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| | #REDIRECT [[Paper - The Sexual Cycle in the Human Female as revealed by Vaginal Smears (1933)]] |
| Papanicolaou GN. [[Paper - The Sexual Cycle in the Human Female as revealed by Vaginal Smears|'''The Sexual Cycle in the Human Female as revealed by Vaginal Smears''']]. Am J Anat. 1933;52: 519–637.
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| {{Historic Disclaimer}}
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| {| class="wikitable mw-collapsible mw-collapsed"
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| ! Online Editor
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| |-
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| | [[File:Mark_Hill.jpg|90px|left]] These are currently some of the plates from the historic paper by George Papanicolaou (1883 – 1962) the pathologist who developed the diagnostic "Pap smear" test named after him. Originally a Greek clinician (Georgios Nikolaou Papanikolaou) he travelled throughout Europe before becoming in 1913 an American researcher. His first studies were in other species (Guinea-Pig) before extending the studies onto humans. This paper described the appearance of normal cell smears during the different stages of the menstrual cycle. The true value of the "Pap smear" test was the identification of abnormal cells associated with cytopathology of cancer of the cervix.
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| The original black and white photomicrographs were hand-coloured by the author to match his microscopic observations.
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| {{Menstrual_Links}}
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| =The Sexual Cycle In The Human Female As Revealed By Vaginal Smears=
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| George N. Papanicolaou
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| Department of Anatomy, Cornell University Medical College, and Woman’s Hospital, New York City
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| :This work has been aided by the Committee for Research on Sex Problems of the National Research Council, and by the National Committee on Maternal Health.
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| Three Figures and Ten Plates (Eighty-One Figures)
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| ==I. Introduction==
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| The study of the female sexual functions in mammals has been greatly stimulated and advanced in recent years by the
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| application of the vaginal smear method. This method, as
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| originally applied to the guinea pig by Stockard and Papanicolaou in 1917, consists in the microscopic examination of
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| smears prepared at frequent intervals from the fluid content
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| of the vagina. The vaginal fluid usually has a mucous consistency and contains a variety of desquamated cells, as well
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| as leucocytes, lymphocytes, often erythrocytes, and a large
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| number of bacteria. As the relative number and the distribution of these elements change periodically, smears prepared
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| from such fluid show modifications in their composition and
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| structure. The successive alternation of periods of sexual
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| activity and inactivity, which characterizes the mammals,
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| imparts to the vaginal fluid a rhythmical sequence of typical
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| cellular stages which can be easily recognized.
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| These cyclic changes affect the entire genital tract, and, consequently, every change in the vaginal fluid is strictly correlated With corresponding changes in the other organs of
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| the female genital system, particularly the uterus and the ovaries. The time of ovulation may be accurately detected by this method in living mammals, while, before its application, no such information could be obtained without an operation or the sacrifice of an animal.
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| In the guinea pig, which is polyoestrous, the sexual cycles
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| return periodically throughout the year every 15 to 16 days
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| (15.73 in average). The longest part of each sexual cycle,
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| i.e., about 12 days, is occupied by a period of relative inactivity or rest, which is called ‘clioestrus.’ During this time
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| the vaginal smear, as described by Stockard and Papanicolaou ( ’l7), consists chiefly of leucocytes and a varying num-
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| ber of atypical squamous cells. The period of increased
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| sexual activity lasts 3 to 4 days and is characterized by a
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| succession of stages, which have been designated as stages
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| I, II, III, IV. During stage I the leucocytes almost disappear
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| from the smear, the secretion of mucus becomes more abundant, and the cells which dominate the smear are of a squamous type with very small pyknotic nuclei which are at times
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| fragmented. At the end of stage I there is an intermediate
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| period, characterized by the prevalence of ‘elongate, cornified
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| cells Without nuclei.’ Stage II also shows a scarcity of leucocytes and a prevalence of cells which are derived from the
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| deeper layers of the vaginal epithelial wall, being thus less de-
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| generated and having a larger nucleus and a more compact
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| form. Stage III is characterized by the reappearance of
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| myriads of leucocytes and by cells mainly of the II and III
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| type. The III cells are as a rule modified type II cells, the
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| bodies of which had been penetrated by the invading leucocytes. Stage IV is practically the same as stage III, with the
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| difference that erythrocytes are also present in the smear as
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| the result of slight bleedings.
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| These four smear stages are of short duration, succeeding one another rapidly and are strictly coordinated with corresponding stages of the uterine and ovarian cycles. During
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| stage I the ovary contains large ripening follicles and regressing corpora lutea. The uterus is congested and hypertrophied and its epithelial lining consists of high cuboidal or columnar cells. During the intermediate or cornified stage the follicles as well as the uterus reach their highest development. The onset of the catabolic processes, i.e., the bursting
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| of the ripe follicles and the denudation of the uterine mucosa,
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| is associated with the appearance of vaginal stages II and III.
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| Ovulation in the guinea pig is thus characterized by definite
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| vaginal changes and occurs at about the time of the sloughing
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| off of the uterine mucosa. Comparable conditions have been
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| found to exist in other rodents, such as the rat and the mouse.
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| Long and Evans (’22), in their monograph on the oestrous
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| cycle in the rat, described definite relations between the vaginal cycle, as revealed by vaginal smears, and the uterine and
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| ovarian cycles. The rat has normally a very short sexual
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| periodicity of about 5 days’ duration. Long and Evans recognized five smear stages: Stage 1: Leucocytes disappear;
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| great numbers of small round nucleated epithelial cells of
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| strikingly uniform appearance and size; duration 12 hours.
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| Stage 2, or ‘cornified cell stage’: leucocytes still absent;
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| appearance of cornified cells. Stage 3, or ‘late cornified cell
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| stage’: leucocytes absent; rich in cornified cells, forming
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| large cheesy masses; duration of stages 2 and 3 about 30
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| hours. Stage 4, or ‘leucocytic—cornified cell stage’: reappearance of leucocytes; gradual disappearance of the cornified
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| cells and appearance of epithelial cells; duration 6 hours.
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| Stage 5 corresponds to the dioestrus, which is of an approximate duration of 3 days and is characterized by the presence
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| of leucocytes and atypical epithelial cells in the vaginal smear.
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| The cornification of the vagina is much more pronounced
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| in the rat than in the guinea pig and this accounts for some
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| of the smear differences between these two animals. In the
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| rat the cornification extends over two well-defined stages, the
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| second and third of Long and Evans, whereas in the guinea
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| pig it is usually overlapped by the I and II to the III stages;
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| on this account, it had been originally described by Stockard
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| and Papanicolaou as an intermediate period. In the rat the
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| uterine growth is completed during the first and second
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| stages. The catabolic processes in the uterus begin during
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| the cornified cell stages, and the ovulation occurs during the last hours of this same period. The uterine epithelium is
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| vacuolized and degenerated, but an actual denudation, as in
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| the guinea pig, does not occur. The various phases of the
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| sexual cycle in the rat proceed in rapid succession, but their
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| coordination is maintained.
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| The corresponding vaginal smear stages in the guinea pig and the rat could be illustrated as follows:
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| {{Papanicolaou1933 guinea pig and rat vaginal smear table}}
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| This comparison indicates that the succession of stages is similar in both animals. Ovulation occurs at practically the same moment in relation to the above stages, i.e., at the end of the intermediate period in the guinea pig and during the last hours of the cornification period (second and third) in the rat.
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| In the mouse, Allen (’22) has also recognized five stages, the entire sexual cycle averaging about 4% days.
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| Selle (’22) has reclassified the vaginal smears of the guinea pig after a detailed study of the changes in the vaginal epithelium. He has recognized a separate ‘cornified cell stage’ similar to the same stage in the rat. Such a stage may be actually present in a large number ‘of cases, but, as a rule, it is indistinct and overlaps both the preceding and the following stages. This cornified cell stage of Selle corresponds to the ‘intermediate period’ of Stockard and Papanicolaou, and not to the stage 2 as given in Selle’s table. His stage 3 corresponds to the intermediate +II, whereas his stage 4 is equivalent to the stages III and IV of Stockard and Papanicolaou.
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| Murphey (’22) and Frei and Metzger (’26) have recognized four stages in the oestrous cycle in the cow with the vaginal smear method. Hartman (’23), in his study of the oestrous cycle in the opossum, also recognized four stages corresponding to the ones described in the rodents.
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| In 1924, McKenzie and Zupp, and in 1926, Wilson studied vaginal smears in swine. They found periodic variations in the cellular and leucocytic make-up of the smears, indicative of a cyclic rhythm.
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| A further step was made by Corner’s (’23) application of
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| this method to the Primates. His observations on Macacus
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| rhesus, though not entirely in line with the smear findings
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| in the rodents, yet revealed a rhythm in the vaginal reactions.
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| The average length of cycle in the Macacus, when the regular
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| cycles are considered, is about 27 days, which is almost the
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| same as in the human. During menstruation, which lasted
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| 4 to 6 days, the vaginal smear contained erythrocytes, epithelial cells, and leucocytes. In the first half of the intermenstrual interval there were relatively few epithelial cells and
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| many leucocytes. About the middle of the interval a sharp
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| drop in leucocytes occurred or even total disappearance.
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| Leucocytes sometimes reappeared a few days later or were
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| absent until onset of next menstruation or a few days before.
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| During the second half of the intermenstrual interval there
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| was an increased desquamation of epithelial cells. The pre-menstrual smear seemed to be thick and caseous, whereas the
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| postmenstrual smear was rather thin and scanty.
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| These observations, though not establishing a definite succession of clear-cut stages, reveal the existence of a rhythm expressed mainly in the periodical increase and decrease in the number of the leucocytes and the epithelial cells. As Corner concludes:
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| ==Plates==
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| ===Plate 9===
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| Drawings of various types of cells found in normal human vaginal smears.
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| [[File:Papanicolaou1933-plate09.jpg|600px]]
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| * '''36 to 60''' Cells from human vaginal smears at different stages of the normal menstrual cycle.
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| ===Plate 10===
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| Drawings of various types of cells found in normal human vaginal smears.
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| [[File:Papanicolaou1933-plate10.jpg|600px]]
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| * '''61 to 68''' Cells from human vaginal smears at different stagesrof the normal menstrual cycle.
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| * '''69 to 79''' Characteristic types of cells found in human vaginal smears during pregnancy.
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| * '''80''' Normal mononuclears during menstruation.
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| * '''81''' Large mononuclears found in post—partum.
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| * '''82 to 84''' Cliaraeteristic types of cells found in postpartum.
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| {{Footer}}
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| [[Category:Menstrual Cycle]]
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| [[Category:1930's]]
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