσογειακών λαών, όπως οι Ιβηρες (με τους Βάσκους), οι Βόρειοι Αφρικάνοι, οι Ιταλοί, οι Γάλλοι, οι Κρήτες, οι Εβραίοι, οι Λιβανέζοι, οι Τούρκοι, οι Αρμένιοι και οι Ιρανοί. 2) Οι "Μακεδόνες" δε σχετίζονται με αυτούς που κατοικούν στα γεωγραφικά όρια της Ελλάδας σήμερα, οι οποίοι Έλληνες δεν ανήκουν ούτε στους πληθυσμούς των παλαιότερων Μεσογειακών λαών. 3) Οι Έλληνες βρέθηκε πως έχουν συγγένεια με τους υποσαχάριους πληθυσμούς της Αιθιοπίας και αυτό ίσως εξηγείται με τη μετακίνηση και μίξη των πληθυσμών κατά την περίοδο της φαραωνικής Αιγύπτου. [Το επίμαχο δενδρόγραμμα δεξιά]

Αυτό ήταν το λεγόμενο abstract της δημοσίευσης, η περίληψη. Το κυρίως κείμενο (που και καλά πρέπει να είσαι συνδρομητής στο εν λόγω περιοδικό, για να το κατεβάσεις, αλλά όλα τα σκοπιανά ιστολόγια έχουν κομμάτια του) σου το έχω εξασφαλίσει εδώ ολόκληρο σε pdf.

Ένα χρόνο αργότερα, και στο ίδιο επιστημονικό ιατρικό περιοδικό, ο ίδιος καθηγητής δημοσιεύει το παρακάτω άρθρο.

Arnaiz-Villena A, et al. Population genetic relationship between Mediterranean populations determined by HLA allele distribution and a historic perspective. Tissue Antigens 60(2); 11-121 (2002)

Με λίγα λόγια επαναλαμβάνει τη θεωρία του ότι οι Έλληνες είναι ξεχωριστός λαός από τους Μακεδόνες και ότι οι Έλληνες σχετίζονται φυλετικά με τους Αιθίοπες, ενώ οι Μακεδόνες προϋπήρχαν στον ελλαδικό χώρο, μαζί με τους Κρήτες...

Φάση 2η: Πού νά 'ξερες σε ποιον μιλάς...

Καταρρέει ο μύθος εκ των έσω. Το 2004, σκοπιανής προέλευσης δημοσίευση στο ίδιο πάλι περιοδικό ανασκευάζει τη θεωρία και έρχεται σε σύγκρουση με την παλιότερη δημοσίευση, ακυρώνοντάς την αυτόματα. Κι ενώ στην πρώτη περίπτωση είχαμε τους "Μακεδόνες" ως ξεχωριστό λαό από τους Έλληνες και τους Έλληνες απογόνους των Ταμ Ταμ, του Σάκα και των Φαραώ, τώρα μας λένε ότι οι "Μακεδόνες" είναι αμιγώς Βαλκάνιοι και μάλιστα μοιράζονται κοινά γονίδια τόσο με τους Έλληνες, όσο και με τους Τούρκους! Αυτό, τώρα, ο απλός άνθρωπος θα το μασούσε? Δε μπορείτε να δείτε τη σκοπιμότητα? Ορίστε η πηγή:

Petlichkovski A, et al. High-resolution typing of HLA-DRB1 locus in the Macedonian population. Tissue Antigens 64(4); 486-491 (2004)

Ταλαίπωρε Moby! Δυστυχώς, όμως, την πάτησες! Στο 2ο mail που μου έστειλες, φαινόταν το όνομά σου! Περίμενες να μην παρατηρήσω ότι είναι το ίδιο με το προτελευταίο όνομα που αναφέρεται στην ομάδα του περίφημου καθηγητή Arnaiz-Villena? Και να μου το παίζεις ιστορία ότι και καλά στο Complutense Universidad de Mardid έγινε αυτή η σούπερ μελέτη που τα αποδεικνύει όλα για την ιστορικότητα της "Μακεδονίας" σας? Ε, λοιπόν, φίλτατε σε πληροφορώ ότι ΗΜΟΥΝ ΚΙ ΕΓΩ ΣΤΟ COMPLUTENSE και έλιωνα εκεί σε ένα ερευνητικό πρωτόκολλο στο τμήμα της Πειραματικής Ενδοκρινολογίας, δουλεύοντας πάνω στη γήρανση. Νομίζεις ότι δεν είχα ακούσει τίποτα για το σκάνδαλο Arnaiz-Villena? Είναι τυχαίο που το περιοδικό που δέχτηκε να δημοσιεύσει ένα κείμενο το οποιο είχε παραπομπές σε unpublished data και τηλεφωνικές επικοινωνίες έπεσε σε impact factor κατακόρυφα?

Ένα- ένα. Πρώτα το περιοδικό. Το Τissue Antigens το 2001 (έτος της επίμαχης δημοσίευσης) είχε impact factor 2,864. Δηλαδή ένα μέτριο προς καλό περιοδικό (impact factor είναι μια κλίμακα αξιολόγησης των επιστημονικών περιοδικών, ανάλογα με την επιρροή που ασκούν στην επιστημονική κοινότητα. Το 2001 το καλύτερο περιοδικό κατάφερε i.f. > 46 με την κλασική τριάδα των Lancet, Nature και Science να ακολουθούν). Τώρα το περιοδικό κατατάσσεται στα μέτριου προς χαμηλού i.f. και αυτό, γιατί προηγήθηκε το σκάνδαλο Arnaiz-Villena.

Η ιστορία ξεκίνησε με ένα άρθρο στο Τhe Guardian. Τον Antonio Arnaiz-Villena αμφισβήτησαν εξ'αρχής και οι Luca Cavalli-Sforza, Alberto Piazza και Neil Risch, οι πλεόν αναγνωρισμένοι γενετιστές. Μεταξύ άλλων δήλωσαν: "Using results from the analysis of a single marker, particularly one likely to have undergone selection, for the purpose of reconstructing genealogies is unreliable and unacceptable practice in population genetics", και κάνοντας ιδιαίτερη αναφορά στα αποτελέσματα που έδιναν για τους Έλληνες: "anomalous results, which contradict history, geography, anthropology and all prior population-genetic studies of these groups". Καμία έρευνα μέχρι σήμερα δεν έχει επιβεβαιώσει τη θεωρία του Arnaiz-Villena. ΝΕΜΕΣΙΣ. Εκτός του ότι το κύρος του καθηγητή είχε δεχτεί ανεπανόρθωτο πλήγμα, καθώς όλοι προσπαθούσαν να ερμηνεύσουν την περίεργη σχέση του με το αμερικάνικο περιοδικό, και οι δημοσιεύσεις του είχαν καταρριφθεί, ήρθε το τελειωτικό χτύπημα. Κατηγορείται για "ηθικό εκβιασμό" και εκδιώκεται από το Πανεπιστήμιο Computense της Μαδρίτης, εκδιώκεται από το Hospital Doce de Octubre (όπου ήταν επικεφαλής του τμήματος Ανασολογίας και Μοριακής Βιολογίας) και κατηγορείται για κατάχρηση 3,9 εκτομμυρίων ευρώ! ΑΥΤΟΙ ΕΙΝΑΙ ΟΙ ΑΝΘΡΩΠΟΙ ΣΑΣ ΡΕ ΑΛΑΝΙΑ?

Σάββατο 16 Μαΐου 2009

Η Ελληνική ταυτότητα !

Mr Xenophon Zolotas First speech:

``Kyrie, I eulogize the archons of the Panethnic Numismatic Thesaurus and the Ecumenical Trapeza for the orthodoxy of their axioms, methods and policies, although there is an episode of cacophony of the Trapeza with Hellas. With enthusiasm we dialogue and synagonize at the synods of our didymous Organizations in which polymorphous economic ideas and dogmas are analyzed and synthesized.
Our critical problems such as the numismatic plethora generate some agony and melancholy. This phenomenon is characteristic of our epoch. But, to my thesis, we have the dynamism to program therapeutic practices as a prophylaxis from chaos and catastrophe. In parallel, a panethnic unhypocritical economic synergy and harmonization in a democratic climate is basic.
I apologize for my eccentric monologue. I emphasize my eucharistia to you Kyrie, to the eugenic and generous American Ethnos and to the organizers and protagonists of this Amphictyony and the gastronomic symposia.''

Mr Xenophon Zolotas Second speech:

``Kyrie, It is Zeus' anathema on our epoch for the dynamism of our economies and the heresy of our economic methods and policies that we should agonise between the Scylla of numismatic plethora and the Charybdis of economic anaemia. It is not my idiosyncrasy to be ironic or sarcastic but my diagnosis would be that politicians are rather cryptoplethorists.
Although they emphatically stigmatize numismatic plethora, energize it through their tactics and practices. Our policies have to be based more on economic and less on political criteria. Our gnomon has to be a metron between political, strategic and philanthropic scopes. Political magic has always been antieconomic.
In an epoch characterised by monopolies, oligopolies, menopsonies, monopolistic antagonism and polymorphous inelasticities, our policies have to be more orthological. But this should not be metamorphosed into plethorophobia which is endemic among academic economists. Numismatic symmetry should not antagonize economic acme.
A greater harmonization between the practices of the economic and numismatic archons is basic. Parallel to this, we have to synchronize and harmonize more and more our economic and numismatic policies panethnically.
These scopes are more practical now, when the prognostics of the political and economic barometer are halcyonic. The history of our didymous organisations in this sphere has been didactic and their gnostic practices will always be a tonic to the polyonymous and idiomorphous ethnical economics.
The genesis of the programmed organisations will dynamize these policies. I sympathise, therefore, with the aposties and the hierarchy of our organisations in their zeal to programme orthodox economic and numismatic policies, although I have some logomachy with them.
I apologize for having tyrannized you with my hellenic phraseology. In my epilogue, I emphasize my eulogy to the philoxenous autochthons of this cosmopolitan metropolis and my encomium to you, Kyrie, and the stenographers. ''

' Mr Xenophon Zolotas


Κυριακή 15 Μαρτίου 2009

Εμβολιο HPV . Η αλήθεια !

HPV Vaccine Offers Cross-Protection for HPV Types Not Covered By Vaccine


Roxanne Nelson
Information from Industry
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Learn more about an important trial with patients in the early adjuvant setting. Click here.
Safety Information and Prescribing Information.

March 12, 2009 — The quadrivalent human papillomavirus (HPV) vaccine, marketed under the name Gardasil (Merck), is a recombinant vaccine that is effective against HPV types 6, 11, 16, and 18. The vaccine received approval for the prevention of cervical, vulvar, and vaginal intraepithelial lesions and genital warts associated with the vaccine HPV types, but 2 new studies indicate that the vaccine might offer protection from other types of HPV.

"There are many reasons to recommend vaccination with [the quadrivalent vaccine]," said study author Darron Brown, MD, professor of medicine, microbiology and immunology at Indiana University School of Medicine, in Indianapolis. "The most important reason is that the vaccine is safe and highly effective in reducing disease caused by the 4 HPV types, [which account for] approximately 80% of all HPV-related diseases of the genital tract. Cross-protection, although modest, indeed provides an extra benefit for young women who choose to be vaccinated."

Both studies, which appear in the April issue of the Journal of Infectious Diseases, demonstrate that vaccination provides cross-protection against nonvaccine HPV types, which are responsible for about 20% of all cervical cancers.

"The cross-protection reported in this issue of the Journal is definitely good news," writes Rolando Herrero, MD, from the Proyecto Epidemiológico Guanacaste, Fundación INCIENSA, in San José, Costa Rica, in an accompanying editorial. The "30% maximum protection against precursor lesions could reduce the burden of cervical cancer an additional 6%, compared with that afforded by the HPV16/18 vaccine."

The cross-protection reported in this issue of the Journal is definitely good news.

"This could represent ~30,000 cases worldwide, but would still not afford protection against at least 25% of cancers, making the development of safe, effective, and low-cost polyvalent vaccines a major priority for both academia and industry, to ensure success in the fight against cervical cancer," he notes.

Reduces Infection Rate of Nonvaccine Types

In the first study, Dr. Brown and colleagues evaluated whether the quadrivalent vaccine would protect against infection and disease caused by 10 HPV types not included in the vaccine. The majority of known HPV types that infect the genital tract are members of the Alphapapillomavirus (or A) genus; of this group, 18 have been classified as oncogenic on the basis of epidemiologic and/or genetic evidence. HPV16 is the prototype of the A9 species, the researchers note, which includes 6 cancer-causing types (16, 31, 33, 35, 52, and 58), whereas HPV18 is the prototype of the A7 species, which includes 5 cancer-causing types (18, 39, 45, 59, and 66).

To analyze disease end points, the researchers used the database from the phase 3 FUTURE I and II clinical trials, which examined the efficacy of the quadrivalent HPV vaccine in 17,622 women aged 16 to 26 years (although there were two 15-year-old girls). The study participants were followed for a mean of 3.6 years after the first vaccine dose.

All of the women underwent cervicovaginal sampling and Pap smears at regular intervals for up to 4 years, and the analyses were conducted only on individuals who were negative for 14 HPV types on day 1. HPV genotyping was performed for biopsy samples, and histologic diagnoses were determined with a pathology panel.

The researchers found that the quadrivalent vaccine reduced the incidence of infection with HPV types 31 and 45 by 40.3% (95% confidence interval [CI], 13.9% to 59%), and related cervical intraepithelial neoplasia (CIN) 1–3/adenocarcinoma in situ (AIS]) by 43.6% (95% CI, 12.9% to 64.1%). It also decreased CIN1–3/AIS by 29.2% (95% CI, 8.3% to 45.5%), relative to HPV types 31, 33, 45, 52, and 58.

Overall, vaccine efficacy for CIN1–3/AIS associated with the 10 tested nonvaccine HPV types was 23.4%, and was 32.4% for high-grade lesions (CIN2–3/AIS), and was driven primarily by reductions in HPV types 31,33, 52, and 58.

Demonstrates Efficacy in Women With Pre-Existing HPV Infection

A related intention-to-treat analysis, led by Cosette Wheeler, PhD, professor of molecular genetics and microbiology at the University of New Mexico School of Medicine, in Albuquerque, examined the cross-protective vaccine impact for the same 10 nonvaccine HPV types. They also used the FUTURE I and II database, but in this study, the cohort included both HPV-naïve women and women with pre-existing HPV infection and/or HPV-related disease at enrollment.

They found that vaccination reduced the infection rate of HPV types 31, 33, 45, 52, and 58 by 17.7% (95% CI, 5.1% to 28.7%) and of CIN1–3 or AIS by 18.8% (95% CI, 7.4% to 28.9%). The quadrivalent vaccine also reduced the rate of HPV types 31, 58, and 59–related CIN1–3/AIS by 26.0%, 28.1%, and 37.6%, respectively.

Although a small decrease in HPV types 31, 33, 45, 52, and 58–related CIN2 or worse was observed, the estimated reduction was not found to be statistically significant.

The authors point out that nearly one third (32.8%) of the FUTURE I and II trial participants were infected, at the time of study enrollment, with 1 or more of the genital HPV types under evaluation for vaccine cross-protection. "Despite prevalent oncogenic HPV infections with vaccine and nonvaccine HPV types, cross-protective vaccine efficacy against infection was observed for both composite end points, as well as the individual HPV types 31 and 59," they write.

Vaccine Duration Not Yet Determined

"We don't know how long the high degree of protection will last, since there are very few cases of disease in vaccinated women," Dr. Brown told Medscape Oncology. "It is possible that a booster may eventually be desirable, but it is also possible that the high degree of protection elicited by [the quadrivalent vaccine] is life-long."

We have shown evidence of immune memory in young women vaccinated with [the quadrivalent vaccine].

"However, we have shown evidence of immune memory in young women vaccinated with [the quadrivalent vaccine]," he added. "This is important because immune memory is critical for long-lasting protection, as we expect to see in women vaccinated with [the quadrivalent vaccine]."

Long-term data are not yet available. "The phase 3 trials began in late 2002, and therefore some participants have been followed for more than 6 years," said Dr. Brown, adding that the next trials will probably be conducted in boys and men, and in sexually active women older than 26 years of age.

Both studies were designed and sponsored by Merck Research Laboratories. A number of authors from both studies have relationships with Merck, GlaxoSmithKline, and Sanofi Pasteur. These include receiving consulting fees, advisory board fees, grant support, and lecture fees. Several authors are also employees of Merck. See papers for details.

Τετάρτη 11 Μαρτίου 2009

Η ευθύνη να είσαι γυναίκα !


Pap Test
Key Points
  1. What is a Pap test?
  2. The Pap test (sometimes called a Pap smear) is a way to examine cells collected from the cervix (the lower, narrow end of the uterus). The main purpose of the Pap test is to detect cancer or abnormal cells that may lead to cancer. It can also find noncancerous conditions, such as infection and inflammation.

  3. What is a pelvic exam?
  4. In a pelvic exam, the uterus, vagina, ovaries, fallopian tubes, bladder, and rectum are felt to find any abnormality in their shape or size. During a pelvic exam, an instrument called a speculum is used to widen the vagina so that the upper portion of the vagina and the cervix can be seen.

  5. Why are a Pap test and pelvic exam important?
  6. A Pap test and pelvic exam are important parts of a woman’s routine health care because they can detect abnormalities that may lead to invasive cancer of the cervix. These abnormalities can be treated before cancer develops. Most invasive cancers of the cervix can be prevented if women have Pap tests regularly. Also, as with many types of cancer, cancer of the cervix is more likely to be treated successfully if it is detected early.

  7. Who performs a Pap test?
  8. Doctors and other specially trained health care professionals, such as physician assistants, nurse midwives, and nurse practitioners, may perform Pap tests and pelvic exams. These individuals are often called clinicians.

  9. How is a Pap test done?
  10. A Pap test can be done in a doctor’s office, a clinic, or a hospital. While a woman lies on an exam table, the clinician inserts a speculum into her vagina to widen it. A sample of cells is taken from the cervix with a wooden scraper and/or a small cervical brush. The specimen (or smear) is placed on a glass slide and preserved with a fixative, or is rinsed in a vial of fixative, and is sent to a laboratory for examination.

  11. How often should a woman have a Pap test?
  12. Women should talk with their clinician about when and how often they should have a Pap test. Current general guidelines recommend that women have a Pap test at least once every 3 years, beginning about 3 years after they begin to have sexual intercourse, but no later than age 21. Experts recommend waiting about 3 years after the start of sexual activity to avoid overtreatment for common, temporary abnormal changes. It is safe to wait 3 years, because cervical cancer usually develops slowly. Cervical cancer is extremely rare in women under age 25.

    Women ages 65 to 70 who have had at least three normal Pap tests and no abnormal Pap tests in the last 10 years may decide, after talking with their clinician, to stop having Pap tests. Women who have had a hysterectomy (surgery to remove the uterus and cervix) do not need to have a Pap test, unless the surgery was done as a treatment for precancer or cancer.

  13. When should the Pap test be done?
  14. A woman should have this test when she is not menstruating; the best time is between 10 and 20 days after the first day of the last menstrual period. If her period starts on the day of the test, she should call the doctor right away and reschedule the appointment. For about 2 days before a Pap test, she should avoid douching or using vaginal medicines or spermicidal foams, creams, or jellies (except as directed by a physician). These may wash away or hide abnormal cells. Also, a woman should not have sexual intercourse for 1 to 2 days before a Pap test, because this may cause unclear results. After the test, she can go back to her normal activities and return to work right away.

  15. How are the results of a Pap test reported?
  16. Most laboratories in the United States use a standard set of terms called the Bethesda System to report test results. Under the Bethesda System, Pap test samples that have no cell abnormalities are reported as “negative for intraepithelial lesion or malignancy.” Samples with cell abnormalities are divided into the following categories:

    • ASC—atypical squamous cells. Squamous cells are the thin flat cells that form the surface of the cervix. The Bethesda System divides this category into two groups:

      1. ASC–US—atypical squamous cells of undetermined significance. The squamous cells do not appear completely normal, but doctors are uncertain about what the cell changes mean. Sometimes the changes are related to human papillomavirus (HPV) infection (see Question 13). ACS–US are considered mild abnormalities.

      2. ASC–H—atypical squamous cells cannot exclude a high-grade squamous intraepithelial lesion. The cells do not appear normal, but doctors are uncertain about what the cell changes mean. ASC–H may be at higher risk of being precancerous.

    • AGC—atypical glandular cells. Glandular cells are mucus-producing cells found in the endocervical canal (opening in the center of the cervix) or in the lining of the uterus. The glandular cells do not appear normal, but doctors are uncertain about what the cell changes mean.

    • AIS—endocervical adenocarcinoma in situ. Precancerous cells are found in the glandular tissue.
    • LSIL—low-grade squamous intraepithelial lesion. Low-grade means there are early changes in the size and shape of cells. The word lesion refers to an area of abnormal tissue. Intraepithelial refers to the layer of cells that forms the surface of the cervix. LSILs are considered mild abnormalities caused by HPV infection.

    • HSIL—high-grade squamous intraepithelial lesion. High-grade means that there are more marked changes in the size and shape of the abnormal (precancerous) cells, meaning that the cells look very different from normal cells. HSILs are more severe abnormalities and have a higher likelihood of progressing to invasive cancer.

  17. How common are Pap test abnormalities?
  18. About 55 million Pap tests are performed each year in the United States. Of these, approximately 3.5 million (6 percent) are abnormal and require medical follow-up.

  19. What do abnormal results mean?
  20. A physician may simply describe Pap test results to a patient as “abnormal.” Cells on the surface of the cervix sometimes appear abnormal but are very rarely cancerous. It is important to remember that abnormal conditions do not always become cancerous, and some conditions are more likely to lead to cancer than others. A woman may want to ask her doctor for specific information about her Pap test result and what the result means.

    There are several terms that may be used to describe abnormal results.

    • Dysplasia is a term used to describe abnormal cells. Dysplasia is not cancer, although it may develop into very early cancer of the cervix. The cells look abnormal under the microscope, but they do not invade nearby healthy tissue. There are four degrees of dysplasia, classified as mild, moderate, severe, or carcinoma in situ, depending on how abnormal the cells appear under the microscope. Carcinoma in situ means that abnormal cells are present only in the layer of cells on the surface of the cervix. However, these abnormal cells may become cancer and spread into nearby healthy tissue.

    • Squamous intraepithelial lesion (SIL) is another term that is used to describe abnormal changes in the cells on the surface of the cervix. The word squamous describes thin, flat cells that form the outer surface of the cervix. The word lesion refers to abnormal tissue. An intraepithelial lesion means that the abnormal cells are present only in the layer of cells on the surface of the cervix. A doctor may describe SIL as being low-grade (early changes in the size, shape, and number of cells) or high-grade (precancerous cells that look very different from normal cells).

    • Cervical intraepithelial neoplasia (CIN) is another term that is sometimes used to describe abnormal tissue findings. Neoplasia means an abnormal growth of cells. Intraepithelial refers to the layer of cells that form the surface of the cervix. The term CIN, along with a number (1 to 3), describes how much of the thickness of the lining of the cervix contains abnormal cells.

    • Atypical squamous cells are findings that are unclear, and not a definite abnormality.

    Cervical cancer, or invasive cervical cancer, occurs when abnormal cells spread deeper into the cervix or to other tissues or organs.

  21. What if Pap test results are abnormal?
  22. If the Pap test shows an ambiguous or minor abnormality, the physician may repeat the test to determine whether further follow-up is needed. Many times, cell changes in the cervix go away without treatment. In some cases, doctors may prescribe estrogen cream for women who have ASC–US and are near or past menopause. Because these cell changes are often caused by low hormone levels, applying an estrogen cream to the cervix for a few weeks can usually help to clarify the cause of the cell changes. If the Pap test shows a finding of ASC–H, LSIL, or HSIL, the physician may perform a colposcopy using an instrument much like a microscope (called a colposcope) to examine the vagina and the cervix. The colposcope does not enter the body. During a colposcopy, the physician may coat the cervix with a dilute vinegar solution that causes abnormal areas to turn white. If the colposcopy finds abnormal tissue, the physician may perform endocervical curettage or a biopsy. Biopsy is the removal of cells or tissues from the abnormal area for examination under a microscope. Endocervical curettage is a type of biopsy that involves scraping cells from inside the endocervical canal with a small spoon-shaped tool called a curette.

    If the testing shows abnormal cells that have a high chance of becoming cancer, further treatment is needed. Without treatment, these cells may turn into invasive cancer. Treatment options include the following:

    • LEEP (loop electrosurgical excision procedure) is surgery that uses an electrical current which is passed through a thin wire loop to act as a knife.

    • Cryotherapy destroys abnormal tissue by freezing it.

    • Laser therapy is the use of a narrow beam of intense light to destroy or remove abnormal cells.
    • Conization removes a cone-shaped piece of tissue using a knife, a laser, or the LEEP technique.
  23. How do terms for Pap test abnormalities compare, and which tests and treatment options may be appropriate?
  24. Pap Test Result
    Abbreviation
    Also Known As Tests and Treatments May Include
    Atypical squamous cells–undetermined significance
    ASC–US


    • HPV testing
    • Repeat Pap test
    • Colposcopy and biopsy
    • Estrogen cream
    Atypical squamous cells–cannot exclude HSIL
    ASC–H

    • Colposcopy and biopsy
    Atypical glandular cells
    AGC

    • Colposcopy and biopsy and/or endocervical curettage
    Endocervical adenocarcinoma in situ
    AIS

    • Colposcopy and biopsy and/or endocervical curettage
    Low-grade squamous intraepithelial lesion
    LSIL
    • Mild dysplasia
    • Cervical intraepithelial neoplasia–1 (CIN–1)
    • Colposcopy and biopsy
    High-grade squamous intraepithelial lesion
    HSIL
    • Moderate dysplasia
    • Severe dysplasia
    • CIN–2
    • CIN–3
    • Carcinoma in situ (CIS)
    • Colposcopy and biopsy and/or endocervical curettage
    • Further treatment with LEEP, cryotherapy, laser therapy, conization, or hysterectomy

  25. How are human papillomaviruses associated with the development of cervical cancer?
  26. Human papillomaviruses (HPVs) are a group of more than 100 viruses. Some types of HPV cause the common warts that grow on hands and feet. Over 30 types of HPV can be passed from one person to another through sexual contact. Some of these sexually transmitted HPVs cause wart-like growths on the genitals but do not lead to cancer. About 15 sexually transmitted HPVs are referred to as “high-risk” because they are more likely to lead to the development of cancer.

    HPV infection is the primary risk factor for cervical cancer. About 6 million new genital HPV infections occur each year in the United States. However, although HPV infection is very common, only a very small percentage of women with untreated HPV infections develop cervical cancer.

  27. Who is at risk for HPV infection?
  28. HPV infection is more common in younger age groups, particularly among women in their late teens and twenties. Because HPVs are spread mainly through sexual contact, risk increases with number of sexual partners. Women who become sexually active at a young age, who have multiple sexual partners, and whose sexual partners have other partners are at increased risk. Women who are infected with the human immunodeficiency virus (HIV) are also at higher risk for being infected with HPVs and for developing cervical abnormalities. Nonsexual transmission of HPVs is rare. The virus often disappears but sometimes remains detectable for years after infection.

  29. Does infection with a cancer-associated type of HPV always lead to a precancerous condition or cancer?
  30. No. Most HPV infections appear to go away on their own without causing any kind of abnormality. However, persistent infection with cancer-associated HPV types increases the risk that mild abnormalities will progress to more severe abnormalities or cervical cancer. With regular follow-up care by trained clinicians, women with precancerous cervical abnormalities can be treated before cancer develops.

  31. Do women who have been vaccinated against HPVs still need to have Pap tests?
  32. Yes. Pap tests continue to be essential to detect cervical cancers and precancerous changes, even in women who have been vaccinated against HPVs.

    The U.S. Food and Drug Administration (FDA) recently approved Gardasil®, a vaccine that is highly effective in preventing infection with four types of HPV. Two of these four HPVs cause about 70 percent of cervical cancers, and the other two HPVs cause about 90 percent of genital warts (1). Another promising vaccine, Cervarix™, is being tested but is not yet approved by the FDA. These vaccines do not protect against all HPV types that cause cervical cancer. In addition, they do not protect or treat women who are already infected with HPV. Therefore, it is important for vaccinated women to continue to undergo cervical cancer screening as is recommended for women who have not been vaccinated.

  33. Have any studies been done to examine HPV testing and treatment options for mild Pap test abnormalities?
  34. The National Cancer Institute (NCI), a component of the National Institutes of Health (NIH), funded and organized the ASCUS/LSIL Triage Study (ALTS), a major clinical trial (research study with people). Findings of the trial indicate that performing an HPV test on cervical samples from women with ASC–US is more efficient than performing an immediate colposcopy or a repeat Pap test for identifying which ASC-US abnormalities need treatment. In women with ASC-US, a negative HPV test can provide reassurance that cancer or a precancerous condition is not present.

  35. What are false positive and false negative results?
  36. The Pap test is a screening test and, like any such test, it is not 100 percent accurate. Although false positive and false negative results do not occur very often, they can cause anxiety and can affect a woman’s health.

    A false positive Pap test means that a patient is told she has abnormal cells, but the cells are actually normal. A false negative Pap test occurs when a specimen is called normal, but the woman has a significant abnormality that was missed. A false negative Pap test may delay the diagnosis and treatment of a precancerous condition. However, regular screening helps to compensate for the false negative result. If abnormal cells are missed at one time, chances are good that the cells will be detected the next time.

  37. What methods are being developed to improve the accuracy of Pap tests?
  38. In April 1996, the Consensus Development Conference on Cervical Cancer, which was convened by the NIH, concluded that about half of false negative Pap tests are due to inadequate specimen collection. The other half are due to a failure to identify or interpret the specimens correctly. Although the conventional Pap test is effective in the majority of cases, the conference made it clear that new methods of collecting and reading specimens are needed to reduce the number of false negatives.

    The Bethesda System requires laboratories to determine whether there are enough cervical cells in the specimen to make a proper evaluation. This requirement helps improve the quality of samples and sample collection. The Bethesda System requires a sample to be categorized as “satisfactory for evaluation” or “unsatisfactory for evaluation.”

    One new method of collecting and analyzing samples is called liquid-based thin-layer slide preparation. This method may make it easier to screen for abnormal cells. Cervical cells are collected with a brush or other collection instrument. The instrument is rinsed in a vial of liquid preservative. The vial is sent to a laboratory, where an automated thin-layer slide device prepares the slide for viewing. Results of this method suggest that it is comparable to, or more sensitive than, standard Pap tests for the detection of significant abnormalities.

    Computer automated readers are also being used to improve the reading of Pap tests. This technology uses a microscope that conveys a cellular image to a computer, which analyzes the image for the presence of abnormal cells.

Selected Reference

  1. Koutsky LA, Ault KA, Wheeler CM, et al. A controlled trial of a human papillomavirus type 16 vaccine. New England Journal of Medicine 2002; 347(21):1645–1651.

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