Understanding Your PAP Smear Results
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Understanding Your PAP Smear Results

The PAP smear is important because (in simple terms) it screens for Human Papillomavirus (HPV) & Cervical Cancer. In this article is explained how the PAP more specifically:

  • Screens for ASC-H to determines the need for colposcopy to rule out HSIL..
  • Differentiates between LSIL vs. HSIL. HSIL is indication for loop electrosurgical excision procedures (LEEP).
  • Identifies women with a negative histology, but clinical evidence of viral (e.g. HPV) persistence and risk for progression (Solomon et al, 2002). Colposcopy is indicated.

Of the many HPV subtypes, there are 4 that account for 80% of all genital warts and/or invasive cervical cancers, HPV16 & HPV18 definitively implicated in cervical dyplasias & cancer. Additional risk factors for developing cervical cancer are smoking, multiple sexual partners, DES exposure, hysterectomy for malignancy, a previously abnormal PAP, and history of sexually transmitted infections (STIs).

Ladies First Cervical Care Cycle(2011) adds: history of sexual abuse, Immunodeficiency or HIV infection, and history of non-adherence to recommended medical care. HPV is a sexually transmitted disease, so it is recommended (by Western Medicine Guidelines) that females (and males) be tested for [and vaccinated against HPV] before they become sexually active.

The PAP uses the Bethesda System (American Society of Cytopathology, 2001), which standardizes & categorizes the terminology used to report & evaluate PAP smear findings. This system has 3 major reporting elements (Ladies First, 2011):

  1. Specimen Adequacy
  2. General Categorization
  3. Interpretation of Result as:
- Negative for Intraepithelial Lesion
- Negative "Other than or reactive to"
- Positive for Squamous Abnormality
- Other Neoplasms

1. SPECIMEN ADEQUACY (Solomon et al, 2002):
  • Conventional Method (cervical scraping) = 8,000 to 12,000 cells quantified
  • Liquid-based Method (cervical wash) = 5000 cells quantified
  • Less than Adequate Specimen = lacks endocervical & squamous cells, squamous metaplasia, or endocervical transitional zone (T zone) cells.
  • Specimen Notations (Solomon et al, 2002):
-> Unlabeled specimen is always noted as unsatisfactory
-> Adequate / Inadequate number of cells from the endocervical zone. Adequate is quantified as 10 endocervical or squamous metaplastic cells.
-> Microscopy Field Obscured by blood or inflammation. An obscured field is: Satisfactory even if 50 to 75% of the epithelial cells are not visualize. Unsatisfactory when greater than 75% of the epithelial cells are not visualized.
 
2. & 3. General Categorization & Interpretation:
  • NEGATIVE INTRAEPITHELIAL LESION means there ARE NO morphological cellular changes or evidence of (squamous cell) neoplasia.  The notation “other than REACTIVE to…” is added if any cell changes that pose an epidemiological risk are due to an organism(s) or conditions:

Organisms that T zone cells can react to include:
- HPV
- Herpes simplex virus (HSV)
- Trichomonas vaginalis
- Candida species
- Vaginal flora suggestive of bacterial vaginosis or actinomyces
 
Conditions that T zone cells can react to include:
- Inflammation
- Radiation
- Intrauterine contraceptive devices (IUD)
- post hysterectomy
- perimenopausal glandular atrophy
 
  • POSITIVE SQUAMOUS CELL ABNORMALITIES:
-> Atypical Squamous Cells (ASC). All ASC abnormalities are more marked than  “ REACTIVE” finding and are suggestive of but less marked than a Squamous Cell Intraepithelial Lesion (SIL). Solomon et al (2002) state that (1) 10 to 20% of women with ASC have cervical intraepithelial neoplasia (noninvasive squamous cell abnormality), (2) 1 in 1000 women with ASC have invasive cancer, and (3) ASC has a high positive predictive value of CIN2 or CIN3 (see below).

ASC SUB- CATEGORIES:
-> Atypical Squamous Cells of Undetermined Significance- Unspecified (ASC-US).

-> Atypical Squamous Cells with High-grade Squamous Cell Intraepithelial Lesion/HSIL Not Ruled Out (ASC-H). ASC-H classification is a very important intermediary between ASC-U above and HSIL below because 5% to 10% of ASC turns out to be HSIL (Solomon et al, 2002).

  • POSITIVE SQUAMOUS INTRAEPITHELIAL LESIONS (SIL)
-> Low-grade Squamous intraepithelial Lesions (LSIL). Most cervical dysplasias that are LSIL, especially among young women, are self-limiting HPV infection with the reliability of the occurrence reproducible - unlike HSIL. (Solomon et al, 2001).

-> High–grade Squamous Intraepithelial Lesions (HSIL). These encompass moderate to severe dysplasias, carcinoma in situ, and squamous cell carcinoma. 
 
  • ATYPICAL GLANDULAR CELLS (AGC) & AGC-UNDETERMINED SIGNIFICANCE (AGC-US)The PAP smear is best to identify squamous & epithelial lesions/ cancers of the endocervix (T zone) and NOT epithelial abnormalities of glandular, endocervical, endometrial cells of the uterus and ovaries etc. Therefore, it is reported whenever endometrial glandular cells ARE found via PAP in women over 40 years old with or without SIL (Solomon et al, 2002).

Differentiating between cells of the T zone vs. cells of glandular tissue determines treatment & prognosis. So a notation is made as to whether the AGC appear favorable towards neoplasm. This is because, when identified via a PAP smear, 20% to 30% of AGCs are associated with a high-grade disease compared to ASC-US findings, and  AGCs of Undetermined Significance (AGC-US) is probably neoplastic (Solomon et al, 2002).

AGC & AGC-US SUB-CATEGORIES:
-> Atypical Cells (endocervical, endometrial, or glandular) specified or not otherwise specified (NOS)

-> Atypical Cells (endocervical, endometrial, or glandular) that favor neoplasm. Atypical endocervical cell have fewer neoplasias (Solomon et al, 2002).

-> Endocervical Adenocarcinoma in Situ

-> Adenocarcinoma (endocervical, endometrial, or extrauterine) NOS.

Reliability & Sensitivity of PAP Results
A pathologist interprets & reports PAP (and biopsy) results. The mode of analysis of the PAP cytology specimen is automated, computer generated, or via molecular testing (Solomon et al, 2001). The PAP is 68% - 80% sensitive  in detecting women with cervical intraepithelial neoplasia, but sensitivity is also dependent upon the adequacy of the PAP smear sample (National Cancer Institute, 2014).

This sensitivity means that 20% or more of women with cervical neoplasia are missed. Hence the importance of scheduled screening every 3 years or more frequently depending on the risk factors. On the other hand, testing for the presence of HPV antibodies during a PAP is 95% sensitive. Meaning only 5% of women with HPV are missed.
 
CERVICAL NEOPLASM VS. CANCER
The Cervical Intraepithelial Neoplasia (CIN) 1,2,3 Grading System is NOT used in the Bethesda PAP system. The CIN system evaluates histology (tissue appearance) via biopsy vs. PAP cytology (cell appearance) via cervical scraping/wash. Biopsy is desired when when PAP results show POSITIVE SQUAMOUS INTRAEPITHELIAL LESION (SIL) and further qualify the lesion as:
 
  • CN 1 = mild dysplasia
  • CN 2= moderate dysplasia
  • CN 3= severe dysplasia

CIN terminology can be combined with Bethesda terminology for management guidelines. For example, HPV dysplasia would be categorized as CIN1 (Solomon et al, 2002). Lower Anogenital Squamous Terminology (LAST) is another histology grading system that is combined with Bethesda terminology for anorectal tissue neoplasia.
 
The most important histological finding upon biopsy is if the dysplasia (abnormally growing) cells are invading surrounding tissue - if they are not, it is called in situ, which is technically not cancer yet (Minarsik, 2014)! Dysplasic cells upon biopsy, can appear histologically similar to-> to slightly different from -> to grossly different from their parent cells such that it is sometimes very difficult for a pathologist to determine neoplasia and tissue of origin (Minarsik, 2014) in order to diagnose:

  • endocervical adenocarcinoma/ endocervical adenocarcinoma in situ
  • endometrial adeno-carcinoma
  • extrauterine adeno-carcinoma
  • adenocarcinoma, NOS
  • adenocarcinoma in situ (AIS). There is overlap between AIS and well-differentiated invasive endocervical adenocarcinoma (Solomon et al, 2001).


INTEGRATIVE MEDICINE TIPS
  • Pearl Powder, a classical Chinese herbal formula is the focus of a Phase II study of a topical herbal cream for the treatment of HIV-related anal high-grade squamous intraepithelial lesion/aHSIL) and to prevent HPV-related anal cancer. Misha Ruth Cohen OMD LAc is a lead investigator on a team with MDs at California Pacific Medical Center, San Francisco California (Misha Ruth Cohen Education Foundation):

"...Complete lesion regression or partial regression to low-grade SIL defined as histology at 12 months (e.g., 3 months post-treatment) occurred in four (27%) patients. Two additional patients with lesion regression developed metachronous aHSIL, and a third had recurrence of aHSIL in a prior site of aHSIL ". A Pilot Study of the Safety and Feasibility of Traditional Chinese Medicine for Treatment of Anal High Grade Squamous Intraepithelial Lesions (aHSIL)".  

 
Sources
American Society of Cytopathology. The 2001 Bethesda System. In NCI Bethesda System.  Retrieved from http://nih.techriver.net/besthesdaTable.php
 
Ladies FirstObstetrics & Gynecology of Dothan. (2011). Cervicalcarecycle.  Retrieved from http://ladiesfirstproviders.vermont.gov/cervical-care/cycle (interactive web page no longer available).

Minarsik,  (2014). Neoplasms I- IV: Sessions 11-14. In Medical School Pathology. Retrieved from www.medicalschoolpathology.com/2014-2015MP4Archives/
 
National Cancer Institute. (2014). Cervical cancer screening: Description of the evidence. Retrieved from www.cancer.gov/cancertopics/pdq/screening/cervical/HealthProfessional/page2 
 
Solomon, D., Davey, D., Kurman, R., Moriarty, A., O’Connor, D., Prey, ... Young, N. (2002). The 2001 Bethesda System terminology for reporting results of cervical cytology. Journal of the American Medical Association 287:16.
 
 
 
 
 
 

 









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